Noninvasive detection of mild traumatic brain injury (mTBI) is important for evaluating acute through chronic effects head injuries, particularly after repetitive impacts. To better detect abnormalities from mTBI, we performed longitudinal studies (baseline, 3, 6, and 42 days) using magnetic resonance diffusion tensor imaging (DTI) kurtosis (DKI) in adult mice mTBI (r-mTBI; daily × 5) or sham procedure. This r-mTBI produced righting reflex delay was first characterized the corpus callosum to...

Traumatic brain injury (TBI) patients often exhibit slowed information processing speed that can underlie diverse symptoms. Processing depends on neural circuit function at synapses, in the soma, and along axons. Long axons white matter (WM) tracts are particularly vulnerable to TBI. We hypothesized disrupted axon–myelin interactions slow or block action potential conduction WM may contribute after Concussive TBI male/female mice was used produce traumatic axonal corpus callosum (CC),...

The downstream targets of amyloid β (Aβ)‐oligomers remain elusive. One hypothesis is that Aβ‐oligomers interrupt axonal transport. Although previous studies have demonstrated Aβ‐induced transport blockade, early effects low‐n soluble on unclear. Furthermore, the cargo selectivity for such deficits (if any) or specific Aβ motility kinetics transported cargoes are also unknown. Toward this, we visualized vesicles in cultured hippocampal neurons treated with picomolar ( p m ) levels...

Abstract Traumatic brain injury (TBI) causes chronic symptoms and increased risk of neurodegeneration. Axons in white matter tracts, such as the corpus callosum (CC), are critical components neural circuits particularly vulnerable to TBI. Treatments needed protect axons from traumatic mitigate post-traumatic SARM1 protein is a central driver axon degeneration through conserved molecular pathway. Sarm1 −/− mice with knockout (KO) gene enable genetic proof-of-concept testing pathway...

Non-invasive imaging has the potential to play a crucial role in characterization and translation of experimental animal models investigate human brain development disorders, especially when employed study that more accurately represent features neuroanatomy. The purpose this was build make available MRI DTI templates analysis tools for ferret as is well-suited species pre-clinical studies with folded cortical surface, relatively high white matter volume body dimensions allow scanners. Four...

During the acute time period following traumatic brain injury (TBI), noninvasive imaging tools such as magnetic resonance (MRI) can provide important information about clinical and pathological features of may help predict long-term outcomes. In addition to standard approaches, several quantitative MRI techniques including relaxometry diffusion have been identified promising reporters cellular alterations after TBI greater sensitivity specificity for identifying abnormalities especially in...

Experimental brain trauma activates quiescent neural stem cells (NSCs) to increase neuronal progenitor cell proliferation in the adult rodent brain. Previous studies have shown focal contusion form of a unilateral controlled cortical impact (CCI) stimulates NSCs bilaterally neurogenesis hippocampus.In this study we clarified bi-lateral effects CCI on subventricular zone (SVZ) NSC niche and olfactory bulb mice. By varying depth from 1 mm 2 depth, show left somatosensory cortex resulted graded...

The role of epigenetic regulators in the control adult neurogenesis is largely undefined. We show that histone demethylase enzyme Kdm5b (Jarid1b) negatively regulates from subventricular zone (SVZ) neural stem cells (NSCs) culture. shRNA-mediated depletion proliferating NSCs decreased proliferation rates and reduced neurosphere formation When transferred to differentiation culture conditions, Kdm5b-depleted migrated neurospheres with increased velocity. Whole-genome expression screening...

Damage to long axons in white matter tracts is a major pathology closed head traumatic brain injury (TBI). Acute TBI treatments are needed that protect against axon damage and promote recovery of function prevent term symptoms neurodegeneration. Our prior characterization demyelination after led us examine repurposing 4-aminopyridine (4-AP), an FDA-approved inhibitor voltage-gated potassium (Kv) channels. 4-AP currently indicated provide symptomatic relief for patients with chronic stage...

Abstract White matter damage is an important consequence of traumatic brain injury (TBI) in humans. Unlike rodents, ferrets have a substantial amount white and gyrencephalic brain; therefore, they may represent ideal small mammal model to study human‐pertinent consequences TBI. Here we report immunohistochemical behavioral results after controlled cortical impact (CCI) the sensorimotor cortex adult male ferrets. We assessed inflammation neocortex matter, behavior at 1 day post 1, 4, 16 weeks...

Mild traumatic brain injury (mTBI) is highly prevalent but lacks both research tools with adequate sensitivity to detect cellular alterations that accompany mild and pre-clinical models are able robustly mimic hallmark features of human TBI. To address these related challenges, high-resolution diffusion tensor MRI (DTI) analysis was performed in a model TBI the ferret – species that, unlike rodents, share humans gyrencephalic cortex high white matter volume. A set DTI image were optimized...

Abstract Traumatic brain injury (TBI) is often more complicated than a single head injury. An extreme example of this point may be military service members who experience spectrum exposures over prolonged period under stressful conditions. Understanding the effects complex can inform evaluation and care to prevent persistent symptoms. We designed longitudinal series non‐invasive procedures in adult mice evaluate mild stress exposures. assessed anxiety, depression, sleep–wake dysfunction as...

ABSTRACT Leukemia/lymphoma‐related factor (LRF), a zinc‐finger transcription encoded by Zbtb7a , is protooncogene that regulates differentiation in diverse cell lineages, and the CNS, its function relatively unexplored. This study first to examine role of LRF CNS pathology. We examined expression murine viral model spinal cord demyelination with clinically relevant lesion characteristics. was rarely expressed oligodendrocyte progenitors (OP) yet, detected nuclei majority oligodendrocytes...

The potential effects of blast exposure on the brain health military personnel have raised concerns and led to increased surveillance exposures. Neuroimaging studies reported white matter abnormalities in brains service members with a history exposure. However, microstructure remain poorly understood. As novel approach screen for effects, transgenic mice that express fluorescent reporters sensitively detect axon damage myelin remodeling were exposed simulated repetitive blasts (once/day 5...

ABSTRACT Traumatic brain injury (TBI) is often more complicated than a single head injury. An extreme example of this point may be military service members who experience spectrum exposures over prolonged period under stressful conditions. Understanding the effects complex can support proper evaluation and care for patients experiencing persistent symptoms. We designed longitudinal series non-invasive procedures in adult mice to evaluate mild exposures. assessed anxiety, depression,...

ABSTRACT Damage to long axons in white matter tracts is a major pathology closed head traumatic brain injury (TBI). Acute TBI treatments are needed that protect against axon damage and promote recovery of function prevent term symptoms neurodegeneration. Our prior characterization demyelination after led us examine repurposing 4-aminopyridine (4-AP), an FDA-approved inhibitor voltage-gated potassium (Kv) channels. 4-AP currently indicated provide symptomatic relief for patients with chronic...

ABSTRACT Traumatic brain injury (TBI) causes chronic symptoms and increased risk of neurodegeneration. Axons in white matter tracts, such as the corpus callosum (CC), are critical components neural circuits particularly vulnerable to TBI. Treatments needed protect axons from traumatic mitigate post-traumatic The Sarm1 gene is a central driver axon degeneration through conserved molecular pathway. -/- mice with knockout (KO) enable genetic proof-of-concept testing inactivation therapeutic...