Skip Navigation LinksHome > July 2011 - Volume 70 - Issue 7 > Repetitive Closed-Skull Traumatic Brain Injury in Mice Cause...
Text sizing:
A
A
A
Journal of Neuropathology & Experimental Neurology:
doi: 10.1097/NEN.0b013e31821f891f
Original Articles

Repetitive Closed-Skull Traumatic Brain Injury in Mice Causes Persistent Multifocal Axonal Injury and Microglial Reactivity

Shitaka, Yoshitsugu PhD; Tran, Hien T. BA; Bennett, Rachel E. BA; Sanchez, Laura; Levy, Marilyn A. BA; Dikranian, Krikor PhD; Brody, David L. MD, PhD

Collapse Box

Abstract

Repetitive mild or "concussive" traumatic brain injury (TBI) can cause substantial neurologic impairment, but the pathological features of this type of injury are not fully understood. We report an experimental model of TBI in which the closed skulls of anesthetized male C57BL/6J mice are struck with an electromagnetically controlled rubber impactor twice with an interval of 24 hours between impacts. The mice had deficits in Morris water maze performance in the first week after injury that only partially resolved 7 weeks later. By routine histology, there was no apparent bleeding, neuronal cell loss, or tissue disruption, and amyloid precursor protein immunohistochemistry demonstrated very few immunoreactive axonal varicosities. In contrast, silver stainingrevealed extensive abnormalities in the corpus callosum and bilateral external capsule, the ipsilateral cortex and thalamus, and the contralateral hippocampal CA1 stratum radiatum and stratum oriens. Electron microscopy of white matter regions demonstrated axonal cytoskeletal disruption, intra-axonal organelle compaction, and irregularities in axon caliber. Reactive microglia were observed in the same areas as the injured axons by both electron microscopy and Iba1 immunohistochemistry. Quantitative analyses of silver staining and Iba1 immunohistochemistry at multipletime points demonstrated transient cortical and thalamic abnormalities but persistent white matter pathology as late as 7 weeks after injury.Thus, prominent and long-lasting abnormalities in this TBI model were underestimated using conventional approaches. The model may be useful for mechanistic investigations and preclinical assessmentof candidate therapeutics.

© 2011 American Association of Neuropathologists, Inc

Login

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.