Therapeutic efficacy of intraventricular cyclosporine A and methylprednisolone on a global cerebral ischemia model in rats.
ABSTRACT Cyclosporine A (CsA) with its immunosuppressive actions and methylprednisolone (MP) as a free radical scavenger were suggested together to alleviate neural tissue damage after an ischemic insult. The aim of this study was to investigate neuroprotective properties of CsA and MP in a global cerebral ischemia model.
Twenty-eight male Sprague-Dawley rats were divided randomly into four separate groups: CsA, MP, sham and control. Global cerebral ischemia was performed with the four-vessel occlusion model. After 30 minutes of ischemia, reperfusion was started with concomitant intraventricular administration of saline, MP (20 mg/kg) and CsA (10 mg/kg) into the lateral ventricle. Lipid peroxidation levels were measured from all experimental groups. Rats subjected to global cerebral ischemia exhibited a significant increase in cerebral lipid peroxide levels 6 hours after the onset of reperfusion. Both CsA and MP treatment significantly attenuated the degree of lipid peroxidation in cerebral tissues (p<0.05). Histopathological examinations of the CA1 sector of the hippocampus verified the neuroprotective properties of MP and CsA.
The results suggested the neuroprotective properties of both agents, emphasizing more potent protection against ischemia by CsA. It was proposed that CsA could have exerted this effect with the blockage of mitochondrial permeability transition (MPT) pores, which are also critical if the necrotic and apoptotic cascades of the cell are considered. MP is judged to be neuroprotective, particularly in terms of its effects on lipid peroxidation. In conclusion, CsA and MP are ascertained to be neuroprotective agents as long as they cross the blood-brain barrier.