TY - JOUR
T1 - Dendritic spine loss and chronic white matter inflammation in a mouse model of highly repetitive head trauma
AU - Winston, Charisse N.
AU - Noël, Anastasia
AU - Neustadtl, Aidan
AU - Parsadanian, Maia
AU - Barton, David J.
AU - Chellappa, Deepa
AU - Wilkins, Tiffany E.
AU - Alikhani, Andrew D.
AU - Zapple, David N.
AU - Villapol, Sonia
AU - Planel, Emmanuel
AU - Burns, Mark P.
N1 - Funding Information:
Supported by Georgetown University''s Neural Injury and Plasticity Training Program grant T32NS041218, supported by the NIH (C.N.W.; principal investigators Dr. Jean Wrathall and Dr. Kathleen Maguire-Zeiss); the National Institute of Neurological Disorders and Stroke grant R01 NS067417 (M.P.B.); a Promote Diversity in Health-Related Research supplement (M.P.B.); a donation from K.P.B. Corporation (M.P.B.); Alzheimer Society of Canada postdoctoral awards (An.N.); the Canadian Institute of Health Research grants MOP-106423 and PCN-102993 (E.P.); Fonds de Recherche en Santé du Québec grants 16205 and 20048 (E.P.); and the Natural Sciences and Engineering Research Council of Canada grant 354722 (E.P.).
Publisher Copyright:
© Copyright 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Mild traumatic brain injury (mTBI) is an emerging risk for chronic behavioral, cognitive, and neurodegenerative conditions. Athletes absorb several hundred mTBIs each year; however, rodent models of repeat mTBI (rmTBI) are often limited to impacts in the single digits. Herein, we describe the effects of 30 rmTBIs, examining structural and pathological changes in mice up to 365 days after injury. We found that single mTBI causes a brief loss of consciousness and a transient reduction in dendritic spines, reflecting a loss of excitatory synapses. Single mTBI does not cause axonal injury, neuroinflammation, or cell death in the gray or white matter. Thirty rmTBIs with a 1-day interval between each mTBI do not cause dendritic spine loss; however, when the interinjury interval is increased to 7 days, dendritic spine loss is reinstated. Thirty rmTBIs cause white matter pathology characterized by positive silver and Fluoro-Jade B staining, and microglial proliferation and activation. This pathology continues to develop through 60 days, and is still apparent at 365 days, after injury. However, rmTBIs did not increase β-amyloid levels or tau phosphorylation in the 3xTg-AD mouse model of Alzheimer disease. Our data reveal that single mTBI causes a transient loss of synapses, but that rmTBIs habituate to repetitive injury within a short time period. rmTBI causes the development of progressive white matter pathology that continues for months after the final impact.
AB - Mild traumatic brain injury (mTBI) is an emerging risk for chronic behavioral, cognitive, and neurodegenerative conditions. Athletes absorb several hundred mTBIs each year; however, rodent models of repeat mTBI (rmTBI) are often limited to impacts in the single digits. Herein, we describe the effects of 30 rmTBIs, examining structural and pathological changes in mice up to 365 days after injury. We found that single mTBI causes a brief loss of consciousness and a transient reduction in dendritic spines, reflecting a loss of excitatory synapses. Single mTBI does not cause axonal injury, neuroinflammation, or cell death in the gray or white matter. Thirty rmTBIs with a 1-day interval between each mTBI do not cause dendritic spine loss; however, when the interinjury interval is increased to 7 days, dendritic spine loss is reinstated. Thirty rmTBIs cause white matter pathology characterized by positive silver and Fluoro-Jade B staining, and microglial proliferation and activation. This pathology continues to develop through 60 days, and is still apparent at 365 days, after injury. However, rmTBIs did not increase β-amyloid levels or tau phosphorylation in the 3xTg-AD mouse model of Alzheimer disease. Our data reveal that single mTBI causes a transient loss of synapses, but that rmTBIs habituate to repetitive injury within a short time period. rmTBI causes the development of progressive white matter pathology that continues for months after the final impact.
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U2 - 10.1016/j.ajpath.2015.11.006
DO - 10.1016/j.ajpath.2015.11.006
M3 - Article
C2 - 26857506
AN - SCOPUS:84958905881
VL - 186
SP - 552
EP - 567
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 3
ER -