Cathepsin B Contributes to Traumatic Brain Injury Induced Cell Death through Mitochondria-mediated Apoptotic Pathway

Tao Lu-yang

Institute of Neuroscience of Soochow University; Department of Forensic

Medicine, Medical School of Soochow University

It has been reported that lysosomal proteases play important roles in ischemic and excitotoxic neuronal cell death. Our previous study also certificated that cathepsin B expression remarkably increased after traumatic brain injury (TBI). The present study was sought to investigate the effects of a selective cathepsin B inhibitor (CBI) on cell death and behavioral deficits in our TBI model. This model was introduced with controlled cortical impact （CCI）device. We initially examined the levels of cathepsin B activity and expression, and double immunofluorescence of cathepsin B with propidium iodide (PI) following TBI. The results showed that an increase in enzymatic activity is    associated with TBI-induced increase in a mature form of cathepsin B, and cathepsin B may play a role in TBI-induced cell injury. Additionally, we found that pre-treatment with CBI remarkably attenuated TBI-induced cell death, lesion volume, motor and cognitive dysfunction. In order to analyze the mechanism of cathepsin B in cell death signaling pathway, DNA electrophoresais, Bcl-2/Bax protein levels, Bid cleavage, cytochrome c release, and caspase-3 activation were also assessed in this study. The results imply that cathepsin B contributes to TBI-induced cell death through the present programmed cell necrosis, and mitochondria-mediated apoptotic pathway.