Comparison of pre- and post-ischemic treatment of telmisartan and nimodipine combination in experimentally induced cerebral ischemia

摘要

Time dependent intervention plays a crucial role in preventing neurodegeneration after ischemic insult. The intensity of excitotoxicity is greater in the secondary reperfusion phase (2-4 h) compared to the primary occlusion phase (2 h), which could be attributed to secondary elevation of excitatory amino acids (EAA) in cerebral ischemia. In the present study, we tried to assess the neuroprotective effects of telmisartan and nimodipine (TM-NM) combination on the secondary reperfusion phase. The drug treatments were made immediately after reperfusion and their effects were compared with pre-treatment. The neuroprotective effect was studied using middle cerebral artery occlusion (MCAo) transient ischemic model in rats. On the 7th day after reperfusion, the rats were subjected to behavioral studies. The brain was dissected out on the 9th day to measure neurobiochemical alterations and for histopathological observations. The results have shown that TM-NM (5 mg/kg) attenuated the EAA release in different brain regions with partial restoration of energy levels in secondary reperfusion phase. Similarly, it normalized the behavioral alteration and the effect was comparable to pre-ischemic treatment (2.5 mg/kg). Pre-ischemic treatment of TM-NM (2.5 mg/kg) protected the neurons from ischemic reperfusion injury by energy dependent EAA regulation. It can be concluded from the study that, even though the pre- and post-treatment of TM-NM show similar results, the post-ischemic treatment of TM-NM combination is beneficial due to better EAA control. Since hypertension is the primary risk factor for stroke, clinical incidents of stroke in hypertensive patients receiving angiotensin receptor blockers (ARBs) can be further investigated to understand the present study in the clinical situation.