Effect Of Batroxobin On Focal Cerebral Ischemia-reperfusion Injry Follwing Ischemic Preconditioning In The Rat

Aim Improving the ability of the brain to tolerate ischemic injury has important implications. We investigated the effect of Batroxobin on focal cerebral ischemia-reperfusion (IR) injury following ischemic preconditioning (IP) in the rat.Methods 96 adult Sprague-Dawley rats were randomized into four groups: group A (sham group, n=24); group B (IR group, n=24); group C (IP group, n=24); group D (Batroxobin plus IP group, n=24). The rats subjected to middle cerebral artery occlusion with nylon suture occlusion were injected intraperitoneally with Batroxobin before reperfusion. Neuroprotective effect of Batroxobin on IR was evaluated in terms of neural function (neurological deficit score [NDS]) and morphology (HE staining, EM, TTC staining, cerebral water content, and TUNEL assay) at 3, 6, 24, and 72 hours. In addition,immunohistochemistry and immunoblotting were used to detect C-Jun NH2-terminal kinase (JNK) and extracelluar-regulated protein kinases (ERK) expression.Results Compared with the sham group, NDS increased gradually and peaked at 72 hours in the IR group. The cerebral infarct volume ratio, necrosis, and apoptotic cell death were evident in IR-treated rats at 24 hours, and the cerebral water content peaked at 72 hours. IP significantly decreased all of above parameters compared with the IR group, and Batroxobin treatment decreased further. At a molecular basis, IR significantly increased JNK and ERK immunoreactivity and expression. IP decreased JNK but increased ERK expression, and this phenomenon was more pronounced after addition of Batroxobin.Conclusions These findings suggest that Batroxobin treatment enhances neuroprotective effect of IP against IR injury in the rat, and that this may be associated with differentiaiy regulation of ERK and JNK expression. Our observation may provide a new avenue for therapy to prevent brain damage in IR injury.