Repeated mild brain injuries result in cognitive impairment in B6C3F1 mice

S. Michelle DeFord, Margaret S. Wilson, Ann C. Rice, Tobias Clausen, Lee K. Rice, Anya Barabnova, Ross Bullock, Robert J. Hamm

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

Experimental investigations of single mild brain injury (SMI) show relatively little resultant cognitive impairment. However, repeated mild brain injuries (RMI), as those sustained by athletes (e.g., football, hockey, and soccer players) may have cumulative effects on cognitive performance and neuropathology. Numerous clinical studies show persistent, latent, and long-term consequences of RMI, unlike the episodic nature of SMI. The nature of repeated traumatic brain injury (TBI) introduces confounding factors in invasive and even semiinvasive animal models of brain injury (e.g., scar formation). Thus, the present study characterizes SMI and RMI in a noninvasive mouse weight drop model and the cumulative effects of RMI on cognitive performance. Investigation of drop masses and drop distances revealed masses of 50, 100, and 150 g dropped from 40 cm resulted in 0% mortality, no skull fracture, and no difference in acute neurological assessment following sham injury, SMI, or RMI. Cumulative effects of RMI were examined following four mild brain injuries 24 h apart induced by 50-, 100-, or 150-g masses dropped from 40 cm through histological measures, mean arterial pressure, and measures of complex/spatial learning. RMI produced no overt cell death within the cortex or hippocampus, no evidence of blood-brain barrier compromise, and no significant change in mean arterial pressure. Following testing in the Morris water maze (MWM) on days 7-11 after initial injury, mice in the RMI 100-g and RMI 150-g groups had significantly longer MWM goal latencies compared to sham, SMI 150-g, and RMI 50-groups. Additionally, the evident cognitive deficit manifested in the absence of observed cell death. This is the first study to show complex/spatial learning deficits following RMI, similar to the visual/spatial perception and planning deficits observed in clinical studies.

Original languageEnglish (US)
Pages (from-to)427-438
Number of pages12
JournalJournal of neurotrauma
Volume19
Issue number4
DOIs
StatePublished - Jan 1 2002

Keywords

  • Cognitive performance
  • Concussion
  • Head injury
  • Mild brain injury
  • Repeated brain injury
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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    DeFord, S. M., Wilson, M. S., Rice, A. C., Clausen, T., Rice, L. K., Barabnova, A., Bullock, R., & Hamm, R. J. (2002). Repeated mild brain injuries result in cognitive impairment in B6C3F1 mice. Journal of neurotrauma, 19(4), 427-438. https://doi.org/10.1089/08977150252932389