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Clinical correlates in an experimental model of repetitive mild brain injury
Author(s) -
Mannix Rebekah,
Meehan William P.,
Mandeville Joseph,
Grant Patricia E.,
Gray Tory,
Berglass Jacqueline,
Zhang Jimmy,
Bryant John,
Rezaie Shervin,
Chung Joon Yong,
Peters Nicholas V.,
Lee Christopher,
Tien Lee W.,
Kaplan David L.,
Feany Mel,
Whalen Michael
Publication year - 2013
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.23858
Subject(s) - medicine , morris water navigation task , white matter , cognition , cognitive decline , psychology , traumatic brain injury , chronic traumatic encephalopathy , effects of sleep deprivation on cognitive performance , magnetic resonance imaging , neuroscience , pathology , poison control , psychiatry , dementia , radiology , concussion , injury prevention , disease , environmental health
Objective Although there is growing awareness of the long‐term cognitive effects of repetitive mild traumatic brain injury (rmTBI; eg, sports concussions), whether repeated concussions cause long‐term cognitive deficits remains controversial. Moreover, whether cognitive deficits depend on increased amyloid β deposition and tau phosphorylation or are worsened by the apolipoprotein E4 allele remains unknown. Here, we use an experimental model of rmTBI to address these clinical controversies. Methods A weight drop rmTBI model was used that results in cognitive deficits without loss of consciousness, seizures, or gross or microscopic evidence of brain damage. Cognitive function was assessed using a Morris water maze (MWM) paradigm. Immunostaining and enzyme‐linked immunosorbent assay (ELISA) were used to assess amyloid β deposition and tau hyperphosphorylation. Brain volume and white matter integrity were assessed by magnetic resonance imaging (MRI). Results Mice subjected to rmTBI daily or weekly but not biweekly or monthly had persistent cognitive deficits as long as 1 year after injuries. Long‐term cognitive deficits were associated with increased astrocytosis but not tau phosphorylation or amyloid β (by ELISA); plaques or tangles (by immunohistochemistry); or brain volume loss or changes in white matter integrity (by MRI). APOE4 was not associated with worse MWM performance after rmTBI. Interpretation Within the vulnerable time period between injuries, rmTBI produces long‐term cognitive deficits independent of increased amyloid β or tau phosphorylation. In this model, cognitive outcome is not influenced by APOE4 status. The data have implications for the long‐term mental health of athletes who suffer multiple concussions. Ann Neurol 2013;74:65–75