Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma.

TitleDendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma.
Publication TypeJournal Article
Year of Publication2016
AuteursWinston, CN, Noël, A, Neustadtl, A, Parsadanian, M, Barton, DJ, Chellappa, D, Wilkins, TE, Alikhani, AD, Zapple, DN, Villapol, S, Planel, E, Burns, MP
JournalAm J Pathol
Date Published2016 Mar
KeywordsAmyloid, Animals, Behavior, Animal, Brain Concussion, Brain Injuries, Craniocerebral Trauma, Dendritic Spines, Disease Models, Animal, Fluoresceins, Golgi Apparatus, Humans, Inflammation, Male, Maze Learning, Mice, Mice, Inbred C57BL, Recurrence, tau Proteins, Unconsciousness, White Matter

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.

Alternate JournalAm. J. Pathol.
PubMed ID26857506
PubMed Central IDPMC4816714
Grant ListR01 NS081068 / NS / NINDS NIH HHS / United States
R03 NS067417 / NS / NINDS NIH HHS / United States
T32 NS041218 / NS / NINDS NIH HHS / United States
T32NS041218 / NS / NINDS NIH HHS / United States