scholarly journals A common neural signature of brain injury in concussion and subconcussion

2019 ◽  
Vol 5 (8) ◽  
pp. eaau3460 ◽  
Author(s):  
Adnan A. Hirad ◽  
Jeffrey J. Bazarian ◽  
Kian Merchant-Borna ◽  
Frank E. Garcea ◽  
Sarah Heilbronner ◽  
...  
Keyword(s):  
White Matter ◽  
Longitudinal Design ◽  
Chronic Traumatic Encephalopathy ◽  
Structural Mri ◽  
White Matter Injury ◽  
White Matter Integrity ◽  
Head Impacts ◽  
Blood Brain Barrier Disruption ◽  
Brain Barrier Disruption ◽  
Prospective Longitudinal

The midbrain is biomechanically susceptible to force loading from repetitive subconcussive head impacts (RSHI), is a site of tauopathy in chronic traumatic encephalopathy (CTE), and regulates functions (e.g., eye movements) often disrupted in concussion. In a prospective longitudinal design, we demonstrate there are reductions in midbrain white matter integrity due to a single season of collegiate football, and that the amount of reduction in midbrain white matter integrity is related to the amount of rotational acceleration to which players’ brains are exposed. We then replicate the observation of reduced midbrain white matter integrity in a retrospective cohort of individuals with frank concussion, and further show that variance in white matter integrity is correlated with levels of serum-based tau, a marker of blood-brain barrier disruption. These findings mean that noninvasive structural MRI of the midbrain is a succinct index of both clinically silent white matter injury as well as frank concussion.

Longitudinal Changes in Resting State Connectivity and White Matter Integrity in Adolescents With Sports-Related Concussion

2018 ◽  
Vol 24 (8) ◽  
pp. 781-792 ◽  
Author(s):  
Donna L. Murdaugh ◽  
Tricia Z. King ◽  
Binjian Sun ◽  
Richard A. Jones ◽  
Kim E. Ono ◽  
...  
Keyword(s):  
White Matter ◽  
Acute Phase ◽  
Resting State ◽  
Diffusion Tensor ◽  
Longitudinal Design ◽  
White Matter Integrity ◽  
Control Group ◽  
Prospective Longitudinal ◽  
The Impact

AbstractObjectives: The aim of this study was to investigate alterations in functional connectivity, white matter integrity, and cognitive abilities due to sports-related concussion (SRC) in adolescents using a prospective longitudinal design. Methods: We assessed male high school football players (ages 14–18) with (n=16) and without (n=12) SRC using complementary resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) along with cognitive performance using the Immediate Post-Concussive Assessment and Cognitive Testing (ImPACT). We assessed both changes at the acute phase (<7 days post-SRC) and at 21 days later, as well as, differences between athletes with SRC and age- and team-matched control athletes. Results: The results revealed rs-fMRI hyperconnectivity within posterior brain regions (e.g., precuneus and cerebellum), and hypoconnectivity in more anterior areas (e.g., inferior and middle frontal gyri) when comparing SRC group to control group acutely. Performance on the ImPACT (visual/verbal memory composites) was correlated with resting state network connectivity at both time points. DTI results revealed altered diffusion in the SRC group along a segment of the corticospinal tract and the superior longitudinal fasciculus in the acute phase of SRC. No differences between the SRC group and control group were seen at follow-up imaging. Conclusions: Acute effects of SRC are associated with both hyperconnectivity and hypoconnectivity, with disruption of white matter integrity. In addition, acute memory performance was most sensitive to these changes. After 21 days, adolescents with SRC returned to baseline performance, although chronic hyperconnectivity of these regions could place these adolescents at greater risk for secondary neuropathological changes, necessitating future follow-up. (JINS, 2018, 24, 781–792)

Arterial Stiffness Is Associated with White Matter Disruption and Cognitive Impairment: A Community-Based Cohort Study

2021 ◽  
Vol 80 (2) ◽  
pp. 567-576
Author(s):  
Fei Han ◽  
Fei-Fei Zhai ◽  
Ming-Li Li ◽  
Li-Xin Zhou ◽  
Jun Ni ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
Arterial Stiffness ◽  
Cognitive Decline ◽  
Sex Education ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
White Matter Injury ◽  
White Matter Integrity ◽  
Cross Sectional

Background: Mechanisms through which arterial stiffness impacts cognitive function are crucial for devising better strategies to prevent cognitive decline. Objective: To examine the associations of arterial stiffness with white matter integrity and cognition in community dwellings, and to investigate whether white matter injury was the intermediate of the associations between arterial stiffness and cognition. Methods: This study was a cross-sectional analysis on 952 subjects (aged 55.5±9.1 years) who underwent diffusion tensor imaging and measurement of brachial-ankle pulse wave velocity (baPWV). Both linear regression and tract-based spatial statistics were used to investigate the association between baPWV and white matter integrity. The association between baPWV and global cognitive function, measured as the mini-mental state examination (MMSE) was evaluated. Mediation analysis was performed to assess the influence of white matter integrity on the association of baPWV with MMSE. Results: Increased baPWV was significantly associated with lower mean global fractional anisotropy (β= –0.118, p < 0.001), higher mean diffusivity (β= 0.161, p < 0.001), axial diffusivity (β= 0.160, p < 0.001), and radial diffusivity (β= 0.147, p < 0.001) after adjustment of age, sex, and hypertension, which were measures having a direct effect on arterial stiffness and white matter integrity. After adjustment of age, sex, education, apolipoprotein E ɛ4, cardiovascular risk factors, and brain atrophy, we found an association of increased baPWV with worse performance on MMSE (β= –0.093, p = 0.011). White matter disruption partially mediated the effect of baPWV on MMSE. Conclusion: Arterial stiffness is associated with white matter disruption and cognitive decline. Reduced white matter integrity partially explained the effect of arterial stiffness on cognition.

scholarly journals Multiple Factors Involved in the Pathogenesis of White Matter Lesions

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jing Lin ◽  
Dilong Wang ◽  
Linfang Lan ◽  
Yuhua Fan
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
White Matter ◽  
Genetic Factors ◽  
Subsequent Development ◽  
White Matter Lesions ◽  
Blood Brain Barrier Disruption ◽  
Fluid Attenuated Inversion Recovery ◽  
Cerebral Blood Flow Autoregulation ◽  
Brain Barrier Disruption

White matter lesions (WMLs), also known as leukoaraiosis (LA) or white matter hyperintensities (WMHs), are characterized mainly by hyperintensities on T2-weighted or fluid-attenuated inversion recovery (FLAIR) images. With the aging of the population and the development of imaging technology, the morbidity and diagnostic rates of WMLs are increasing annually. WMLs are not a benign process. They clinically manifest as cognitive decline and the subsequent development of dementia. Although WMLs are important, their pathogenesis is still unclear. This review elaborates on the advances in the understanding of the pathogenesis of WMLs, focusing on anatomy, cerebral blood flow autoregulation, venous collagenosis, blood brain barrier disruption, and genetic factors. In particular, the attribution of WMLs to chronic ischemia secondary to venous collagenosis and cerebral blood flow autoregulation disruption seems reasonable. With the development of gene technology, the effect of genetic factors on the pathogenesis of WMLs is gaining gradual attention.

The effects of blood–brain barrier disruption on glial cell function in multiple sclerosis

2009 ◽  
Vol 37 (1) ◽  
pp. 329-331 ◽  
Author(s):  
Stephen McQuaid ◽  
Paula Cunnea ◽  
Jill McMahon ◽  
Una Fitzgerald
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Blood Brain Barrier ◽  
Cell Function ◽  
Brain Barrier ◽  
Blood Brain Barrier Disruption ◽  
Normal Appearing White Matter ◽  
Blood Brain ◽  
Capillary Endothelial Cells ◽  
Brain Barrier Disruption

Dysfunction of the BBB (blood–brain barrier) is a major hallmark of MS (multiple sclerosis). Studies in our laboratories over the last decade have shown that increased BBB permeability is associated with decreased expression of TJ (tight junction) proteins in brain capillary endothelial cells. Results have revealed that TJ abnormalities were most common in active lesions (42% of vessels affected), but were also present in inactive lesions (23%) and in MS normal-appearing white matter (13%). Importantly, TJ abnormality was also positively associated with leakage of the serum protein fibrinogen which has recently been shown to be an activator of microglia. TJ abnormality and the resultant vascular permeability in both lesional and non-lesional white matter may impair tissue homoeostasis, which may have effects on disease progression, repair mechanisms and drug delivery.

scholarly journals Altered oligodendroglia and astroglia in chronic traumatic encephalopathy

2020 ◽  
Author(s):  
K. Blake Chancellor ◽  
Sarah E. Chancellor ◽  
Joseph E. Duke-Cohan ◽  
Bertrand R. Huber ◽  
Thor D. Stein ◽  
...  
Keyword(s):  
White Matter ◽  
Chronic Traumatic Encephalopathy ◽  
Cell Types ◽  
Cellular Stress Response ◽  
Therapeutic Interventions ◽  
Cell Nuclei ◽  
Head Impacts ◽  
Starting Point ◽  
Cell Groups ◽  
And Control

Abstract Chronic traumatic encephalopathy (CTE) is a progressive tauopathy found in contact sport athletes, military veterans, and others exposed to repetitive head impacts (RHI)1–6. White matter atrophy and axonal loss have been reported in CTE but have not been characterized on a molecular or cellular level2,7,8. Here, we present RNA sequencing profiles of cell nuclei from postmortem dorsolateral frontal white matter from eight individuals with neuropathologically confirmed CTE and eight age- and sex-matched controls. Analyzing these profiles using unbiased clustering approaches, we identified eighteen transcriptomically distinct cell groups (clusters), reflecting cell types and/or cell states, of which a subset showed differences between CTE and control tissue. Independent in situ methods applied on tissue sections adjacent to that used in the single-nucleus RNA-seq work yielded similar findings. Oligodendrocytes were found to be most severely affected in the CTE white matter samples; they were diminished in number and altered in relative proportions across subtype clusters. Further, the CTE-enriched oligodendrocyte population showed greater abundance of transcripts relevant to iron metabolism and cellular stress response. CTE tissue also demonstrated excessive iron accumulation histologically. Astrocyte alterations were more nuanced; total astrocyte number was indistinguishable between CTE and control samples, but transcripts associated with neuroinflammation were elevated in the CTE astrocyte groups as compared to controls. These results demonstrate specific molecular and cellular differences in CTE oligodendrocytes and astrocytes and may provide a starting point for the development of diagnostics and therapeutic interventions.

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