Journal
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Volume 68, Issue 3, Pages 241-249Publisher
OXFORD UNIV PRESS INC
DOI: 10.1097/NEN.0b013e3181996bfe
Keywords
Biomarker; Calpain; Cytoskeleton; Diffuse axonal injury; Spectrin; Traumatic brain injury
Categories
Funding
- National Institutes of Health [5R01HD055813-25, 5P30NS047463-05, R01 NS049175-01 A1]
- Department of Defense [DAMD17-03-1-0066, DAMD17-01-1-0765]
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Calpain-mediated degradation of the cytoskeletal protein alpha-II-spectrin has been implicated in tire pathobiology of experimental and human traumatic brain injury (TBI). Spectrin proteolysis after diffuse/widespread TBI uncomplicated by either Subtle or overt contusion and/or mass lesions, (i.e. mild to moderate TBI), has not been previously evaluated. To determine the spatiotemporal pattern and cellular localization of calpain-mediated spectrin proteolysis after diffuse/widespread TBI and the extent to which parenchymal changes in calpain-mediated spectrin proteolysis are reflected ill the cerebrospinal fluid, adult rats were subjected to a moderate midline fluid percussion injury and allowed to Survive for 3 hours to 7 days postinjury. Light and electron microscopic immunocytochemical and Western blot analyses were performed to identify the calpain-specific 145-kDa breakdown product of a-II-spectrin (SBDP145). After diffuse TBI, enhanced levels of SBDP145 immunoreactivity were observed in the neocortex, subcortical white matter, thalamus, and hippocampus. peaking between 24 and 48 hours postinjury. Immunoreactivity was localized almost exclusively to damaged axons and axonal terminal debris. Heightened levels of SBDP145 were also observed in the cerebrospinal fluid at 24 hours postinjury. These results confirm the widespread Occurrence of calpain-mediated spectrin proteolysis after diffuse TBI without contusion and support the potential utility of SBDPs as biomarkers of a diffusely injured brain.
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