Inflammation
inflammation
Dr. Suphansa Sawamiphak
Heart failure with preserved ejection fraction (HFpEF) is commonly associated with systemic inflammation. It has been posited that disruption of immune homeostasis underlies functional and structural remodeling of the microvessels, thereby leading to diastolic dysfunctionality of the myocardium. Intervention on this pathogenic pathway is anticipated to serve as the much-needed therapeutic strategy against HFpEF. However, cellular and molecular mechanism underlying the crosstalk between the immune and cardiovascular system in HFpEF pathogenesis is yet to be uncovered. Here we set off to investigate the entwined immune-vascular-cardiac interactions. Our goal is not only to shed more light into the mechanistic insights, but also to identify potential therapeutic candidates capable of preventing adverse cardiovascular remodeling. To this end, we focus on elucidating the role of the gut and microbial metabolites in the regulation of the multi-systemic crosstalk by exploiting optical translucency and genetic tractability of the zebrafish as a disease model. We use a range of techniques in zebrafish genetics, molecular biology, advanced microscopy, and transcriptomic analysis. For more information and for applying follow this link: https://www.mdc-berlin.de/career/jobs/phd-student
Prof Wei Cao
Our laboratory studies the biology of neuroinflammation and related pathogenic events associated with neurodegenerative diseases. A leading health and economic burden to an aging society, Alzheimer’s Disease (AD) is a condition with complex etiology and manifests in dysregulated neuronal functions and intercellular communications in the brain. Increasingly, neuroinflammatory signals and microglial responses are critically implicated in AD and other neurodegenerative diseases. We are keen to illuminate the fundamental principles that govern the neuroinflammatory phenomena in driving AD and brain aging (check our recent publications J. Clin. Invest. 130:1912 (2020); Front Neurosci 14:577744 (2020); BioRiv 2021.11.01.466525(2021)). Establishing a brand new presence in Univ of Texas Health Science Center at Houston, we are looking for an enthusiastic candidate to join a spirited group. The focus of the immediate project is to elucidate the mechanisms of neuroinflammation and to identify the key pathways and factors involved in AD by examining various CNS cells and analyzing mouse disease models. Additional projects will investigate cellular elements that modify glial functions in the aging brain and/or under the context of AD pathogenesis. Other areas of our research interest include devising strategies to target AD-relevant inflammatory and pathogenic mediators.
Professor Stuart Allan
Applications are invited for the Natalie Kate Moss (NKM) Research Fellowship in Brain Haemorrhage, aimed at an outstanding scientist at an early stage in their academic career (i.e. within seven years of PhD submission). The NKM Fellow should show a high level of drive and ambition in their ideas relating to the study of brain haemorrhage. Working within the newly established Geoffrey Jefferson Brain Research Centre (www.ncaresearch.org.uk/gjbrainresearch/) the NKM Fellow will benefit from a vibrant and inspiring environment to pursue outstanding research. The NKM Fellow will be mentored and given all appropriate assistance in winning external funding and awards. The NKM Fellow will receive full-time salary for 3.5 years, £100k research support costs, immediate co-supervision of a PhD student (dependent on experience) and access to key technology platforms. The post is available from 1st February 2022. https://www.jobs.manchester.ac.uk/displayjob.aspx?isPreview=Yes&jobid=21061
Massimo Sartori
The Neuro-Mechanical Modeling and Engineering Lab (NMLab) at the University of Twente invites applications for a 3-year postdoctoral position funded by the ERC Consolidator Grant ROBOREACTOR. This is an exciting opportunity to join a cutting-edge team at the intersection of neurophysiology, biomechanics, and rehabilitation robotics. As a postdoctoral researcher in this project, you will work on breakthrough technology for non-invasive biopsies of skeletal muscles, specifically targeting the lower limbs. You will employ high-density electromyography (HD-EMG) and ultrasonography, combined with advanced statistical and machine learning techniques, to characterize muscle properties at multiple scales. Key focuses include motor unit phenotype distribution, 3D muscle fascicle morphology, and muscle inflammation levels. You will validate these non-invasive measurements against invasive biopsy samples and advanced imaging techniques, working with both healthy individuals and post-stroke survivors in the context of rehabilitation robotics and regenerative robotics technologies.
Biomolecular condensates as drivers of neuroinflammation
Rejuvenating the Alzheimer’s brain: Challenges & Opportunities
How the brain barriers ensure CNSimmune privilege”
Britta Engelhard’s research is devoted to understanding thefunction of the different brain barriers in regulating CNS immunesurveillance and how their impaired function contributes toneuroinflammatory diseases such as Multiple Sclerosis (MS) orAlzheimer’s disease (AD). Her laboratory combines expertise invascular biology, neuroimmunology and live cell imaging and hasdeveloped sophisticated in vitro and in vivo approaches to studyimmune cell interactions with the brain barriers in health andneuroinflammation.
Physical Activity, Sedentary Behaviour and Brain Health
Personalized medicine and predictive health and wellness: Adding the chemical component
Wearable sensors that detect and quantify biomarkers in retrievable biofluids (e.g., interstitial fluid, sweat, tears) provide information on human dynamic physiological and psychological states. This information can transform health and wellness by providing actionable feedback. Due to outdated and insufficiently sensitive technologies, current on-body sensing systems have capabilities limited to pH, and a few high-concentration electrolytes, metabolites, and nutrients. As such, wearable sensing systems cannot detect key low-concentration biomarkers indicative of stress, inflammation, metabolic, and reproductive status. We are revolutionizing sensing. Our electronic biosensors detect virtually any signaling molecule or metabolite at ultra-low levels. We have monitored serotonin, dopamine, cortisol, phenylalanine, estradiol, progesterone, and glucose in blood, sweat, interstitial fluid, and tears. The sensors are based on modern nanoscale semiconductor transistors that are straightforwardly scalable for manufacturing. We are developing sensors for >40 biomarkers for personalized continuous monitoring (e.g., smartwatch, wearable patch) that will provide feedback for treating chronic health conditions (e.g., perimenopause, stress disorders, phenylketonuria). Moreover, our sensors will enable female fertility monitoring and the adoption of more healthy lifestyles to prevent disease and improve physical and cognitive performance.
How are the epileptogenesis clocks ticking?
The epileptogenesis process is associated with large-scale changes in gene expression, which contribute to the remodelling of brain networks permanently altering excitability. About 80% of the protein coding genes are under the influence of the circadian rhythms. These are 24-hour endogenous rhythms that determine a large number of daily changes in physiology and behavior in our bodies. In the brain, the master clock regulates a large number of pathways that are important during epileptogenesis and established-epilepsy, such as neurotransmission, synaptic homeostasis, inflammation, blood-brain barrier among others. In-depth mapping of the molecular basis of circadian timing in the brain is key for a complete understanding of the cellular and molecular events connecting genes to phenotypes.
Blood-brain barrier dysfunction in epilepsy: Time for translation
The neurovascular unit (NVU) consists of cerebral blood vessels, neurons, astrocytes, microglia, and pericytes. It plays a vital role in regulating blood flow and ensuring the proper functioning of neural circuits. Among other, this is made possible by the blood-brain barrier (BBB), which acts as both a physical and functional barrier. Previous studies have shown that dysfunction of the BBB is common in most neurological disorders and is associated with neural dysfunction. Our studies have demonstrated that BBB dysfunction results in the transformation of astrocytes through transforming growth factor beta (TGFβ) signaling. This leads to activation of the innate neuroinflammatory system, changes in the extracellular matrix, and pathological plasticity. These changes ultimately result in dysfunction of the cortical circuit, lower seizure threshold, and spontaneous seizures. Blocking TGFβ signaling and its associated pro-inflammatory pathway can prevent this cascade of events, reduces neuroinflammation, repairs BBB dysfunction, and prevents post-injury epilepsy, as shown in experimental rodents. To further understand and assess BBB integrity in human epilepsy, we developed a novel imaging technique that quantitatively measures BBB permeability. Our findings have confirmed that BBB dysfunction is common in patients with drug-resistant epilepsy and can assist in identifying the ictal-onset zone prior to surgery. Current clinical studies are ongoing to explore the potential of targeting BBB dysfunction as a novel treatment approach and investigate its role in drug resistance, the spread of seizures, and comorbidities associated with epilepsy.
Astrocyte reprogramming / activation and brain homeostasis
Astrocytes are multifunctional glial cells, implicated in neurogenesis and synaptogenesis, supporting and fine-tuning neuronal activity and maintaining brain homeostasis by controlling blood-brain barrier permeability. During the last years a number of studies have shown that astrocytes can also be converted into neurons if they force-express neurogenic transcription factors or miRNAs. Direct astrocytic reprogramming to induced-neurons (iNs) is a powerful approach for manipulating cell fate, as it takes advantage of the intrinsic neural stem cell (NSC) potential of brain resident reactive astrocytes. To this end, astrocytic cell fate conversion to iNs has been well-established in vitro and in vivo using combinations of transcription factors (TFs) or chemical cocktails. Challenging the expression of lineage-specific TFs is accompanied by changes in the expression of miRNAs, that post-transcriptionally modulate high numbers of neurogenesis-promoting factors and have therefore been introduced, supplementary or alternatively to TFs, to instruct direct neuronal reprogramming. The neurogenic miRNA miR-124 has been employed in direct reprogramming protocols supplementary to neurogenic TFs and other miRNAs to enhance direct neurogenic conversion by suppressing multiple non-neuronal targets. In our group we aimed to investigate whether miR-124 is sufficient to drive direct reprogramming of astrocytes to induced-neurons (iNs) on its own both in vitro and in vivo and elucidate its independent mechanism of reprogramming action. Our in vitro data indicate that miR-124 is a potent driver of the reprogramming switch of astrocytes towards an immature neuronal fate. Elucidation of the molecular pathways being triggered by miR-124 by RNA-seq analysis revealed that miR-124 is sufficient to instruct reprogramming of cortical astrocytes to immature induced-neurons (iNs) in vitro by down-regulating genes with important regulatory roles in astrocytic function. Among these, the RNA binding protein Zfp36l1, implicated in ARE-mediated mRNA decay, was found to be a direct target of miR-124, that be its turn targets neuronal-specific proteins participating in cortical development, which get de-repressed in miR-124-iNs. Furthermore, miR-124 is potent to guide direct neuronal reprogramming of reactive astrocytes to iNs of cortical identity following cortical trauma, a novel finding confirming its robust reprogramming action within the cortical microenvironment under neuroinflammatory conditions. In parallel to their reprogramming properties, astrocytes also participate in the maintenance of blood-brain barrier integrity, which ensures the physiological functioning of the central nervous system and gets affected contributing to the pathology of several neurodegenerative diseases. To study in real time the dynamic physical interactions of astrocytes with brain vasculature under homeostatic and pathological conditions, we performed 2-photon brain intravital imaging in a mouse model of systemic neuroinflammation, known to trigger astrogliosis and microgliosis and to evoke changes in astrocytic contact with brain vasculature. Our in vivo findings indicate that following neuroinflammation the endfeet of activated perivascular astrocytes lose their close proximity and physiological cross-talk with vasculature, however this event is at compensated by the cross-talk of astrocytes with activated microglia, safeguarding blood vessel coverage and maintenance of blood-brain integrity.
IL1beta+ macrophages fuel pathogenic inflammation in pancreatic cancer
Neuroinflammation in Epilepsy: what have we learned from human brain tissue specimens ?
Epileptogenesis is a gradual and dynamic process leading to difficult-to-treat seizures. Several cellular, molecular, and pathophysiologic mechanisms, including the activation of inflammatory processes. The use of human brain tissue represents a crucial strategy to advance our understanding of the underlying neuropathology and the molecular and cellular basis of epilepsy and related cognitive and behavioral comorbidities, The mounting evidence obtained during the past decade has emphasized the critical role of inflammation in the pathophysiological processes implicated in a large spectrum of genetic and acquired forms of focal epilepsies. Dissecting the cellular and molecular mediators of the pathological immune responses and their convergent and divergent mechanisms, is a major requisite for delineating their role in the establishment of epileptogenic networks. The role of small regulatory molecules involved in the regulation of specific pro- and anti-inflammatory pathways and the crosstalk between neuroinflammation and oxidative stress will be addressed. The observations supporting the activation of both innate and adaptive immune responses in human focal epilepsy will be discussed and elaborated, highlighting specific inflammatory pathways as potential targets for antiepileptic, disease-modifying therapeutic strategies.
The role of CNS microglia in health and disease
Microglia are the resident CNS macrophages of the brain parenchyma. They have many and opposing roles in health and disease, ranging from inflammatory to anti-inflammatory and protective functions, depending on the developmental stage and the disease context. In Multiple Sclerosis, microglia are involved to important hallmarks of the disease, such as inflammation, demyelination, axonal damage and remyelination, however the exact mechanisms controlling their transformation towards a protective or devastating phenotype during the disease progression remains largely unknown until now. We wish to understand how brain microglia respond to demyelinating insults and how their behaviour changes in recovery. To do so we developed a novel histopathological analysis approach in 3D and a cell-based analysis tool that when applied in the cuprizone model of demyelination revealed region- and disease- dependent changes in microglial dynamics in the brain grey matter during demyelination and remyelination. We now use similar approaches with the aim to unravel sensitive changes in microglial dynamics during neuroinflammation in the EAE model. Furthermore, we employ constitutive knockout and tamoxifen-inducible gene-targeting approaches, immunological techniques, genetics and bioinformatics and currently seek to clarify the specific role of the brain resident microglial NF-κB molecular pathway versus other tissue macrophages in EAE.
Mechanisms Underlying the Persistence of Cancer-Related Fatigue
Cancer-related fatigue is a prominent and debilitating side effect of cancer and its treatment. It can develop prior to diagnosis, generally peaks during cancer treatment, and can persist long after treatment completion. Its mechanisms are multifactorial, and its expression is highly variable. Unfortunately, treatment options are limited. Our research uses syngeneic murine models of cancer and cisplatin-based chemotherapy to better understand these mechanisms. Our data indicate that both peripherally and centrally processes may contribute to the developmental of fatigue. These processes include metabolic alterations, mitochondrial dysfunction, pre-cachexia, and inflammation. However, our data has revealed that behavioral fatigue can persist even after the toxicity associated with cancer and its treatment recover. For example, running during cancer treatment attenuates kidney toxicity while also delaying recovery from fatigue-like behavior. Additionally, administration of anesthetics known to disrupt memory consolidation at the time treatment can promote recovery, and treatment-related cues can re-instate fatigue after recovery. Cancer-related fatigue can also promote habitual behavioral patterns, as observed using a devaluation task. We interpret this data to suggest that limit metabolic resources during cancer promote the utilization of habit-based behavioral strategies that serve to maintain fatigue behavior into survivorship. This line of work is exciting as it points us toward novel interventional targets for the treatment of persistent cancer-related fatigue.
Valentine’s Day for people with multiple sclerosis: promoting brain repair through remyelination
Current disease-modifying therapies in multiple sclerosis are all focused on suppressing the inflammatory phase of the disease. This has been extremely successful, and it is doubtful that significantly more efficacious anti-inflammatory treatments will be found. However, it remains the case that people with relapsing-remitting multiple sclerosis acquire disability on treatment, and enter the secondary progressive phase. I argue that we now need treatments that prevent neuronal degeneration. The most promising approach is to prevent axons degenerating by remyelination. Since the discovery that the adult brain contains stem cells which can remyelinate, the problem now is how to promote endogenous remyelination, and how to know when we have achieved this! We have successfully identified one drug which promotes remyelination but unfortunately it is too toxic for use in the clinic. So the hunt continues.
Inflammation and Pregancy
Talk(1): Fetal and maternal NLRP3 signaling is required for preterm labor and birth. (DOI: 10.1172/jci.insight.158238) Talk(2): Maternal IL-33 critically regulates tissue remodeling and type 2 immune responses in the uterus during early pregnancy in mice (DOI: 10.1073/pnas.2123267119)
Early life adversity, inflammation, and depression-onset: Results from the Teen Resilience Project
My research focuses broadly on the lifelong health disparities associated with experiences of adversity early in life. In this talk I will present the results of our recently completed Teen Resilience Project, a prospective and longitudinal study of first onset depression during adolescence. First, I will present the results on whether and how inflammatory processes may be shaped by early life adversity. Second, I will present data on the role of stress-induced inflammation in reward-related psychological processes. Finally, I will discuss the biobehavioral predictors of first-onset depression in this sample.
Redox and mitochondrial dysregulation in epilepsy
Epileptic seizures render the brain uniquely dependent on energy producing pathways. Studies in our laboratory have been focused on the role of redox processes and mitochondria in the context of abnormal neuronal excitability associated with epilepsy. We have shown that that status epilepticus (SE) alters mitochondrial and cellular redox status, energetics and function and conversely, that reactive oxygen species and resultant dysfunction can lead to chronic epilepsy. Oxidative stress and neuroinflammatory pathways have considerable crosstalk and targeting redox processes has recently been shown to control neuroinflammation and excitability. Understanding the role of metabolic and redox processes can enable the development of novel therapeutics to control epilepsy and/or its comorbidities.
Pro-regenerative functions of microglia in demyelinating diseases
Our goal is to understand why myelin repair fails in multiple sclerosis and to develop regenerative medicines for the nervous system. A central obstacle for progress in this area has been the complex biology underlying the response to CNS injury. Acute CNS damage is followed by a multicellular response that encompasses different cell types and spans different scales. Currently, we do not understand which factors determines lesion recovery. Failure of inflammation to resolve is a key underlying reason of poor regeneration, and one focus is therefore on the biology of microglia during de- and remyelination, and their cross talk to other cells, in particular oligodendrocytes and the progenitor cells. In addition, we are exploring the link between lipid metabolism and inflammation, and its role in the regulation of regeneration. I will report about our recent progress in our understanding of how microglia promote regeneration in the CNS.
PET imaging in brain diseases
Talk 1. PET based biomarkers of treatment efficacy in temporal lobe epilepsy A critical aspect of drug development involves identifying robust biomarkers of treatment response for use as surrogate endpoints in clinical trials. However, these biomarkers also have the capacity to inform mechanisms of disease pathogenesis and therapeutic efficacy. In this webinar, Dr Bianca Jupp will report on a series of studies using the GABAA PET ligand, [18F]-Flumazenil, to establish biomarkers of treatment response to a novel therapeutic for temporal lobe epilepsy, identifying affinity at this receptor as a key predictor of treatment outcome. Dr Bianca Jupp is a Research Fellow in the Department of Neuroscience, Monash University and Lead PET/CT Scientist at the Alfred Research Alliance–Monash Biomedical Imaging facility. Her research focuses on neuroimaging and its capacity to inform the neurobiology underlying neurological and neuropsychiatric disorders. Talk 2. The development of a PET radiotracer for reparative microglia Imaging of neuroinflammation is currently hindered by the technical limitations associated with TSPO imaging. In this webinar, Dr Lucy Vivash will discuss the development of PET radiotracers that specifically image reparative microglia through targeting the receptor kinase MerTK. This includes medicinal chemistry design and testing, radiochemistry, and in vitro and in vivo testing of lead tracers. Dr Lucy Vivash is a Research Fellow in the Department of Neuroscience, Monash University. Her research focuses on the preclinical development and clinical translation of novel PET radiotracers for the imaging of neurodegenerative diseases.
MBI Webinar on preclinical research into brain tumours and neurodegenerative disorders
WEBINAR 1 Breaking the barrier: Using focused ultrasound for the development of targeted therapies for brain tumours presented by Dr Ekaterina (Caty) Salimova, Monash Biomedical Imaging Glioblastoma multiforme (GBM) - brain cancer - is aggressive and difficult to treat as systemic therapies are hindered by the blood-brain barrier (BBB). Focused ultrasound (FUS) - a non-invasive technique that can induce targeted temporary disruption of the BBB – is a promising tool to improve GBM treatments. In this webinar, Dr Ekaterina Salimova will discuss the MRI-guided FUS modality at MBI and her research to develop novel targeted therapies for brain tumours. Dr Ekaterina (Caty) Salimova is a Research Fellow in the Preclinical Team at Monash Biomedical Imaging. Her research interests include imaging cardiovascular disease and MRI-guided focused ultrasound for investigating new therapeutic targets in neuro-oncology. - WEBINAR 2 Disposition of the Kv1.3 inhibitory peptide HsTX1[R14A], a novel attenuator of neuroinflammation presented by Sanjeevini Babu Reddiar, Monash Institute of Pharmaceutical Sciences The voltage-gated potassium channel (Kv1.3) in microglia regulates membrane potential and pro-inflammatory functions, and non-selective blockade of Kv1.3 has shown anti-inflammatory and disease improvement in animal models of Alzheimer’s and Parkinson’s diseases. Therefore, specific inhibitors of pro-inflammatory microglial processes with CNS bioavailability are urgently needed, as disease-modifying treatments for neurodegenerative disorders are lacking. In this webinar, PhD candidate Ms Sanju Reddiar will discuss the synthesis and biodistribution of a Kv1.3-inhibitory peptide using a [64Cu]Cu-DOTA labelled conjugate. Sanjeevini Babu Reddiar is a PhD student at the Monash Institute of Pharmaceutical Sciences. She is working on a project identifying the factors governing the brain disposition and blood-brain barrier permeability of a Kv1.3-blocking peptide.
JAK/STAT regulation of the transcriptomic response during epileptogenesis
Temporal lobe epilepsy (TLE) is a progressive disorder mediated by pathological changes in molecular cascades and neural circuit remodeling in the hippocampus resulting in increased susceptibility to spontaneous seizures and cognitive dysfunction. Targeting these cascades could prevent or reverse symptom progression and has the potential to provide viable disease-modifying treatments that could reduce the portion of TLE patients (>30%) not responsive to current medical therapies. Changes in GABA(A) receptor subunit expression have been implicated in the pathogenesis of TLE, and the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway has been shown to be a key regulator of these changes. The JAK/STAT pathway is known to be involved in inflammation and immunity, and to be critical for neuronal functions such as synaptic plasticity and synaptogenesis. Our laboratories have shown that a STAT3 inhibitor, WP1066, could greatly reduce the number of spontaneous recurrent seizures (SRS) in an animal model of pilocarpine-induced status epilepticus (SE). This suggests promise for JAK/STAT inhibitors as disease-modifying therapies, however, the potential adverse effects of systemic or global CNS pathway inhibition limits their use. Development of more targeted therapeutics will require a detailed understanding of JAK/STAT-induced epileptogenic responses in different cell types. To this end, we have developed a new transgenic line where dimer-dependent STAT3 signaling is functionally knocked out (fKO) by tamoxifen-induced Cre expression specifically in forebrain excitatory neurons (eNs) via the Calcium/Calmodulin Dependent Protein Kinase II alpha (CamK2a) promoter. Most recently, we have demonstrated that STAT3 KO in excitatory neurons (eNSTAT3fKO) markedly reduces the progression of epilepsy (SRS frequency) in the intrahippocampal kainate (IHKA) TLE model and protects mice from kainic acid (KA)-induced memory deficits as assessed by Contextual Fear Conditioning. Using data from bulk hippocampal tissue RNA-sequencing, we further discovered a transcriptomic signature for the IHKA model that contains a substantial number of genes, particularly in synaptic plasticity and inflammatory gene networks, that are down-regulated after KA-induced SE in wild-type but not eNSTAT3fKO mice. Finally, we will review data from other models of brain injury that lead to epilepsy, such as TBI, that implicate activation of the JAK/STAT pathway that may contribute to epilepsy development.
Identification and treatment of advanced, rupture-prone plaques to reduce cardiovascular mortality
Atherosclerosis is the underlying cause of major cardiovascular events, including heart attack and stroke. The build-up of plaque in coronary arteries can be a major risk for events, but risk is significantly higher in patients with vulnerable rather than stable plaque. Diagnostic imaging of vulnerable plaque is extremely useful for both stratifying patient risk and for determining effectiveness of experimental intervention in reducing cardiovascular risk. In the preclinical setting, being able to distinguish between stable and vulnerable plaque development and pair this with biochemical measures is critical for identification of new experimental candidates. In this webinar, Professor Stephen Nicholls and Dr Kristen Bubb from the Victorian Heart Institute will discuss the benefits of being able to visualise vulnerable plaque for both clinical and preclinical research. Professor Stephen Nicholls is a clinician-researcher and the Head of the Victorian Heart Institute. He is the lead investigator on multiple large, international, cardiovascular outcomes trials. He has attracted over $100 million in direct research funding and published more than 400 peer-reviewed manuscripts. He is focused on both therapeutic intervention to reduce vascular inflammation and lipid accumulation and precision medicine approaches to prevent cardiovascular mortality. Dr Kristen Bubb is a biomedical researcher and Group Leader within the Monash Biomedicine Discovery Institute Cardiovascular Program and Victorian Heart Institute. She focuses on preclinical/translational research into mechanisms underlying vascular pathologies including atherosclerosis and endothelium-driven hypertension within specific vascular systems, including pulmonary and pregnancy-induced. She has published >30 high impact papers in leading cardiovascular journals and attracted category 1&2 funding of >$750,000.
From aura to neuroinflammation: Has imaging resolved the puzzle of migraine pathophysiology?
In this talk I will present data from imaging studies that we have been conducting for the past 20 years trying to shed light on migraine physiopathology, from anatomical and functional MRI to positron emission tomography.
From Vulnerable Plaque to Vulnerable Brain: Understanding the Role of Inflammation in Vascular Health, Stroke, and Cerebrovascular Disease
Every year around 100,000 people in the UK will have a stroke. Stroke is a leading cause of adult disability, and cerebrovascular disease more broadly is a major cause of dementia. Understanding these diseases – both acute and chronic manifestations of cerebrovascular disease – requires consideration not only of the brain itself, but also the blood vessels supplying it. Atherosclerosis – the hardening of arteries as we age – may predispose to stroke by triggering the formation of blood clots that block the blood supply to the brain, but also involves inflammation that may cause chronic damage to the brain and prime both the brain and body for injury. Understanding this interaction between systemic disease and brain health may have important implications for our understanding of healthy ageing and provide novel therapeutic approaches for reducing the burden of cerebrovascular disease. This talk will consider how advances in imaging may facilitate our understanding of the processes underlying atherosclerosis and how it affects the brain in stroke, as well as work currently underway to translate this understanding into improving treatments for stroke.
How much gut needs the brain ? Gut microbiota-immune crosstalk in neuroinflammation
Neuroinflammation in epilepsy: cell type specific roles and pathophysiological outcomes
Tapeworm larvae in the brain: cellular mechanisms of epilepsy in neurocysticercosis
Cerebral infection by the larvae of the cestode, Taenia solium (neurocysticercosis), is thought to be the leading cause of adult-acquired epilepsy worldwide. Despite this, little is known about the cellular mechanisms that underlie seizure development in this condition. In this talk I will present our recent data exploring multiple interactions between cestode larvae, neuroinflammatory processes and network excitability. We find that viable cestode larvae are able to strongly suppress microglial activation and inflammatory cytokine release with consequences for the modulation host neuroinflammatory responses and seizure development in vivo. At the same time, larvae produce and release glutamate, with acute excitatory effects on neuronal circuits. We hope that an improved understanding of epileptogenic mechanisms in neurocysticercosis will one day improve the management of this condition as well as other inflammatory causes of epilepsy.
Migraine Headache: the revolution and its evolution
This seminar will focus on the extraordinary shift in migraine research during the last 4 decades with the discovery of the trigeminovascular system (TVS) and it’s major impact on pathophysiology and treatment. Compelling evidence supporting the importance of TVS, cortical spreading depression and parameningeal inflammation will be explored as will the implications of newly discovered microvascular channels within the meninges on an attack.
Exploring and targeting CNS inflammation in brain metastases
The role of the complement pathway in post-traumatic sleep disruption and epilepsy
While traumatic brain injury (TBI) acutely disrupts the cortex, most TBI-related disabilities reflect secondary injuries that accrue over time. The thalamus is a likely site of secondary damage because of its reciprocal connections with the cortex. Using a mouse model of mild cortical injury that does not directly damage subcortical structures (mTBI), we found a chronic increase in C1q expression specifically in the corticothalamic circuit. Increased C1q expression co-localized with neuron loss and chronic inflammation, and correlated with disruption in sleep spindles and emergence of epileptic activities. Blocking C1q counteracted these outcomes, suggesting that C1q is a disease modifier in mTBI. Single-nucleus RNA sequencing demonstrated that microglia are the source of thalamic C1q. Since the corticothalamic circuit is important for cognition and sleep, which can be impaired by TBI, this circuit could be a new target for treating TBI-related disabilities
Regenerative Neuroimmunology - a stem cell perspective
There are currently no approved therapies to slow down the accumulation of neurological disability that occurs independently of relapses in multiple sclerosis (MS). International agencies are engaging to expedite the development of novel strategies capable of modifying disease progression, abrogating persistent CNS inflammation, and support degenerating axons in people with progressive MS. Understanding why regeneration fails in the progressive MS brain and developing new regenerative approaches is a key priority for the Pluchino Lab. In particular, we aim to elucidate how the immune system, in particular its cells called myeloid cells, affects brain structure and function under normal healthy conditions and in disease. Our objective is to find how myeloid cells communicate with the central nervous system and affect tissue healing and functional recovery by stimulating mechanisms of brain plasticity mechanisms such as the generation of new nerve cells and the reduction of scar formation. Applying combination of state-of-the-art omic technologies, and molecular approaches to study murine and human disease models of inflammation and neurodegeneration, we aim to develop experimental molecular medicines, including those with stem cells and gene therapy vectors, which slow down the accumulation of irreversible disabilities and improve functional recovery after progressive multiple sclerosis, stroke and traumatic injuries. By understanding the mechanisms of intercellular (neuro-immune) signalling, diseases of the brain and spinal cord may be treated more effectively, and significant neuroprotection may be achieved with new tailored molecular therapeutics.
Innate immune response in brain pathologies: Lost in translation?
Inflammation is a key component of the innate immune response. Primarily designed to remove noxious agents and limit their detrimental effects, the prolonged and/or inappropriately scaled innate immune response may be detrimental to the host and lead to a chronic disease. Indeed, there is increasing evidence suggesting that a chronic deregulation of immunity may represent one of the key elements in the pathobiology of many brain disorders. Microglia are the principal immune cells of the brain. The consensus today is that once activated microglia/macrophages can acquire a wide repertoire of profiles ranging from the classical pro-inflammatory to alternative and protective phenotypes. Recently, we described a novel ribosome-based regulatory mechanism/checkpoint that controls innate immune gene translation and microglial activation involving RNA binding protein SRSF3. Here we will discuss the implications of SRSF3 and other endogenous immune regulators in deregulation of immunity observed in different models of brain pathologies. Furthermore, we will discuss whether targeting SRSF3 and mRNA translation may open novel avenues for therapeutic modulation of immune response in the brain.
Towards targeted therapies for the treatment of Dravet Syndrome
Dravet syndrome is a severe epileptic encephalopathy that begins during the first year of life and leads to severe cognitive and social interaction deficits. It is mostly caused by heterozygous loss-of-function mutations in the SCN1A gene, which encodes for the alpha-subunit of the voltage-gated sodium channel (Nav1.1) and is responsible mainly of GABAergic interneuron excitability. While different therapies based on the upregulation of the healthy allele of the gene are being developed, the dynamics of reversibility of the pathology are still unclear. In fact, whether and to which extent the pathology is reversible after symptom onset and if it is sufficient to ensure physiological levels of Scn1a during a specific critical period of time are open questions in the field and their answers are required for proper development of effective therapies. We generated a novel Scn1a conditional knock-in mouse model (Scn1aSTOP) in which the endogenous Scn1a gene is silenced by the insertion of a floxed STOP cassette in an intron of Scn1a gene; upon Cre recombinase expression, the STOP cassette is removed, and the mutant allele can be reconstituted as a functional Scn1a allele. In this model we can reactivate the expression of Scn1a exactly in the neuronal subtypes in which it is expressed and at its physiological level. Those aspects are crucial to obtain a final answer on the reversibility of DS after symptom onset. We exploited this model to demonstrate that global brain re-expression of the Scn1a gene when symptoms are already developed (P30) led to a complete rescue of both spontaneous and thermic inducible seizures and amelioration of behavioral abnormalities characteristic of this model. We also highlighted dramatic gene expression alterations associated with astrogliosis and inflammation that, accordingly, were rescued by Scn1a gene expression normalization at P30. Moreover, employing a conditional knock-out mouse model of DS we reported that ensuring physiological levels of Scn1a during the critical period of symptom appearance (until P30) is not sufficient to prevent the DS, conversely, mice start to die of SUDEP and develop spontaneous seizures. These results offer promising insights in the reversibility of DS and can help to accelerate therapeutic translation, providing important information on the timing for gene therapy delivery to Dravet patients.
Covid And Cognition
ONS figures suggest that at least 10% of individuals suffering COVID -19 Infection continue to experience several weeks after testing positive, and other studies report the proportions as even higher (e.g. Logue et al., 2021). One of the most prevalent reported symptoms among these “Long Covid” sufferers is cognitive dysfunction (Davis et al., 2020). However, to date the cognitive sequelae of COVID -19 are little understood. There are a number of reasons why COVID -19 infection might be associated with cognitive impairment and mental illness (e.g. Bougakov et al., 2020). In particular, increasing evidence indicates inflammation (e.g. Huang et al., 2020) and dysfunctional clotting (e.g. Taquet et al., 2021) as issues of major concern, both of which have been previously linked to a range of cognitive deficits (e.g. Vintimilla et al., 2019; Cumming et al., 2013). Indeed, evidence is beginning to emerge that cognitive issues may be widespread in the post-infection period, particularly among hospitalised and ventilated patients (e.g. Hampshire et al., 2020; Alemanno et al,. 2020). Here I shall present “Hot off the [SPSS]Press” results from a study on memory and cognition following COVID infection in a non-hospitalized cohort.
Associations between brain interoceptive network dysconnectivity and heightened peripheral inflammation in depression
Are the immune system, brain, mind and mood related? Could this explain why chronic low-grade peripheral inflammation is also noted in approximately 1/3 of those with major depressive disorder (MDD)? The field recognized today as immunopsychiatry was founded on scientific evidence that germinated over 30 years ago. Since, it has been understood that (i) there could be a causal link between inflammation and depression, (ii) select blood immune markers show robust potential as biomarkers for inflammation-linked depression, and more generally, (iii) Descartes' theories on mind-body dualism were biologically erroneous. Nonetheless, the mechanistic brain-immune axis in the trinity formulating inflammation-linked depression i.e. psycho-neuro-immunology, still remains unclear. This talk will discuss findings from our recent investigation endeavored to unpack this by linking functional connectivity abnormalities with peripheral immune markers.
Role of Oxytocin in regulating microglia functions to prevent brain damage of the developing brain
Every year, 30 million infants worldwide are delivered after intra-uterine growth restriction (IUGR) and 15 million are born preterm. These two conditions are the leading causes of ante/perinatal stress and brain injury responsible for neurocognitive and behavioral disorders in more than 9 million children each year. Both prematurity and IUGR are associated with perinatal systemic inflammation, a key factor associated with neuroinflammation and identified to be the best predictor of subsequent neurological impairments. Most of pharmacological candidates have failed to demonstrate any beneficial effect to prevent perinatal brain damage. In contrast, environmental enrichment based on developmental care, skin-to-skin contact and vocal/music intervention appears to confer positive effects on brain structure and function. However, mechanisms underlying these effects remain unknown. There is strong evidence that an adverse environment during pregnancy and the perinatal period can influence hormonal responses of the newborn with long-lasting neurobehavioral consequences in infancy and adulthood. Excessive cortisol release in response to perinatal stress induces pro-inflammatory and brain-programming effects. These deleterious effects are known to be balanced by Oxytocin (OT), a neuropeptide playing a key role during the perinatal period and parturition, in social behavior and regulating the central inflammatory response to injury in the adult brain. Using a rodent model of IUGR associated with perinatal brain damage, we recently reported that Carbetocin, a brain permeable long-lasting OT receptor (OTR) agonist, was associated with a significant reduction of activated microglia, the primary immune cells of the brain. Moreover this reduced microglia reactivity was associated to a long-term neuroprotection. These findings make OT a promising candidate for neonatal neuroprotection through neuroinflammation regulation. However, the causality between the endogenous OT and central inflammation response to injury has not been established and will be further studied by the lab.
What about antibiotics for the treatment of the dyskinesia induced by L-DOPA?
L-DOPA-induced dyskinesia is a debilitating adverse effect of treating Parkinson’s disease with this drug. New therapeutic approaches that prevent or attenuate this side effect is clearly needed. Wistar adult male rats submitted to 6-hydroxydopamine-induced unilateral medial forebrain bundle lesions were treated with L-DOPA (oral or subcutaneous, 20 mg kg-1) once a day for 14 days. After this period, we tested if doxycycline (40 mg kg-1, intraperitoneal, a subantimicrobial dose) and COL-3 (50 and 100 nmol, intracerebroventricular) could reverse LID. In an additional experiment, doxycycline was also administered repeatedly with L-DOPA to verify if it would prevent LID development. A single injection of doxycycline or COL-3 together with L-DOPA attenuated the dyskinesia. Co-treatment with doxycycline from the first day of L-DOPA suppressed the onset of dyskinesia. The improved motor responses to L-DOPA remained intact in the presence of doxycycline or COL-3, indicating the preservation of L-DOPA-produced benefits. Doxycycline treatment was associated with decreased immunoreactivity of FosB, cyclooxygenase-2, the astroglial protein GFAP and the microglial protein OX-42 which are elevated in the basal ganglia of rats exhibiting dyskinesia. Doxycycline also decreased metalloproteinase-2/-9 activity, metalloproteinase-3 expression and reactive oxygen species production. Metalloproteinase-2/-9 activity and production of reactive oxygen species in the basal ganglia of dyskinetic rats showed a significant correlation with the intensity of dyskinesia. The present study demonstrates the anti-dyskinetic potential of doxycycline and its analog compound COL-3 in hemiparkinsonian rats. Given the long-established and safe clinical use of doxycycline, this study suggests that these drugs might be tested to reduce or to prevent L-DOPA-induced dyskinesia in Parkinson’s patients.
Phospholipid regulation in cognitive impairment and vascular dementia
An imbalance in lipid metabolism in neurodegeneration is still poorly understood. Phospholipids (PLs) have multifactorial participation in vascular dementia as Alzheimer, post-stroke dementia, CADASIL between others. Which include the hyperactivation of phospholipases, mitochondrial stress, peroxisomal dysfunction and irregular fatty acid composition triggering proinflammation in a very early stage of cognitive impairment. The reestablishment of physiological conditions of cholesterol, sphingolipids, phospholipids and others are an interesting therapeutic target to reduce the progression of AD. We propose the positive effect of BACE1 silencing produces a balance of phospholipid profile in desaturase enzymes-depending mode to reduce the inflammation response, and recover the cognitive function in an Alzheimer´s animal and brain stroke models. Pointing out there is a great need for new well-designed research focused in preventing phospholipids imbalance, and their consequent energy metabolism impairment, pro-inflammation and enzymatic over-processing, which would help to prevent unhealthy aging and AD progression.
Sexual dimorphism of microglia
Sex differences in brain structure and function are of substantial scientific interest because of sex-related susceptibility to psychiatric and neurological disorders. Neuroinflammation is a common denominator of many of these diseases and thus microglia as the brain´s immunocompetent and instrumental cells has come into focus in sex specific studies. We and others show that male microglia are more frequent in specific brain areas and appear to have a higher potential to respond to stimuli, whereas female microglia seem to acquire a more “protective” phenotype.
Neurocircuits in control of integrative physiology
This open colloquia session is part of the special workshop entitled "Obesity at the Interface of Neuroscience and Physiology II". Abstract: Proopiomelanocortin (POMC)- and agouti related peptide (AgRP)-expressing neurons in the arcuate nucleus of the hypothalamus (ARH) are critical regulators of food intake and energy homeostasis. They rapidly integrate the energy state of the organism through sensing fuel availability via hormones, nutrient components and even rapidly upon sensory food perception. Importantly, they not only regulate feeding responses, but numerous autonomic responses including glucose and lipid metabolism, inflammation and blood pressure. More recently, we could demonstrate that sensory food cue-dependent regulation of POMC neurons primes the hepatic endoplasmic reticulum (ER) stress response to prime liver metabolism for the postpramndial state. The presentation will focus on the regulation of these neurons in control of integrative physiology, the identification of distinct neuronal circuitries targeted by these cells and finally on the broad range implications resulting from dysregulation of these circuits as a consequence of altered maternal metabolism.
Microglia function and dysfunction in Alzheimer’s disease
Emerging genetic studies of late-onset Alzheimer’s Disease implicate the brain’s resident macrophages in the pathogenesis of AD. More than half the risk genes associated with late-onset AD are selectively expressed in microglia and peripheral myeloid cells; yet we know little about the underlying biology or how myeloid cells contribute to AD pathogenesis. Using single-cell RNA sequencing and spatial transcriptomics we identified molecular signatures that can be used to localize and monitor distinct microglia functional states in the human and mouse brain. Our results show that microglia assume diverse functional states in development, aging and injury, including populations corresponding to known microglial functions including proliferation, migration, inflammation, and synaptic phagocytosis. We identified several innate immune pathways by which microglia recognize and prune synapses during development and in models of Alzheimer’s disease, including the classical complement cascade. Illuminating the mechanisms by which developing synaptic circuits are sculpted is providing important insight on understanding how to protect synapses in Alzheimer’s and other neurodegenerative diseases of synaptic dysfunction.
Sparks, flames, and inferno: epileptogenesis in the glioblastoma microenvironment
Glioblastoma cells trigger pharmacoresistant seizures that may promote tumor growth and diminish the quality of remaining life. To define the relationship between growth of glial tumors and their neuronal microenvironment, and to identify genomic biomarkers and mechanisms that may point to better prognosis and treatment of drug resistant epilepsy in brain cancer, we are analyzing a new generation of genetically defined CRISPR/in utero electroporation inborn glioblastoma (GBM) tumor models engineered in mice. The molecular pathophysiology of glioblastoma cells and surrounding neurons and untransformed astrocytes are compared at serial stages of tumor development. Initial studies reveal that epileptiform EEG spiking is a very early and reliable preclinical signature of GBM expansion in these mice, followed by rapidly progressive seizures and death within weeks. FACS-sorted transcriptomic analysis of cortical astrocytes reveals the expansion of a subgroup enriched in pro-synaptogenic genes that may drive hyperexcitability, a novel mechanism of epileptogenesis. Using a prototypical GBM IUE model, we systematically define and correlate the earliest appearance of cortical hyperexcitability with progressive cortical tumor cell invasion, including spontaneous episodes of spreading cortical depolarization, innate inflammation, and xCT upregulation in the peritumoral microenvironment. Blocking this glutamate exporter reduces seizure load. We show that the host genome contributes to seizure risk by generating tumors in a monogenic deletion strain (MapT/tau -/-) that raises cortical seizure threshold. We also show that the tumor variant profile determines epilepsy risk. Our genetic dissection approach sets the stage to broadly explore the developmental biology of personalized tumor/host interactions in mice engineered with novel human tumor mutations in specified glial cell lineages.
Carnosine negatively modulates pro-oxidant activities of M1 peripheral macrophages and prevents neuroinflammation induced by amyloid-β in microglial cells
Carnosine is a natural dipeptide widely distributed in mammalian tissues and exists at particularly high concentrations in skeletal and cardiac muscles and brain. A growing body of evidence shows that carnosine is involved in many cellular defense mechanisms against oxidative stress, including inhibition of amyloid-β (Aβ) aggregation, modulation of nitric oxide (NO) metabolism, and scavenging both reactive nitrogen and oxygen species. Different types of cells are involved in the innate immune response, with macrophage cells representing those primarily activated, especially under different diseases characterized by oxidative stress and systemic inflammation such as depression and cardiovascular disorders. Microglia, the tissue-resident macrophages of the brain, are emerging as a central player in regulating key pathways in central nervous system inflammation; with specific regard to Alzheimer’s disease (AD) these cells exert a dual role: on one hand promoting the clearance of Aβ via phagocytosis, on the other hand increasing neuroinflammation through the secretion of inflammatory mediators and free radicals. The activity of carnosine was tested in an in vitro model of macrophage activation (M1) (RAW 264.7 cells stimulated with LPS + IFN-γ) and in a well-validated model of Aβ-induced neuroinflammation (BV-2 microglia treated with Aβ oligomers). An ample set of techniques/assays including MTT assay, trypan blue exclusion test, high performance liquid chromatography, high-throughput real-time PCR, western blot, atomic force microscopy, microchip electrophoresis coupled to laser-induced fluorescence, and ELISA aimed to evaluate the antioxidant and anti-inflammatory activities of carnosine was employed. In our experimental model of macrophage activation (M1), therapeutic concentrations of carnosine exerted the following effects: 1) an increased degradation rate of NO into its non-toxic end-products nitrite and nitrate; 2) the amelioration of the macrophage energy state, by restoring nucleoside triphosphates and counterbalancing the changes in ATP/ADP, NAD+/NADH and NADP+/NADPH ratio obtained by LPS + IFN-γ induction; 3) a reduced expression of pro-oxidant enzymes (NADPH oxidase, Cyclooxygenase-2) and of the lipid peroxidation product malondialdehyde; 4) the rescue of antioxidant enzymes expression (Glutathione peroxidase 1, Superoxide dismutase 2, Catalase); 5) an increased synthesis of transforming growth factor-β1 (TGF-β1) combined with the negative modulation of interleukines 1β and 6 (IL-1β and IL-6), and 6) the induction of nuclear factor erythroid-derived 2-like 2 (Nrf2) and heme oxygenase-1 (HO-1). In our experimental model of Aβ-induced neuroinflammation, carnosine: 1) prevented cell death in BV-2 cells challenged with Aβ oligomers; 2) lowered oxidative stress by decreasing the expression of inducible nitric oxide synthase and NADPH oxidase, and the concentrations of nitric oxide and superoxide anion; 3) decreased the secretion of pro-inflammatory cytokines such as IL-1β simultaneously rescuing IL-10 levels and increasing the expression and the release of TGF-β1; 4) prevented Aβ-induced neurodegeneration in primary mixed neuronal cultures challenged with Aβ oligomers and these neuroprotective effects was completely abolished by SB431542, a selective inhibitor of type-1 TGF-β receptor. Overall, our data suggest a novel multimodal mechanism of action of carnosine underlying its protective effects in macrophages and microglia and the therapeutic potential of this dipeptide in counteracting pro-oxidant and pro-inflammatory phenomena observed in different disorders characterized by elevated levels of oxidative stress and inflammation such as depression, cardiovascular disorders, and Alzheimer’s disease.
The cellular phase of Alzheimer’s Disease: from genes to cells
The amyloid cascade hypothesis for Alzheimer disease ((Hardy and Selkoe, 2002; Hardy and Higgins, 1992; Selkoe, 1991), updated in (Karran et al., 2011) provides a linear model for the pathogenesis of AD with Aβ accumulation upstream and Tau pathology, inflammation, synaptic dysfunction, neuronal loss and dementia downstream, all interlinked, initiated and driven by Aβ42 peptides or oligomers. The genetic mutations causing familial Alzheimer disease seem to support this model. The nagging problem remains however that the postulated causal, and especially the ’driving’ role of abnormal Aβ aggregation or Aβ oligomer formation could not be convincingly demonstrated until now. Indeed, many questions (e.g. what causes Aβ toxicity, what is the relation between Aβ and Tau pathology, what causes neuronal death, why is amyloid deposition not correlated with dementia etc…) were already raised when the amyloid hypothesis was conceived 25 years ago. These questions remain in essence unanswered. It seems that the old paradigm is not tenable: the amyloid cascade is too linear, too neurocentric, and does not take into account the long time lag between the biochemical phase i.e. the appearance of amyloid plaques and neuronal tangles and the ultimate clinical phase, i.e. the manifestation of dementia. The pathways linking these two phases must be complex and tortuous. We have called this the cellular phase of AD (De Strooper and Karran, 2016) to suggest that a long period of action and reaction involving neurons, neuronal circuitry but also microglia, astroglia, oligodendrocytes, and the vasculature underlies the disease. In fact it is this long disease process that should be studied in the coming years. While microglia are part of this process, they should not be considered as the only component of the cellular phase. We expect that further clinical investigations and novel tools will allow to diagnose the effects of the cellular changes in the brain and provide clinical signs for this so called preclinical or prodromal AD. Furthermore the better understanding of this phase will lead to completely novel drug targets and treatments and will lead to an era where patients will receive an appropriate therapy according to their clinical stage. In this view anti-amyloid therapy is probably only effective and useful in the very early stage of the disease and AD does no longer equal to dementia. We will discuss in our talk how single cell technology and transplantation of human iPS cells into mouse brain allow to start to map in a systematic way the cellular phase of Alzheimer’s Disease.
Neuro-immune interactions in pain and host defense
The Chiu laboratory focuses on neuro-immune interactions in pain, itch, and tissue inflammation. Dr. Chiu’s research has uncovered molecular interactions between the nervous system, the immune system and microbes that modulates host defense. He has found that sensory neurons can directly detect bacterial pathogens and their toxins to produce pain. Neurons in turn release neuropeptides that modulate immune cells in host defense. These interactions occur at major tissue barriers in the body including the gut, skin and lungs. In this talk, he will discuss these major neuro-immune interactions and how understanding them could lead to novel approaches to treat pain or inflammation.
A2AR-CB2R as a new target to modulate neuroinflammation
FENS Forum 2024
Anti-inflammatory effect of alpha-pinene on the neuroinflammation induced by morphine dependence and withdrawal is mediated by modulating toll-like receptor signaling pathway
FENS Forum 2024
β-Endorphin mitigates UVB-induced epidermal barrier dysfunction through control of inflammation-driven mTORC1 pathways
FENS Forum 2024
Blood biomarkers to monitor neuroinflammation: Insights from hematopoietic stem cell transplantation and gene therapy in X-linked adrenoleukodystrophy
FENS Forum 2024
Breaking the circulus vitiosus of neuroinflammation: Resveratrol attenuates the human glial cell response to cytokines
FENS Forum 2024
Caffeic acid attenuates neuroinflammation and cognitive impairment in streptozotocin-induced diabetic rats: Pivotal role of the cholinergic and purinergic signaling pathways
FENS Forum 2024
Cannabidiol prevention of cognitive deficits in a rat model for Alzheimer’s disease is associated with neuroinflammation
FENS Forum 2024
CD8 T cells play a major role in CNS inflammation and brain atrophy in type I interferon-mediated neuroinflammation of RNaseT2-deficient mice
FENS Forum 2024
Maternal infection during pregnancy induces fetal neuroinflammation, associated with premature oligodendrocyte differentiation and myelin formation, driven by epigenetic changes in oligodendrocyte-specific genes
FENS Forum 2024
Choroid plexus volume as a proxy for neuroinflammation – evaluation of its trans-diagnostic, prognostic, and therapeutic biomarker potential in parkinsonism
FENS Forum 2024
Chronic unpredictable sleep disruption induces changes in locomotor activity, metabolism, and inflammation in Wistar rats
FENS Forum 2024
Combating diet-induced inflammation: Can melanotropin receptors mitigate the effects of excess fat?
FENS Forum 2024
Comparative study of temporal inflammation pattern of two models of spinal cord injury: Contusion versus transection
FENS Forum 2024
Comparing Western diet and LPS as inflammation-related risk factors of sporadic Alzheimer's disease
FENS Forum 2024
Corneal TRPA1 nociceptor: A regulator of neurogenic inflammation in a mouse model of dry eye
FENS Forum 2024
Dietary fatty acid composition drives neuroinflammation and impaired behavior in obesity
FENS Forum 2024
Differential progenitor responses to maternal inflammation in the developing cortex
FENS Forum 2024
Dissecting the impact of prenatal inflammation on astrocytes and Pentraxin 3
FENS Forum 2024
Dual inhibition of ecto-5'-nucleotidase (CD73) and adenosine A2A receptor reduces neuroinflammation and oxidative stress in TNF, IL-1α, C1q-induced neurotoxic astrocytes
FENS Forum 2024
Dysregulated lipid metabolism and neuroinflammation following high-fat diet in the TDP-43Q331K-low transgenic mouse model of ALS-FTD
FENS Forum 2024
The effect of depleting the CNS border-associated macrophages at the pre-symptomatic stage of ALS on neuroinflammation, symptoms, and survival
FENS Forum 2024
Effects of intermittent fasting on neuroinflammation and cognitive impairment in high-fat diet-fed mice
FENS Forum 2024
Electroacupuncture at neurogenic inflammation spots attenuates hepatic damages in bile duct-ligated rats
FENS Forum 2024
Elucidating neuronal activity patterns in autoimmune neuroinflammation: A brain-wide approach
FENS Forum 2024
Evidence of prodromal neuronal hyperexcitability and neuroinflammation in a rodent model of human alpha-synucleinopathy
FENS Forum 2024
Exploring the impact of ibrutinib on microglial inflammation in vitro
FENS Forum 2024
Exploring the neural transcriptomic environment of TLR7-activated neuroinflammation
FENS Forum 2024
Exploring neuroinflammation and neuronal Ca2+ excitability in an Alzheimer's disease mouse model
FENS Forum 2024
Extracellular vesicles from mesenchymal stem cells alter gut microbiota and improve neuroinflammation and motor impairment in rats with mild liver damage
FENS Forum 2024
Extracellular vesicles from poly I:C-infected airway epithelial cells mediate viral signaling in microglia: Implications for neuroinflammation
FENS Forum 2024
Extracellular vesicles from MSCs reverse neuroinflammation in cerebellum and restore motor coordination in hyperammonemic rats
FENS Forum 2024
Golexanolone, a GABAA receptor-modulating steroid antagonist, improves neuroinflammation, fatigue, anxiety, depression, and some cognitive and motor alterations in a rat model of Parkinson's disease
FENS Forum 2024
Human BBB-on-a-chip reveals barrier disruption, endothelial inflammation, and T cell migration under neuroinflammatory conditions
FENS Forum 2024
Human microglia-dependent viral-mediated inflammation impairs retinal organoid development
FENS Forum 2024
Hypoxia as potential regulator of inflammation in Parkinson’s disease
FENS Forum 2024
The impact of clonal hematopoiesis on neuroinflammation after ischemic stroke in a chimeric bone marrow mouse model
FENS Forum 2024
The impact of sauerkraut brine on oxidative stress and inflammation in C57BL/6 mice
FENS Forum 2024
Inflammation's imprint: Unraveling the biomarker landscape of schizophrenia versus acute psychosis
FENS Forum 2024
Influenza-induced maternal inflammation and effect on cortical development
FENS Forum 2024
Investigating the impact of long-term endurance exercise on cognitive function and neuroinflammation in male and female C57BL/6J mice
FENS Forum 2024