Clinical correlates in an experimental model of repetitive mild brain injury. Issue 1 (6th August 2013)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Annals of neurology. Volume 74:Issue 1(2013:Jul.)
• Page Start: 65
• Page End: 75
• Publication Date: 2013-08-06
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.23858
• Languages: English
• ISSNs: 0364-5134

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ana23858-sec-0001" sec-type="section"> <title>Objective</title> <p>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.</p> </sec> <sec id="ana23858-sec-0002" sec-type="section"> <title>Methods</title> <p>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).</p> </sec> <sec id="ana23858-sec-0003" sec-type="section"> <title>Results</title> <p>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). <italic>APOE4</italic> was not associated with worse MWM performance after rmTBI.</p> </sec> <sec id="ana23858-sec-0004" sec-type="section"> <title>Interpretation</title> <p>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 <italic>APOE4</italic> status. The data have implications for the long‐term mental health of athletes who suffer multiple concussions. Ann Neurol 2013;74:65–75</p> </sec> </abstract>