Concussive brain trauma in the mouse results in acute cognitive deficits and sustained impairment of axonal function

J Neurotrauma. 2011 Apr;28(4):547-63. doi: 10.1089/neu.2010.1729.

Abstract

Concussive brain injury (CBI) accounts for approximately 75% of all brain-injured people in the United States each year and is particularly prevalent in contact sports. Concussion is the mildest form of diffuse traumatic brain injury (TBI) and results in transient cognitive dysfunction, the neuropathologic basis for which is traumatic axonal injury (TAI). To evaluate the structural and functional changes associated with concussion-induced cognitive deficits, adult mice were subjected to an impact on the intact skull over the midline suture that resulted in a brief apneic period and loss of the righting reflex. Closed head injury also resulted in an increase in the wet weight:dry weight ratio in the cortex suggestive of edema in the first 24 h, and the appearance of Fluoro-Jade-B-labeled degenerating neurons in the cortex and dentate gyrus of the hippocampus within the first 3 days post-injury. Compared to sham-injured mice, brain-injured mice exhibited significant deficits in spatial acquisition and working memory as measured using the Morris water maze over the first 3 days (p<0.001), but not after the fourth day post-injury. At 1 and 3 days post-injury, intra-axonal accumulation of amyloid precursor protein in the corpus callosum and cingulum was accompanied by neurofilament dephosphorylation, impaired transport of Fluoro-Gold and synaptophysin, and deficits in axonal conductance. Importantly, deficits in retrograde transport and in action potential of myelinated axons continued to be observed until 14 days post-injury, at which time axonal degeneration was apparent. These data suggest that despite recovery from acute cognitive deficits, concussive brain trauma leads to axonal degeneration and a sustained perturbation of axonal function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials / physiology
  • Analysis of Variance
  • Animals
  • Axonal Transport / physiology
  • Axons / pathology
  • Axons / physiology*
  • Blotting, Western
  • Brain Concussion / complications
  • Brain Concussion / pathology
  • Brain Concussion / physiopathology*
  • Cognition / physiology
  • Cognition Disorders / etiology
  • Cognition Disorders / pathology
  • Cognition Disorders / physiopathology*
  • Hippocampus / pathology
  • Hippocampus / physiopathology*
  • Male
  • Maze Learning / physiology
  • Memory, Short-Term / physiology
  • Mice
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Neurons / pathology
  • Neurons / physiology*