RESUMO
BACKGROUND: Inhibition of calpain activity provides neuroprotection in multiple central nervous system injury, but the role and mechanism of calpain in subarachnoid hemorrhage (SAH) remain unclear. This study was undertaken to determine the effects of inhibition of calpain on neurological deficit and neuronal apoptosis following experimental SAH. METHODS: The endovascular perforation model of SAH was produced in male Sprague-Dawley rats. Rats were administered calpeptin 50 µg, intracerebroventricular injection, 30 minutes before induction of SAH. After 72 hours, the method of Evans blue dye extravasation and wet/dry method were used for determination of blood-brain barrier permeability and brain edema, Western blot analysis and immunohistological staining were used to evaluate neuronal apoptosis. RESULTS: The intracellular Ca2+ level and calpain activity was significantly elevated in basal cortex after SAH. Calpain inhibitor calpeptin reduces brain water content and Evans blue dye extravasation, improves neurobehavioral deficits after SAH. Importantly, calpeptin treatment significantly reduces activation of caspase-3, caspase-9, caspase-12 and poly ADP ribose polymerase and the number of apoptotic neurons in basal cortex after SAH. CONCLUSION: The present study suggested that calpeptin is neuroprotective in early brain injury after SAH through antiapoptotic effect.
