The neuroprotection of cinepazide maleate on acute cerebral ischemic brain in rats: a proton magnetic spectroscopy study

Abstract

Objective To dynamically monitor the effect of Cinepazide maleate (CM) on ischemic region of the brain and to elucidate the neuroprotection of CM on acute cerebral ischemic rat model and related mechanisms. Methods The rat model of acute brain ischemia-reperfusion was established with tighting threads. They were randomly divided into ischemia-reperfusion group and CM treatment group(n=8 in each group). Rats in CM treatment group were given 3 mg / kg CM by caudal intravenous injection immediately after brain ischemia-reperfusion. T2 weighted imaging(T2WI) and proton magnetic resonance spectroscopy (1HMRS) were performed before operation and at 6 hours, 24 hours and 3 days after reperfusion. Results At 6 h, 24 h and 3 d after operation there was no difference for areas of cerebral ischemia on T2WI between 2 groups. The values of N-acetylaspartate(NAA) (Phosphocreatine(PCr) + Creartine(Cr)) in ischemia-reperfusion group rats were (1.53±0.20), (0.50 ±0.17), (0.44±0.13), (0.40±0.10) before operation and at 6 h, 24 h, 3 d after operation, respectively. And in CM treatment group the values of NAA /(PCr+ Cr) were (1.44±0.22), (0.68±0.13), (0.61±0.10), (0.53±0.09) at the same time points. The values of lactate(Lac)/(PCr+ Cr) in ischemia-reperfusion group were (0.03±0.01), (1.10±0.28), (1.30±0.23), (1.23±0.19) before operation and at 6 h, 24 h, 3 d after operation, respectively. And in CM treatment group the values of Lac/(PCr+ Cr) were (0.02±0.01), (0.85±0.25), (0.99±0.20), (0.90±0.15 )at the same time points. The rats in ischemia-reperfusion group had lower value of NAA/(PCr+ Cr)(P<0.01) and higher value of Lac/(PCr+ Cr) at all time points after operation than those before operation. Compared with rats in ischemia-reperfusion group, the value of NAA/(PCr+ Cr) increased(P<0.05) and the value of Lac/(PCr+ Cr) decreased(P<0.05)decreased significantly for CM treatment group rats. Conclusion CM treatment can decrease the intracellular accumulation of lactic acid and reduce neuronal necrosis in acute brain ischemia-reperfusion rats. Key words: Magnetic resonance spectroscopy; Cinepazide maleate; Cerebral ischemia