Scaled traumatic brain injury results in unique metabolomic signatures between gray matter, white matter, and serum in a piglet model

Traumatic brain injury (TBI) is highly prevalent in adults. TBI-related functional brain alterations have been linked with common post-TBI neurobehavioral sequelae, with unknown neural substrates. This study examined the systems-level functional brain alterations in white matter (WM) and gray matter (GM) for visual sustained-attention processing, and their interactions and contributions to post-TBI attention deficits. Task-based functional MRI data were collected from 42 adults with TBI and 43 group-matched normal controls (NCs), and analyzed using the graph theoretic technique. Global and nodal topological properties were calculated and compared between the two groups. Correlation analyses were conducted between the neuroimaging measures that showed significant between-group differences and the behavioral symptom measures in attention domain in the groups of TBI and NCs, respectively. Significantly altered nodal efficiencies and/or degrees in several WM and GM nodes were reported in the TBI group, including the posterior corona radiata (PCR), posterior thalamic radiation (PTR), postcentral gyrus (PoG), and superior temporal sulcus (STS). Subjects with TBI also demonstrated abnormal systems-level functional synchronization between the PTR and STS in the right hemisphere, hypo-interaction between the PCR and PoG in the left hemisphere, as well as the involvement of systems-level functional aberrances in the PCR in TBI-related behavioral impairments in the attention domain. The findings of the current study suggest that TBI-related systems-level functional alterations associated with these two major-association WM tracts, and their anatomically connected GM regions may play critical role in TBI-related behavioral deficits in attention domains.

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Regional Topological Aberrances of White Matter- and Gray Matter-based Functional Networks for Attention Processing may Foster Traumatic Brain Injury-Related Attention Deficits in Adults

10.1101/2021.11.30.470633 ◽

2021 ◽

Author(s):

Ziyan Wu ◽

Meng Cao ◽

Xin Di ◽

Kai Wu ◽

Yu Gao ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Gray Matter ◽

Right Hemisphere ◽

Critical Role ◽

Attention Deficits ◽

Functional Brain ◽

Behavioral Impairments ◽

The Right

ABSTRACTTraumatic brain injury (TBI) is highly prevalent in adults. TBI-related functional brain alterations have been linked with common post-TBI neurobehavioral sequelae, with unknown neural sub-strates. This study examined the systems-level functional brain alterations in white matter (WM) and gray matter (GM) for visual sustained attention processing, their interactions, and contribution to post-TBI attention deficits. Task-based functional MRI data were collected from 42 adults with TBI and 43 group-matched normal controls (NCs), and analyzed using the graph theoretic tech-nique. Global and nodal topological properties were calculated and compared between the two groups. Correlation analyses were conducted between the neuroimaging measures that showed significant between-group differences and the behavioral symptom measures in attention domain in the groups of TBI and NCs, respectively. Significantly altered nodal efficiency and/or degree in several WM and GM nodes were reported in the TBI group, including the posterior corona radiata (PCR), posterior thalamic radiation (PTR), postcentral gyrus (PoG), and superior temporal sulcus (STS). Subjects with TBI also demonstrated abnormal systems-level functional synchronization between the PTR and STS in the right hemisphere, hypo-interaction between PCR and PoG in the left hemisphere; as well as the involvement of systems-level functional aberrances in PCR in TBI-related behavioral impairments in the attention domain. Findings of the current study suggest that TBI-related systems-level functional alterations associated with these two major association WM tracts and their anatomically connected GM regions may play critical role in TBI-related behavioral deficits in attention domain.

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Faculty Opinions recommendation of Delayed increases in microvascular pathology after experimental traumatic brain injury are associated with prolonged inflammation, blood-brain barrier disruption, and progressive white matter damage.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718287628.793522264 ◽

2016 ◽

Author(s):

Robert Ruff

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Blood Brain Barrier ◽

White Matter Damage ◽

Barrier Disruption ◽

Blood Brain Barrier Disruption ◽

Microvascular Pathology ◽

Brain Barrier Disruption ◽

Experimental Traumatic Brain Injury

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

Innovation in Aging ◽

10.1093/geroni/igaa057.3272 ◽

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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Longitudinal Volumetric Changes following Traumatic Brain Injury: A Tensor-Based Morphometry Study

Journal of the International Neuropsychological Society ◽

10.1017/s1355617712000835 ◽

2012 ◽

Vol 18 (6) ◽

pp. 1006-1018 ◽

Cited By ~ 55

Author(s):

Kimberly D.M. Farbota ◽

Aparna Sodhi ◽

Barbara B. Bendlin ◽

Donald G. McLaren ◽

Guofan Xu ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Degenerative Change ◽

Extended Period ◽

Spatiotemporal Pattern ◽

Volume Loss ◽

Post Injury ◽

Cognitive Changes ◽

Brain White Matter

AbstractAfter traumatic injury, the brain undergoes a prolonged period of degenerative change that is paradoxically accompanied by cognitive recovery. The spatiotemporal pattern of atrophy and the specific relationships of atrophy to cognitive changes are ill understood. The present study used tensor-based morphometry and neuropsychological testing to examine brain volume loss in 17 traumatic brain injury (TBI) patients and 13 controls over a 4-year period. Patients were scanned at 2 months, 1 year, and 4 years post-injury. High-dimensional warping procedures were used to create change maps of each subject's brain for each of the two intervals. TBI patients experienced volume loss in both cortical areas and white matter regions during the first interval. We also observed continuing volume loss in extensive regions of white matter during the second interval. Neuropsychological correlations indicated that cognitive tasks were associated with subsequent volume loss in task-relevant regions. The extensive volume loss in brain white matter observed well beyond the first year post-injury suggests that the injured brain remains malleable for an extended period, and the neuropsychological relationships suggest that this volume loss may be associated with subtle cognitive improvements. (JINS, 2012,18, 1–13)

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Vestibular, balance, microvascular and white matter neuroimaging characteristics of blast injuries and mild traumatic brain injury: Four case reports

Brain Injury ◽

10.1080/02699052.2016.1219056 ◽

2016 ◽

Vol 30 (12) ◽

pp. 1501-1514 ◽

Cited By ~ 9

Author(s):

Ramtilak Gattu ◽

Faith W. Akin ◽

Anthony T. Cacace ◽

Courtney D. Hall ◽

Owen D. Murnane ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Mild Traumatic Brain Injury ◽

Case Reports ◽

Blast Injuries

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

Developmental Neuroscience ◽

10.1159/000369091 ◽

2015 ◽

Vol 37 (2) ◽

pp. 115-130 ◽

Cited By ~ 20

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.

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