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Accumulation of non-erythroid a II-spectrin and calpain-cleaved a II-spectrin breakdown products in cerebrospinal ̄ uid after traumatic brain injury in rats
| Content Provider | Semantic Scholar |
|---|---|
| Author | Pike, Brian R. Flint, Jeremy Dutta, Satavisha Johnson, Erik Wang, Kevin K. W. Hayes, Ronald L. |
| Copyright Year | 2001 |
| Abstract | Although a number of increased CSF proteins have been correlated with brain damage and outcome after traumatic brain injury (TBI), a major limitation of currently tested biomarkers is a lack of speci®city for de®ning neuropathological cascades. Identi®cation of surrogate biomarkers that are elevated in CSF in response to brain injury and that offer insight into one or more pathological neurochemical events will provide critical information for appropriate administration of therapeutic compounds for treatment of TBI patients. Nonerythroid aII-spectrin is a cytoskeletal protein that is a substrate of both calpain and caspase-3 cysteine proteases. As we have previously demonstrated, cleavage of aII-spectrin by calpain and caspase-3 results in accumulation of proteasespeci®c spectrin breakdown products (SBDPs) that can be used to monitor the magnitude and temporal duration of protease activation. However, accumulation of aII-spectrin and aII-SBDPs in CSF after TBI has never been examined. Following a moderate level (2.0 mm) of controlled cortical impact TBI in rodents, native aII-spectrin protein was decreased in brain tissue and increased in CSF from 24 h to 72 h after injury. In addition, calpain-speci®c SBDPs were observed to increase in both brain and CSF after injury. Increases in the calpain-speci®c 145 kDa SBDP in CSF were 244%, 530% and 665% of sham-injured control animals at 24 h, 48 h and 72 h after TBI, respectively. The caspase-3speci®c SBDP was observed to increase in CSF in some animals but to a lesser degree. Importantly, levels of these proteins were undetectable in CSF of uninjured control rats. These results indicate that detection of aII-spectrin and aIISBDPs is a powerful discriminator of outcome and protease activation after TBI. In accord with our previous studies, results also indicate that calpain may be a more important effector of cell death after moderate TBI than caspase-3. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://cnbr.mbi.ufl.edu/Faculty/wang/Pike85TBI-CSF-SBDP-J%20Neurochem2001.pdf |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Biological Markers Brain Injuries CAPN1 gene Calpain Capn3 protein, rat Catabolism Cations Cell Death Cleaved cell Cysteine Proteases Cytoskeletal Proteins Cytoskeleton Discriminator Disintegration (morphologic abnormality) Endopeptidases Kohn–Sham equations Mike Lesser Patients Rodent SYNE2 gene Traumatic Brain Injury Tree accumulation User interface design caspase-3 dicesium N-succinimidyl 3-(undecahydrododecaboranyldithio)propionate |
| Content Type | Text |
| Resource Type | Article |
