traumatic brain injury

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..

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.

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.

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.

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

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.

Fate mapping of peripherally derived macrophages after traumatic brain injury

Application of the ceftriaxone changes the GLT-1 distribution after traumatic brain injury

Effects of dietary supplementation with deuterated polyunsaturated fatty acids in experimental traumatic brain injury

FENS Forum 2024

Delivery of PTEN inhibitory peptide PAP2 to promote regeneration in a mouse model of traumatic brain injury

FENS Forum 2024

This is an injured brain on drugs: Examining the effects of modafinil administration on repetitive mild traumatic brain injury outcomes in adult rats

Altered expression of peripheral microRNAs and pathway signaling after mild traumatic brain injury

Cellular Senescence and Neuroinflammation Following Controlled Cortical Impact Traumatic Brain Injury in Juvenile Mice

Challenging the role of oligodendrocytes upon traumatic brain injury

Chronic intracerebroventricular administration of orexin-A does not modify behavioural outcomes following repetitive mild traumatic brain injury in rats

BMX deficiency alleviates cognitive and motor impairment after traumatic brain injury

Drebrin controls scar formation and astrocyte reactivity upon traumatic brain injury by regulating membrane trafficking

Effects of pioglitazone on the cortical damage and motor performance following traumatic brain injury in the rat

Emulating the Secondary Injuries of Traumatic Brain Injury and the Exploration of Neurotherapeutics

Evaluation of repetitive mild traumatic brain injury by fluorescence and FDG PET imaging

A Gut-Brain Connection: Gut Microbiome Composition is Differentially Altered After Repetitive Mild Traumatic Brain Injury in Adolescent and Adult Rats

Human Platelet Proteome improves traumatic brain injury in animal models

The impact of a pre-existing Toxoplasma gondii infection following traumatic brain injury in mice

Ketogenic diet protects the brain against weight decrease after traumatic brain injury

Longitudinal Volume Loss after Traumatic Brain Injury Predicts Vestibular Dysfunction

Neuroprotective effect of physical exercise after traumatic brain injury: influence of the onset delay and pre-injury fitness

A novel rat model of heterotopic ossification after polytrauma with traumatic brain injury

Optimized protocol reveals modulation of anesthetic preconditioning by genetic background in a Drosophila melanogaster (fruit fly) model of polytrauma with traumatic brain injury (TBI)

Role of mitochondrial fission-fusion dynamics in progressive neurodegeneration and memory deficit after traumatic brain injury

Serum Neurofilament Light As A Biomarker Of Vulnerability To Repeated Mild Traumatic Brain Injury In Adolescent Male Rats

SST-positive GABAergic interneurons counterbalance cortical hyperexcitability after traumatic brain injury in mice by a switch of α-subunits in L-type voltage-gated calcium channels

Temporal dynamics of neuroinflammation following controlled cortical impact traumatic brain injury in juvenile and adult mice

Traumatic brain injury and its effects on the reaction of glial cells

Association of insulin-like growth factor 1 with post-traumatic brain injury sleep disorders: A longitudinal study

FENS Forum 2024

Enhancing recovery after traumatic brain injury by pharmacological modulation of the PTEN/AKT pathway

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Functional implications of traumatic brain injury-induced changes in serine/threonine kinase activity and peptide phosphorylation in mouse cortex

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Functional interaction between traumatic brain injury and Alzheimer’s disease in next-gen humanized mice models

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Functional and morphological alterations of parvalbumin-positive interneurons in the somatosensory cortex of mice in the early phase after traumatic brain injury

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Hyperbaric oxygenation enhances neurogenesis in subventricular zone after traumatic brain injury

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Intervention with a medical multi-nutrient in traumatic brain injury – a feasibility trial

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Mitochondrial dysfunction underlies impaired neurovascular coupling following traumatic brain injury

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Nestin-Cre-mediated progranulin expression partially rescues exacerbated consequences in progranulin-deficient mice after traumatic brain injury

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Oxytocin as a novel therapeutic target to reduce neuroinflammation and protect brain development following pediatric traumatic brain injury

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Pharmacological evaluation of novel non-nucleotide purine derivatives as P2X7 antagonists for the treatment of neuroinflammation in 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

Sex-dependent effects of voluntary physical exercise on object recognition memory restoration after traumatic brain injury in middle-aged rats

FENS Forum 2024