Neuroprotective effect of Cyclosporin A on the development of early brain injury in a subarachnoid hemorrhage model: a pilot study.

Cyclosporin A (CsA) has been demonstrated to be neuroprotective in ischemic and traumatic brain injuries by inhibiting mitochondrial permeability transition pore (mPTP) opening, thereby maintaining mitochondrial homeostasis and inhibiting pro-apoptotic protein release. The effects of CsA on early brain injury (EBI) after subarachnoid hemorrhage (SAH), however, have not been investigated. This study was designed to explore the effects of CsA on apoptotic signaling pathways and EBI after experimental SAH using four equal groups (n=36) of adult male SD rats, including the sham group, SAH+vehicle group, SAH+CsA2 group, and SAH+CsA10 group. The rat SAH model was induced by injection of 0.3ml non-heparinized arterial blood into the prechiasmatic cistern. In the SAH+CsA2 and SAH+CsA10 groups, a dose of 2mg/kg and 10mg/kg CsA was directly administered by intercarotid injection at 15min and again 24h after SAH induction. Cerebral tissue samples were extracted 48h after SAH. Increased expressions of Cytochrome C, apoptosis-inducing factor (AIF), and cleaved caspase-3 were observed in the cerebral cortex after SAH. Treatment with high dose (10mg/kg) CsA markedly decreased expressions of Cytochrome C, AIF, and cleaved caspase-3, and inhibited apoptosis pathways. Administration of CsA following SAH significantly ameliorated EBI, including cortical apoptosis, brain edema, blood-brain barrier (BBB) impairment, and neurobehavioral deficits. These findings suggest that early administration of CsA may ameliorate EBI and provide neuroprotection in the SAH model through potential mechanisms that include blockage of mPTP opening and inhibition of apoptotic cell death pathways.