Cleaved-tau: a biomarker of neuronal damage after traumatic brain injury
- PMID: 15665604
- DOI: 10.1089/neu.2005.22.83
Cleaved-tau: a biomarker of neuronal damage after traumatic brain injury
Abstract
Previous studies from our laboratory indicate that traumatic brain injury (TBI) in humans results in proteolysis of neuronally-localized, intracellular microtubule associated protein (MAP)-tau to produce cleaved tau (C-tau). The present study evaluated the utility of C-tau to function as a biomarker of neuronal injury and as a biomarker for evaluating neuroprotectant drug efficacy in a controlled cortical impact model of rat TBI. Brain C-tau was determined in rats subjected to controlled cortical impact-induced mild, moderate or severe levels of TBI. A significant severity-dependent increase in C-tau levels was observed in the cortex and hippocampus (1.5-8-fold) of TBI rats compared to shams 72 h after impact. C-tau rat brain and serum time course was determined by measuring levels at 0.25, 6, 24, 48, 72 and 168 h after TBI. A significant time-dependent increase in C-tau levels was observed in ipsilateral cortex (5-16-fold) and hippocampus (2-40-fold) compared to sham animals. C-tau levels increased as early as 6 h after TBI with peak C-tau levels observed 168 h after injury. Elevated brain C-tau levels were associated with TBI-induced tissue loss, which was histologically determined. The effect of cyclosporin-A (CsA), previously demonstrated to be neuroprotective in rat TBI, on brain C-tau levels was examined. CsA (20 mg/kg i.p., 15 min and 24 h after TBI) significantly attenuated the TBI-induced increase in hippocampal C-tau levels observed in vehicle-treated animals confirming CsA's neuroprotectant effect. CsA treatment also lowered ipsilateral cortical C-tau levels, although it did not reach statistical significance. CsA's neuroprotectant effect was confirmed utilizing histologic measures of TBI-induced tissue loss. In addition, serum C-tau levels were significantly increased 6 h after TBI but not at later time points. These results suggest that C-tau is a reliable, quantitative biomarker for evaluating TBI-induced neuronal injury and a potential biomarker of neuroprotectant drug efficacy in the rat TBI model. Serum data suggests that C-tau levels are dependent both on a compromised blood-brain barrier as well as release of TBI biomarkers from the brain, which has implications for the study of human serum TBI biomarkers.
Similar articles
-
Quantification and localization of kainic acid-induced neurotoxicity employing a new biomarker of cell death: cleaved microtubule-associated protein-tau (C-tau).Neuroscience. 2003;121(2):399-409. doi: 10.1016/s0306-4522(03)00459-7. Neuroscience. 2003. PMID: 14521998
-
Cyclosporin A preserves mitochondrial function after traumatic brain injury in the immature rat and piglet.J Neurotrauma. 2011 May;28(5):763-74. doi: 10.1089/neu.2010.1635. Epub 2011 Apr 12. J Neurotrauma. 2011. PMID: 21250918 Free PMC article.
-
Matrix metalloproteinase-9 expression and protein levels after fluid percussion injury in rats: the effect of injury severity and brain temperature.J Neurotrauma. 2010 Jun;27(6):1059-68. doi: 10.1089/neu.2009.1067. J Neurotrauma. 2010. PMID: 20233042
-
Sex, sex steroids, and brain injury.Semin Reprod Med. 2009 May;27(3):229-39. doi: 10.1055/s-0029-1216276. Epub 2009 Apr 28. Semin Reprod Med. 2009. PMID: 19401954 Free PMC article. Review.
-
Biomarkers in Silent Traumatic Brain Injury.Curr Pharm Des. 2016;22(6):680-7. doi: 10.2174/1381612822666151204000458. Curr Pharm Des. 2016. PMID: 26635272 Review.
Cited by 36 articles
-
Brain Injury-Mediated Neuroinflammatory Response and Alzheimer's Disease.Neuroscientist. 2020 Apr;26(2):134-155. doi: 10.1177/1073858419848293. Epub 2019 May 16. Neuroscientist. 2020. PMID: 31092147 Free PMC article.
-
Targeting the mitochondrial permeability transition pore in traumatic central nervous system injury.Neural Regen Res. 2018 Aug;13(8):1338-1341. doi: 10.4103/1673-5374.235218. Neural Regen Res. 2018. PMID: 30106036 Free PMC article. Review.
-
Neuroprotective Effects of Cyclosporine in a Porcine Pre-Clinical Trial of Focal Traumatic Brain Injury.J Neurotrauma. 2018 Jul 24;36(1):14-24. doi: 10.1089/neu.2018.5706. Online ahead of print. J Neurotrauma. 2018. PMID: 29929438 Free PMC article.
-
The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer's Disease.Front Immunol. 2018 Apr 9;9:672. doi: 10.3389/fimmu.2018.00672. eCollection 2018. Front Immunol. 2018. PMID: 29686672 Free PMC article. Review.
-
Behavioral and pathophysiological outcomes associated with caffeine consumption and repetitive mild traumatic brain injury (RmTBI) in adolescent rats.PLoS One. 2017 Nov 6;12(11):e0187218. doi: 10.1371/journal.pone.0187218. eCollection 2017. PLoS One. 2017. PMID: 29108016 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
-
Full Text Sources
-
Other Literature Sources