Myelin loss and oligodendrocyte pathology in white matter tracts following traumatic brain injury in the rat

2013 ◽  
Vol 38 (1) ◽  
pp. 2153-2165 ◽  
Author(s):  
J. Flygt ◽  
A. Djupsjö ◽  
F. Lenne ◽  
N. Marklund
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
White Matter Tracts

scholarly journals The Subventricular Zone in the Immature Piglet Brain: Anatomy and Exodus of Neuroblasts into White Matter after Traumatic Brain Injury

2015 ◽  
Vol 37 (2) ◽  
pp. 115-130 ◽  
Author(s):  
Beth A. Costine ◽  
Symeon Missios ◽  
Sabrina R. Taylor ◽  
Declan McGuone ◽  
Colin M. Smith ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Subventricular Zone ◽  
Mesh Network ◽  
Human Infant ◽  
Ependymal Cells ◽  
Postnatal Neurogenesis ◽  
White Matter Tracts ◽  
Stimulation Of

Stimulation of postnatal neurogenesis in the subventricular zone (SVZ) and robust migration of neuroblasts to the lesion site in response to traumatic brain injury (TBI) is well established in rodent species; however, it is not yet known whether postnatal neurogenesis plays a role in repair after TBI in gyrencephalic species. Here we describe the anatomy of the SVZ in the piglet for the first time and initiate an investigation into the effect of TBI on the SVZ architecture and the number of neuroblasts in the white matter. Among all ages of immaturity examined the SVZ contained a dense mesh network of neurogenic precursor cells (doublecortin+) positioned directly adjacent to the ependymal cells (ventricular SVZ, Vsvz) and neuroblasts organized into chains that were distinct from the Vsvz (abventricular SVZ, Asvz). Though the architecture of the SVZ was similar among ages, the areas of Vsvz and Asvz neuroblast chains declined with age. At postnatal day (PND) 14 the white matter tracts have a tremendous number of individual neuroblasts. In our scaled cortical impact model, lesion size increased with age. Similarly, the response of the SVZ to injury was also age dependent. The younger age groups that sustained the proportionately smallest lesions had the largest SVZ areas, which further increased in response to injury. In piglets that were injured at 4 months of age and had the largest lesions, the SVZ did not increase in response to injury. Similar to humans, swine have abundant gyri and gyral white matter, providing a unique platform to study neuroblasts potentially migrating from the SVZ to the lesioned cortex along these white matter tracts. In piglets injured at PND 7, TBI did not increase the total number of neuroblasts in the white matter compared to uninjured piglets, but redistribution occurred with a greater number of neuroblasts in the white matter of the hemisphere ipsilateral to the injury compared to the contralateral hemisphere. At 7 days after injury, less than 1% of neuroblasts in the white matter were born in the 2 days following injury. These data show that the SVZ in the piglet shares many anatomical similarities with the SVZ in the human infant, and that TBI had only modest effects on the SVZ and the number of neuroblasts in the white matter. Piglets at an equivalent developmental stage to human infants were equipped with the largest SVZ and a tremendous number of neuroblasts in the white matter, which may be sufficient in lesion repair without the dramatic stimulation of neurogenic machinery. It has yet to be determined whether neurogenesis and migrating neuroblasts play a role in repair after TBI and/or whether an alteration of normal migration during active postnatal population of brain regions is beneficial in species with gyrencephalic brains.

scholarly journals Diffuse disconnectivity in traumatic brain injury: a resting state fMRI and DTI study

2012 ◽  
Vol 3 (1) ◽  
Author(s):  
Cheuk Tang ◽  
Emily Eaves ◽  
Kristen Dams-O’Connor ◽  
Lap Ho ◽  
Eric Leung ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Default Mode Network ◽  
Resting State ◽  
Axonal Injury ◽  
White Matter Integrity ◽  
White Matter Tracts ◽  
Imaging Protocol ◽  
Default Mode

AbstractDiffuse axonal injury is a common pathological consequence of Traumatic Brain Injury (TBI). Diffusion Tensor Imaging is an ideal technique to study white matter integrity using the Fractional Anisotropy (FA) index which is a measure of axonal integrity and coherence. There have been several reports showing reduced FA in individuals with TBI, which suggest demyelination or reduced fiber density in white matter tracts secondary to injury. Individuals with TBI are usually diagnosed with cognitive deficits such as reduced attention span, memory and executive function. In this study we sought to investigate correlations between brain functional networks, white matter integrity, and TBI severity in individuals with TBI ranging from mild to severe. A resting state functional magnetic resonance imaging protocol was used to study the default mode network in subjects at rest. FA values were decreased throughout all white matter tracts in the mild to severe TBI subjects. FA values were also negatively correlated with TBI injury severity ratings. The default mode network showed several brain regions in which connectivity measures were higher among individuals with TBI relative to control subjects. These findings suggest that, subsequent to TBI, the brain may undergo adaptation responses at the cellular level to compensate for functional impairment due to axonal injury.

Facial affect recognition linked to damage in specific white matter tracts in traumatic brain injury

2014 ◽  
Vol 10 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Helen M. Genova ◽  
Venkateswaran Rajagopalan ◽  
Nancy Chiaravalloti ◽  
Allison Binder ◽  
John Deluca ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Facial Affect ◽  
Affect Recognition ◽  
Facial Affect Recognition ◽  
White Matter Tracts

scholarly journals A robust method for investigating thalamic white matter tracts after traumatic brain injury

NeuroImage ◽  
2012 ◽  
Vol 63 (2) ◽  
pp. 779-788 ◽  
Author(s):  
Letizia Squarcina ◽  
Alessandra Bertoldo ◽  
Timothy E. Ham ◽  
Rolf Heckemann ◽  
David J. Sharp
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Robust Method ◽  
White Matter Tracts

Volumetric Asymmetries of White Matter Tracts in Traumatic Brain Injury

2018 ◽  
Vol 99 (11) ◽  
pp. e183
Author(s):  
Andrei Vakhtin ◽  
Ansgar Furst ◽  
Dana Waltzman ◽  
J. Ashford ◽  
Max Wintermark ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
White Matter Tracts

scholarly journals Genetic inactivation of SARM1 axon degeneration pathway improves outcome trajectory after experimental traumatic brain injury based on pathological, radiological, and functional measures

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Donald V. Bradshaw ◽  
Andrew K. Knutsen ◽  
Alexandru Korotcov ◽  
Genevieve M. Sullivan ◽  
Kryslaine L. Radomski ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Diffusion Tensor ◽  
Traumatic Injury ◽  
Axon Degeneration ◽  
White Matter Tracts ◽  
Sleep Behavior ◽  
Increased Risk ◽  
Post Traumatic

AbstractTraumatic 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 of neural circuits and particularly vulnerable to TBI. Treatments are needed to protect axons from traumatic injury and mitigate post-traumatic neurodegeneration. SARM1 protein is a central driver of axon degeneration through a conserved molecular pathway. Sarm1−/− mice with knockout (KO) of the Sarm1 gene enable genetic proof-of-concept testing of the SARM1 pathway as a therapeutic target. We evaluated Sarm1 deletion effects after TBI using a concussive model that causes traumatic axonal injury and progresses to CC atrophy at 10 weeks, indicating post-traumatic neurodegeneration. Sarm1 wild-type (WT) mice developed significant CC atrophy that was reduced in Sarm1 KO mice. Ultrastructural classification of pathology of individual axons, using electron microscopy, demonstrated that Sarm1 KO preserved more intact axons and reduced damaged or demyelinated axons. Longitudinal MRI studies in live mice identified significantly reduced CC volume after TBI in Sarm1 WT mice that was attenuated in Sarm1 KO mice. MR diffusion tensor imaging detected reduced fractional anisotropy in both genotypes while axial diffusivity remained higher in Sarm1 KO mice. Immunohistochemistry revealed significant attenuation of CC atrophy, myelin loss, and neuroinflammation in Sarm1 KO mice after TBI. Functionally, Sarm1 KO mice exhibited beneficial effects in motor learning and sleep behavior. Based on these findings, Sarm1 inactivation can protect axons and white matter tracts to improve translational outcomes associated with CC atrophy and post-traumatic neurodegeneration.

scholarly journals Genetic inactivation of SARM1 axon degeneration pathway improves outcome trajectory after experimental traumatic brain injury based on pathological, radiological, and functional measures

2021 ◽  
Author(s):  
Donald V. Bradshaw ◽  
Andrew K. Knutsen ◽  
Alexandru Korotcov ◽  
Genevieve M. Sullivan ◽  
Kryslaine L. Radomski ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Diffusion Tensor ◽  
Traumatic Injury ◽  
Axon Degeneration ◽  
White Matter Tracts ◽  
Increased Risk ◽  
Post Traumatic ◽  
Critical Components

ABSTRACTTraumatic 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 of neural circuits and particularly vulnerable to TBI. Treatments are needed to protect axons from traumatic injury and mitigate post-traumatic neurodegeneration. The Sarm1 gene is a central driver of axon degeneration through a conserved molecular pathway. Sarm1-/- mice with knockout (KO) of the Sarm1 gene enable genetic proof-of-concept testing of Sarm1 inactivation as a therapeutic target. We evaluated Sarm1 deletion effects after TBI using a concussive model that causes traumatic axonal injury and progresses to CC atrophy at 10 weeks, indicating post-traumatic neurodegeneration. Sarm1 wild-type (WT) mice developed significant CC atrophy that was reduced in Sarm1 KO mice. Using electron microscopy to quantify individual axons demonstrated that Sarm1 KO preserved more intact axons and reduced damaged or demyelinated axons. MRI in live mice identified significantly reduced CC volume after TBI in Sarm1 WT mice that was attenuated in Sarm1 KO mice. MR diffusion tensor imaging detected reduced fractional anisotropy in both genotypes while axial diffusivity remained higher in Sarm1 KO mice. Immunohistochemistry revealed significant attenuation of CC atrophy, myelin loss, and neuroinflammation in Sarm1 KO mice after TBI. Functionally, TBI resulted in late-stage motor learning and sleep deficits that were ameliorated in Sarm1 KO mice. Based on these findings, Sarm1 inactivation can protect axons and white matter tracts to improve translational outcomes associated with CC atrophy and post-traumatic neurodegeneration.

scholarly journals Age, Sex and Cerebral Microbleed Effects On White Matter Degradation After Traumatic Brain Injury

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 886-887
Author(s):  
Andrei Irimia ◽  
Ammar Dharani ◽  
Van Ngo ◽  
David Robles ◽  
Kenneth Rostowsky
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Diffusion Tensor ◽  
Diffuse Axonal Injury ◽  
Principal Component ◽  
Older Age ◽  
Analysis Of Covariance ◽  
Future Research ◽  
Cerebral Microbleed

Abstract Mild traumatic brain injury (mTBI) affects white matter (WM) integrity and accelerates neurodegeneration. This study assesses the effects of age, sex, and cerebral microbleed (CMB) load as predictors of WM integrity in 70 subjects aged 18-77 imaged acutely and ~6 months after mTBI using diffusion tensor imaging (DTI). Two-tensor unscented Kalman tractography was used to segment and cluster 73 WM structures and to map changes in their mean fractional anisotropy (FA), a surrogate measure of WM integrity. Dimensionality reduction of mean FA feature vectors was implemented using principal component (PC) analysis, and two prominent PCs were used as responses in a multivariate analysis of covariance. Acutely and chronically, older age was significantly associated with lower FA (F2,65 = 8.7, p < .001, η2 = 0.2; F2,65 = 12.3, p < .001, η2 = 0.3, respectively), notably in the corpus callosum and in dorsolateral temporal structures, confirming older adults’ WM vulnerability to mTBI. Chronically, sex was associated with mean FA (F2,65 = 5.0, p = 0.01, η2 = 0.1), indicating males’ greater susceptibility to WM degradation. Acutely, a significant association was observed between CMB load and mean FA (F2,65 = 5.1, p = 0.009, η2 = 0.1), suggesting that CMBs reflect the acute severity of diffuse axonal injury. Together, these findings indicate that older age, male sex, and CMB load are risk factors for WM degeneration. Future research should examine how sex- and age-mediated WM degradation lead to cognitive decline and connectome degeneration after mTBI.

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