Trauma
trauma
Decoding stress vulnerability
Although stress can be considered as an ongoing process that helps an organism to cope with present and future challenges, when it is too intense or uncontrollable, it can lead to adverse consequences for physical and mental health. Social stress specifically, is a highly prevalent traumatic experience, present in multiple contexts, such as war, bullying and interpersonal violence, and it has been linked with increased risk for major depression and anxiety disorders. Nevertheless, not all individuals exposed to strong stressful events develop psychopathology, with the mechanisms of resilience and vulnerability being still under investigation. During this talk, I will identify key gaps in our knowledge about stress vulnerability and I will present our recent data from our contextual fear learning protocol based on social defeat stress in mice.
MRI investigation of orientation-dependent changes in microstructure and function in a mouse model of mild traumatic brain injury
Harnessing Big Data in Neuroscience: From Mapping Brain Connectivity to Predicting Traumatic Brain Injury
Neuroscience is experiencing unprecedented growth in dataset size both within individual brains and across populations. Large-scale, multimodal datasets are transforming our understanding of brain structure and function, creating opportunities to address previously unexplored questions. However, managing this increasing data volume requires new training and technology approaches. Modern data technologies are reshaping neuroscience by enabling researchers to tackle complex questions within a Ph.D. or postdoctoral timeframe. I will discuss cloud-based platforms such as brainlife.io, that provide scalable, reproducible, and accessible computational infrastructure. Modern data technology can democratize neuroscience, accelerate discovery and foster scientific transparency and collaboration. Concrete examples will illustrate how these technologies can be applied to mapping brain connectivity, studying human learning and development, and developing predictive models for traumatic brain injury (TBI). By integrating cloud computing and scalable data-sharing frameworks, neuroscience can become more impactful, inclusive, and data-driven..
Neurosurgery & Consciousness: Bridging Science and Philosophy in the Age of AI
Overview of neurosurgery specialty interplay between neurology, psychiatry and neurosurgery. Discussion on benefits and disadvantages of classifications. Presentation of sub-specialties: trauma, oncology, functional, pediatric, vascular and spine. How does an ordinary day of a neurosurgeon look like; outpatient clinic, emergencies, pre/intra/post operative patient care. An ordinary operation. Myth-busting and practical insights of every day practice. An ordinary operation. Hint for research on clinical problems to be solved. The coming ethical frontiers of neuroprosthetics. In part two we will explore the explanatory gap and its significance. We will review the more than 200 theories of the hard problem of consciousness, from the prevailing to the unconventional. Finally, we are going to reflect on the AI advancements and the claims of LLMs becoming conscious
Pharmacological exploitation of neurotrophins and their receptors to develop novel therapeutic approaches against neurodegenerative diseases and brain trauma
Neurotrophins (NGF, BDNF, NT-3) are endogenous growth factors that exert neuroprotective effects by preventing neuronal death and promoting neurogenesis. They act by binding to their respective high-affinity, pro-survival receptors TrkA, TrkB or TrkC, as well as to p75NTR death receptor. While these molecules have been shown to significantly slow or prevent neurodegeneration, their reduced bioavailability and inability to penetrate the blood-brain-barrier limit their use as potential therapeutics. To bypass these limitations, our research team has developed and patented small-sized, lipophilic compounds which selectively resemble neurotrophins’ effects, presenting preferable pharmacological properties and promoting neuroprotection and repair against neurodegeneration. In addition, the combination of these molecules with 3D cultured human neuronal cells, and their targeted delivery in the brain ventricles through soft robotic systems, could offer novel therapeutic approaches against neurodegenerative diseases and brain trauma.
Traumatic brain injury and the visual sequela
Metabolic-functional coupling of parvalbmunin-positive GABAergic interneurons in the injured and epileptic brain
Parvalbumin-positive GABAergic interneurons (PV-INs) provide inhibitory control of excitatory neuron activity, coordinate circuit function, and regulate behavior and cognition. PV-INs are uniquely susceptible to loss and dysfunction in traumatic brain injury (TBI) and epilepsy but the cause of this susceptibility is unknown. One hypothesis is that PV-INs use specialized metabolic systems to support their high-frequency action potential firing and that metabolic stress disrupts these systems, leading to their dysfunction and loss. Metabolism-based therapies can restore PV-IN function after injury in preclinical TBI models. Based on these findings, we hypothesize that (1) PV-INs are highly metabolically specialized, (2) these specializations are lost after TBI, and (3) restoring PV-IN metabolic specializations can improve PV-IN function as well as TBI-related outcomes. Using novel single-cell approaches, we can now quantify cell-type-specific metabolism in complex tissues to determine whether PV-IN metabolic dysfunction contributes to the pathophysiology of TBI.
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.
The Picower Institute Spring 2023 Symposium "Environmental and Social Determinants of Child Mental Health
Studies show that abuse, neglect or trauma during childhood can lead to lifelong struggles including with mental health. Fortunately research also indicates that solutions and interventions at various stages of life can be developed to help. But even among people who remain resilient or do not experience acute stresses, a lack of opportunity early in life due to poverty or systemic racism can still constrain their ability to realize their full potential. In what ways are health and other outcomes affected by early life difficulty? What can individuals and institutions do to enhance opportunity?" "This daylong event will feature talks by neuroscientists, policy experts, physicians, educators and activists as they discuss how our experiences and biology work together to affect how our minds develop and what can be accomplished in helping people overcome early disadvantages.
Targeting Maladaptive Emotional Memories to Treat Mental Health Disorders: Insights from Rodent Models
Maladaptive emotional memories contribute to the persistence of numerous mental health disorders, including post-traumatic stress disorder (PTSD), drug addiction and obsessive-compulsive disorder (OCD). Using rodent behavioural models of the psychological processes relevant to these disorders, it is possible to identify potential treatment targets for the development of new therapies, including those based upon disrupting the reconsolidation of maladaptive emotional memories. Using examples from rodent models relevant to multiple mental health disorders, this talk will consider some of the opportunities and challenges that this approach provides.
Fragile minds in a scary world: trauma and post traumatic stress in very young children
Post traumatic stress disorder (PTSD) is a prevalent and disabling condition that affects larger numbers of children and adolescents worldwide. Until recently, we have understood little about the nature of PTSD reactions in our youngest children (aged under 8 years old). This talk describes our work over the last 15 years working with this very young age group. It overviews how we need a markedly different PTSD diagnosis for very young children, data on the prevalence of this new diagnostic algorithm, and the development of a psychological intervention and its evaluation in a clinical trial.
Integrating theory-guided and data-driven approaches for measuring consciousness
Clinical assessment of consciousness is a significant issue, with recent research suggesting some brain-damaged patients who are assessed as unconscious are in fact conscious. Misdiagnosis of consciousness can also be detrimental when it comes to general anaesthesia, causing numerous psychological problems, including post-traumatic stress disorder. Avoiding awareness with overdose of anaesthetics, however, can also lead to cognitive impairment. Currently available objective assessment of consciousness is limited in accuracy or requires expensive equipment with major barriers to translation. In this talk, we will outline our recent theory-guided and data-driven approaches to develop new, optimized consciousness measures that will be robustly evaluated on an unprecedented breadth of high-quality neural data, recorded from the fly model system. We will overcome the subjective-choice problem in data-driven and theory-guided approaches with a comprehensive data analytic framework, which has never been applied to consciousness detection, integrating previously disconnected streams of research in consciousness detection to accelerate the translation of objective consciousness measures into clinical settings.
Reconstructing inhibitory circuits in a damaged brain
Inhibitory interneurons govern the sparse activation of principal cells that permits appropriate behaviors, but they among the most vulnerable to brain damage. Our recent work has demonstrated important roles for inhibitory neurons in disorders of brain development, injury and epilepsy. These studies have motivated our ongoing efforts to understand how these cells operate at the synaptic, circuit and behavioral levels and in designing new technologies targeting specific populations of interneurons for therapy. I will discuss our recent efforts examining the role of interneurons in traumatic brain injury and in designing cell transplantation strategies - based on the generation of new inhibitory interneurons - that enable precise manipulation of inhibitory circuits in the injured brain. I will also discuss our ongoing efforts using monosynaptic virus tracing and whole-brain clearing methods to generate brain-wide maps of inhibitory circuits in the rodent brain. By comprehensively mapping the wiring of individual cell types on a global scale, we have uncovered a fundamental strategy to sustain and optimize inhibition following traumatic brain injury that involves spatial reorganization of local and long-range inputs to inhibitory neurons. These recent findings suggest that brain damage, even when focally restricted, likely has a far broader affect on brain-wide neural function than previously appreciated.
Post-traumatic headache
Concussion (mild traumatic brain injury) affects approximately 50 million people annually. Headache is the most common symptom after concussion and persists in up to 50% of those affected for at least one-year. The biological underpinnings of and the efficacy and tolerability of treatments for post-traumatic headache has historically received little attention. While treatment in clinical practice is mostly directly at the underlying phenotype of the headache, persistent post-traumatic headache is considered to be less responsive to treatments used to treat migraine or tension-type headache. Over the past several years, significant pre-clinical research has begun to elucidate the mechanism(s) involved in the development of post-traumatic headache, and a concerted effort to evaluate the efficacy of selected treatments for persistent post-traumatic headache has begun. This presentation will review the epidemiology, pathophysiology, and emerging data on the prevention and treatment of post-traumatic headache.
Epilepsy Genetics – From Family Studies to Polygenic Risk Scores
Whilst epilepsy may be a consequence of an acquired insult including trauma, stroke, and brain tumours, the genetic component to epilepsies has been greatly under-estimated. Considerable progress has recently occurred in the understanding of epilepsy genetics, both at a clinical genetic level and in the basic science of epilepsies. The clinical evidence for genetic components will be first briefly discussed including data from population studies, twin analyses and multiplex family studies. Initial molecular discoveries occurred via classical methods of linkage and gene identification. Recent large-scale hypothesis-free whole exome studies searching for rare variants and genome-wide association studies detecting common variants have been very rewarding. These discoveries have now impacted on clinical practice, especially in severe childhood epilepsies but increasingly so in adult patients. The “genetic background” of patients has long been posited as part of the reason that some patients have epilepsy, or perhaps why some have more severe epilepsy. This has been unmeasurable but now, with the development of polygenic risk scores, the “background” is now in the research foreground. The current and future impact of polygenic risk scores will be explored.
Keeping axons alive after injury: Inhibiting programmed axon death
Activation of pro-degenerative protein SARM1 in response to diverse physical and disease-relevant injuries triggers programmed axon death. Original studies indicated substantially decreased levels of SARM1 were required for neuroprotection. However, we demonstrate that lowering SARM1 levels by 50% in Sarm1 haploinsufficient mice delays axon degeneration in vivo (after sciatic nerve transection), in vitro (in response to diverse traumatic, neurotoxic, and genetic triggers), and partially prevents neurite outgrowth defects in mice lacking pro-survival factor NMNAT2. We also demonstrate the capacity for Sarm1 antisense oligonucleotides to decrease SARM1 levels by more than 50% which delays or prevents programmed axon degeneration in vitro. Combining Sarm1 haploinsufficiency with antisense oligonucleotides further decreases SARM1 levels and prolongs protection after neurotoxic injuries. These data demonstrate that axon protection occurs in a Sarm1 gene-dose responsive manner and that SARM1 lowering agents have therapeutic potential. Thus, antisense oligonucleotide targeting of Sarm1 is a promising therapeutic strategy against diverse triggers of axon degeneration.
Dancing to a Different Tune: TANGO Gives Hope for Dravet Syndrome
The long-term goal of our research is to understand the mechanisms of SUDEP, defined as Sudden, Unexpected, witnessed or unwitnessed, nontraumatic and non-drowning Death in patients with EPilepsy, excluding cases of documented status epilepticus. The majority of SUDEP patients die during sleep. SUDEP is the most devastating consequence of epilepsy, yet little is understood about its causes and no biomarkers exist to identify at risk patients. While SUDEP accounts for 7.5-20% of all epilepsy deaths, SUDEP risk in the genetic epilepsies varies with affected genes. Patients with ion channel gene variants have the highest SUDEP risk. Indirect evidence variably links SUDEP to seizure-induced apnea, pulmonary edema, dysregulation of cerebral circulation, autonomic dysfunction, and cardiac arrhythmias. Arrhythmias may be primary or secondary to hormonal or metabolic changes, or autonomic discharges. When SUDEP is compared to Sudden Cardiac Death secondary to Long QT Syndrome, especially to LQT3 linked to variants in the voltage-gated sodium channel (VGSC) gene SCN5A, there are parallels in the circumstances of death. To gain insight into SUDEP mechanisms, our approach has focused on channelopathies with high SUDEP incidence. One such disorder is Dravet syndrome (DS), a devastating form of developmental and epileptic encephalopathy (DEE) characterized by multiple pharmacoresistant seizure types, intellectual disability, ataxia, and increased mortality. While all patients with epilepsy are at risk for SUDEP, DS patients may have the highest risk, up to 20%, with a mean age at SUDEP of 4.6 years. Over 80% of DS is caused by de novo heterozygous loss-of-function (LOF) variants in SCN1A, encoding the VGSC Nav1.1 subunit, resulting in haploinsufficiency. A smaller cohort of patients with DS or a more severe DEE have inherited, homozygous LOF variants in SCN1B, encoding the VGSC 1/1B non-pore-forming subunits. A related DEE, Early Infantile EE (EIEE) type 13, is linked to de novo heterozygous gain-of-function variants in SCN8A, encoding the VGSC Nav1.6. VGSCs underlie the rising phase and propagation of action potentials in neurons and cardiac myocytes. SCN1A, SCN8A, and SCN1B are expressed in both the heart and brain of humans and mice. Because of this, we proposed that cardiac arrhythmias contribute to the mechanism of SUDEP in DEE. We have taken a novel approach to the development of therapeutics for DS in collaboration with Stoke Therapeutics. We employed Targeted Augmentation of Nuclear Gene Output (TANGO) technology, which modulates naturally occurring, non-productive splicing events to increase target gene and protein expression and ameliorate disease phenotype in a mouse model. We identified antisense oligonucleotides (ASOs) that specifically increase the expression of productive Scn1a transcript in human and mouse cell lines, as well as in mouse brain. We showed that a single intracerebroventricular dose of a lead ASO at postnatal day 2 or 14 reduced the incidence of electrographic seizures and SUDEP in the F1:129S-Scn1a+/- x C57BL/6J mouse model of DS. Increased expression of productive Scn1a transcript and NaV1.1 protein were confirmed in brains of treated mice. Our results suggest that TANGO may provide a unique, gene-specific approach for the treatment of DS.
Converging mechanisms of epileptogenesis after brain injury
Traumatic brain injury (TBI), a leading cause of acquired epilepsy, results in primary cellular injury as well as secondary neurophysiological and inflammatory responses which contribute to epileptogenesis. I will present our recent studies identifying a role for neuro-immune interactions, specifically, the innate immune receptor Toll-like receptor 4 (TLR4), in enhancing network excitability and cell loss in hippocampal dentate gyrus early after concussive brain injury. I will describe results indicating that the transient post-traumatic increases in dentate neurogenesis which occurs during the same early post-injury period augments dentate network excitability and epileptogenesis. I will provide evidence for the beneficial effects of targeting TLR4 and neurogenesis early after brain injury in limiting epileptogenesis. We will discuss potential mechanisms for convergence of the post-traumatic neuro-immune and neurogenic changes and the implications for therapies to reduce neurological deficits and epilepsy after brain injury.
Microbiome and behaviour: Exploring underlying mechanisms
Environmental insults alter brain function and behaviour inboth rodents and people. One putative underlying mechanism that has receivedsubstantial attention recently is the gut microbiota, the ecosystem ofsymbiotic microorganisms that populate the intestinal tract, which is known toplay a role in brain health and function via the gut-brain axis. Two keyenvironmental insults known to affect both brain function and behaviour, andthe gut microbiome, are poor diet and psychological stress. While there isstrong evidence for interactions between the microbiome and host physiology inthe context of chronic stress, little is known about the role of the microbiomein the host response to acute stress. Determining the underlying mechanisms bywhich stress may provoke functional changes in the gut and brain is criticalfor developing therapeutics to alleviate adverse consequences of traumaticstress.
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.
The Picower Institute Spring 2021 Symposium: Early Life Stress & Mental Health
Though studies show that abuse, neglect or trauma during childhood can lead to lifelong lifelong struggles including in mental health, research also indicates that solutions and interventions at various stages of life can be developed to help. And while many people manage to remain resilient, a lack of opportunity early in life, including because of poverty and systemic racism, can constrain their ability to realize their full potential. In what ways are health and other outcomes affected? How can systems instead restore opportunity? "The Picower Institute for Learning and Memory's biennial spring symposium, 'Early Life Stress & Mental Health,' will examine these issues. The daylong event will feature talks by neuroscientists, policy experts, physicians, educators and activists as they discuss how our experiences and biology work together to affect how our minds develop and what can be accomplished in helping people overcome early disadvantages.
Psychedelics and the Pharmacology of Consciousness
The study of altered states of consciousness has long had the potential to provide important insight into the nature of consciousness. In recent years there has been a resurgence of research and public interest in atypical or altered states of consciousness. These have focused both on conditions in which consciousness is considered to be impaired due to brain trauma or enhanced in some way through mediation practices or ingestion of psychedelics. The talk will begin with a brief overview of recent scientific approaches to understanding these different types of altered consciousness. The remainder of the talk will focus on lab-based experiments conducted by myself and others looking at the effects of serotoninergic hallucinogens (i.e. psilocybin and LSD) on perceptual and cognitive function. Together this body of research provides important new insights for the scientific study of consciousness and an initial understanding of the neuropharmacological mechanisms underlying conscious experience.
The Impact of Racism-related Stress on Neurobiological Systems in Black Americans”
Black Americans experience diverse racism-related stressors throughout the lifespan. Disproportionately high trauma exposure, economic disadvantage, explicit racism and inequitable treatment are stressors faced by many Black Americans. These experiences have a cumulative negative impact on psychological and physical health. However, little is understood about how experiences of racism, such as discrimination, can mediate health outcomes via their effects on neurobiology. I will present clinical, behavioral, physiological and neurobiological data from Black American participants in the Grady Trauma Project, a longstanding study of trauma conducted in inner-city Atlanta. These data will be discussed in the context of both risk and resilience/adaptation perspectives. Finally, recommendations for future clinical neuroscience research and targets for intervention in marginalized populations will be discussed.
Brain Awareness Week @ IITGN
Traumatic injury in the nervous system leads to devastating consequences such as paralysis. The regenerative capacity of the nervous system is limited in adulthood. In this talk, Dr. Anindya would be sharing how the simple nematode C. elegans with its known connectome can inform us about the biology of nervous system repair.
The many faces of KCC2 in the generation and suppression of seizures
KCC2, best known as the neuron-specific chloride extruder that sets the strength and polarity of GABAergic Cl-currents, is a multifunctional molecule which interacts with other ion-regulatory proteins and (structurally) with the neuronal cytoskeleton. Its multiple roles in the generation and suppression of seizures have been widely studied. In my talk, I will address some fundamental issues which are relevant in this field of research: What are EGABA shifts about? What is the role of KCC2 in shunting inhibition? What is meant by “the balance between excitation and inhibition” and, in this context, by the “NKCC1/KCC2 ratio”? Is down-regulation of KCC2 following neuronal trauma a manifestation of adaptive or maladaptive ionic plasticity? Under what conditions is K-Cl cotransport by KCC2 promoting seizures? Should we pay more attention to KCC2 as molecule involved in dendritic spine formation in brain areas such as the hippocampus? Most of these points are of potential importance also in the design of KCC2-targeting drugs and genetic manipulations aimed at combating seizures.
Programmed Axon Death and its Roles in Human Disease
Axons degenerate before the neuronal soma in many neurodegenerative diseases. Programmed axon death (Wallerian degeneration) is a widely-occurring mechanism of axon loss that is well understood and preventable in animals. Its aberrant activation by mutation of the pro-survival gene Nmnat2 directly causes axonopathy in mice with severity ranging from mild polyneuropathy to perinatal lethality. Rare biallelic mutations in the homologous human gene cause related phenotypes in patients. NMNAT2 is a negative regulator of the prodegenerative NADase SARM1. Constitutive activation of SARM1 is cytotoxic and the human SARM1 locus is significantly associated with sporadic ALS. Another negative regulator, STMN2, has also been implicated in ALS, where it is commonly depleted downstream of TDP-43. In mice, programmed axon death can be robustly blocked by deletion of Sarm1, or by overexpression, axonal targeting and/or stabilization of various NMNAT isoforms. This alleviates models of many human disorders including some forms of peripheral neuropathy, motor neuron diseases, glaucoma, Parkinson’s disease and traumatic brain injury, and it confers lifelong rescue on the lethal Nmnat2 null phenotype and other conditions. Drug discovery programs now aim to achieve similar outcomes in human disease. In order to optimize the use of such drugs, we have characterized a range of human NMNAT2 and SARM1 functional variants that underlie a spectrum of axon vulnerability in the human population. Individuals at the vulnerable end of this spectrum are those most likely to benefit from drugs blocking programmed axon death, and disorders associated with these genotypes are promising indications in which to apply them.
Affordable Robots/Computer Systems to Identify, Assess, and Treat Impairment After Brain Injury
Non-traumatic brain injury due to stroke, cerebral palsy and HIV often result in serious long-term disability worldwide, affecting more than 150 million persons globally; with the majority of persons living in low and middle income countries. These diseases often result in varying levels of motor and cognitive impairment due to brain injury which then affects the person’s ability to complete activities of daily living and fully participate in society. Increasingly advanced technologies are being used to support identification, diagnosis, assessment, and therapy for patients with brain injury. Specifically, robot and mechatronic systems can provide patients, physicians and rehabilitation clinical providers with additional support to care for and improve the quality of life of children and adults with motor and cognitive impairment. This talk will provide a brief introduction to the area of rehabilitation robotics and, via case studies, illustrate how computer/technology-assisted rehabilitation systems can be developed and used to assess motor and cognitive impairment, detect early evidence of functional impairment, and augment therapy in high and low-resource settings.
How sleep remodels the brain
50 years ago it was found that sleep somehow made memories better and more permanent, but neither sleep nor memory researchers knew enough about sleep and memory to devise robust, effective tests. Today the fields of sleep and memory have grown and what is now understood is astounding. Still, great mysteries remain. What is the functional difference between the subtly different slow oscillation vs the slow wave of sleep and do they really have opposite memory consolidation effects? How do short spindles (e.g. <0.5 s as in schizophrenia) differ in function from longer ones and are longer spindles key to integrating new memories with old? Is the nesting of slow oscillations together with sleep spindles and hippocampal ripples necessary? What happens if all else is fine but the neurochemical environment is altered? Does sleep become maladaptive and “cement” memories into the hippocampal warehouse where they are assembled, together with all of their emotional baggage? Does maladaptive sleep underlie post-traumatic stress disorder and other stress-related disorders? How do we optimize sleep characteristics for top emotional and cognitive function? State of the art findings and current hypotheses will be presented.
Electrophysiology application for optic nerve and the central nervous system diseases
Electrophysiology of eye and visual pathway is useful tool in ophthalmology and neurology. It covers a few examinations to find out if defect of vision is peripheral or central. Visual evoked potentials (VEP) are most frequently used in neurology and neuroophthalmology. VEP are evoked by flash or pattern stimulations. The combination of these both examinations gives more information about the visual pathway. It is very important to remember that VEP originate in the retina and reflect its function as well. In many cases not only VEP but also electroretinography (ERG) is essential for diagnosis. The seminar presents basic electrophysiological procedures used for diagnosis and follow-up of optic neuropathies and some of central nervous system diseases which affect vision (mostly multiple sclerosis, CNS tumors, stroke, traumas, intracranial hypertension).
Association of insulin-like growth factor 1 with post-traumatic brain injury sleep disorders: A longitudinal study
FENS Forum 2024
Centrally located transient receptor potential ankyrin 1 ion channel may exert diverse impact on the symptoms of posttraumatic stress disorder in mice
FENS Forum 2024
Childhood trauma in the adult brain: The relationship between adverse childhood experiences, brain structure, and mental health in late adulthood
FENS Forum 2024
Correlation between neuroprotection in a tauopathy environment following trauma and delayed astrogliosis in a cohort study
FENS Forum 2024
Critical fear: Developmental trajectories of traumatic life experiences during specific sensitive periods
FENS Forum 2024
Delivery of PTEN inhibitory peptide PAP2 to promote regeneration in a mouse model of traumatic brain injury
FENS Forum 2024
Effects of dietary supplementation with deuterated polyunsaturated fatty acids in experimental traumatic brain injury
FENS Forum 2024
Enhancing recovery after traumatic brain injury by pharmacological modulation of the PTEN/AKT pathway
FENS Forum 2024
The epicenter of trauma resilience?
FENS Forum 2024
Functional implications of traumatic brain injury-induced changes in serine/threonine kinase activity and peptide phosphorylation in mouse cortex
FENS Forum 2024
Functional interaction between traumatic brain injury and Alzheimer’s disease in next-gen humanized mice models
FENS Forum 2024
Functional and morphological alterations of parvalbumin-positive interneurons in the somatosensory cortex of mice in the early phase after traumatic brain injury
FENS Forum 2024
Hyperbaric oxygenation enhances neurogenesis in subventricular zone after traumatic brain injury
FENS Forum 2024
Intervention with a medical multi-nutrient in traumatic brain injury – a feasibility trial
FENS Forum 2024
Investigating the glucose transporter 2 positive cells in the medial prefrontal cortex and their association with posttraumatic stress disorder in a mice model
FENS Forum 2024
Mitochondrial dysfunction underlies impaired neurovascular coupling following traumatic brain injury
FENS Forum 2024
Nestin-Cre-mediated progranulin expression partially rescues exacerbated consequences in progranulin-deficient mice after traumatic brain injury
FENS Forum 2024
Oxytocin as a novel therapeutic target to reduce neuroinflammation and protect brain development following pediatric traumatic brain injury
FENS Forum 2024
Persistent astrogliosis and microgliosis in the perilesional cortex after traumatic brain injury in male and female rats
FENS Forum 2024
Pharmacological evaluation of novel non-nucleotide purine derivatives as P2X7 antagonists for the treatment of neuroinflammation in traumatic brain injury
FENS Forum 2024
Sex-dependent effects of voluntary physical exercise on object recognition memory restoration after traumatic brain injury in middle-aged rats
FENS Forum 2024
Structural Brain Changes after Potentially Traumatic Events
FENS Forum 2024
Temporal analysis of the infiltration dynamics of pro-inflammatory cytokine-producing innate and adaptive immune cells following experimental traumatic brain injury in mice
FENS Forum 2024
Temporal evolution of traumatic memory engrams in a mouse model of early-life stress
FENS Forum 2024
Treatment of traumatic brain injury by atorvastatin-loaded PEGylated liposome
FENS Forum 2024
Unmasking microglial responses to traumatic brain injury and neural probes through morphometric analysis – MicroFACE
FENS Forum 2024
Unveiling microvascular occlusions in traumatic brain injury: Insights into blood-brain barrier permeability using super-bright nanoparticles
FENS Forum 2024
VSX1 expression in V2 precursor cells at embryological stages could be used to follow spared V2 interneurons after a traumatic injury in adulthood
FENS Forum 2024
Distant mild traumatic brain injury: a review of electrophysiological and imaging findings at late times after concussion
Neuromatch 5