Neuroprotective effects of anti-tumor necrosis factor-alpha antibody on apoptosis following subarachnoid hemorrhage in a rat model

Recent studies have emphasized the importance of apoptosis in subarachnoid hemorrhage (SAH) and the subsequent early brain injury. However, the apoptotic pathways induced by SAH in different brain regions are not fully understood. We investigated gene expression levels of classical apoptosis-related molecules (caspase-3, bax, and bcl-2) following SAH in the hippocampus of male Wistar rats. Temporally specific changes were found in caspase-3 and bax messenger RNA only. Interestingly, we found increased expression of bax, but not caspase-3, in the prefrontal cortex, which indicates different molecular mechanisms of apoptosis in distinct brain regions. Most important, changes in expression were reversed by functional blockade of tumor necrosis factor-alpha, which has a critical role in brain injury. In addition, we found that apoptosis induced by SAH may be associated with a relative elevation of pro-brain derived neurotrophic factor. (C) 2011 Elsevier Ltd. All rights reserved.