| Cerebrovascular disease is a source of mortality and profound morbidity that remains pervasive in the modern world. But effective therapeutic drug is few. Monoganglioside (GM1) is reported as a potential therapeutic drug for cerebral ischemia. To determine the protective effect and mechanism(s) of GM1 on cerebral ischemic injury, the effects of GM1 on neural injuries induced by focal cerebral ischemia in rats and by oxygen glucose deprivation in rat hippocampal slices were evaluated in this study. Influence of GM1 on expression of N-methyl-D-aspartate receptor subunits and protein kinase C were analyzed to clarify the possible mechanism. Effect of endogenous ganglioside on exitoxicity and serum deprivation injury on culture neural cell was observed as well.Part â… Protective effect and mechanism of monosialoganglionside (GM1) oninjury induced by focal cerebral ischemia and reperfusion in ratsPurpose: In the in vivo experiments, we determined whether GM1 has a protective effect on injury induced by focal cerebral ischemia and reperfusion and the possiblemechanism in rats. Methods: Middle cerebral artery (MCA) occlusion was performed to induce focal brain ischemia / reperfusion model by an intraluminal filament in SD rats. GM1 was given i.p. at different time point (5 min, 1 h and 2 h after ischemia). MCA was occluded for 1 h and the brain was reperfused for 12 h at that moment neurologic deficiency scores were assessed, and infarct volume was measured by TTC staining. Expression levels of NMD A receptor subunit NR1, NR2A and NR2B were detected by Western blot at reperfusion time points (4, 6, 24, 48 and 72 h) after cerebral ischemia. Results: (1) Relative infarct volume of was significantly smaller in the group administered 5 min after ischemia than that 2 h after ischemia or control (P < 0.01, one-way ANOVA). Relative infarct volume of in group administered 1 h after ischemia was significantly smaller than that of group 2 h after ischemia or control (P < 0.05, one-way ANOVA). There was no significant difference between relative infarct volume of group administered 2 h after ischemia and that of control (P > 0.05, one-way ANOVA). Adjusted relative infarct volume of group administered 5 min after ischemia was significantly smaller than that of group 2 h after ischemia and control (P < 0.01, one-way ANOVA). Adjusted relative infarct volume of group administered 1 h after ischemia was significantly smaller than that of 2 h after ischemia or control (P < 0.05, one-way ANOVA). There was not significant difference between adjusted relative infarct volume of group administered at 2 h after ischemia and that of control (P > 0.05, one-way ANOVA). TTC staining showed cerebral infarction at 6 h after reperfusion, and infarct volume gradually increased, and reached the peak at 12 h after reperfusion. Toluidine blue staining 6 h after reperfusion showed nerve cells degenerated and being missed in the cortical and basoganglic area of ischemic hemisphere. (2) Expression levels of NR1, NR2A and NR2B were elevated temporally 6 h after reperfusion, and came below normal levels at 48 ~ 72 h after reperfusion. GM1 given i.p. 5 min after ischemia significantly suppressed the expression of NR1 6 h after reperfusion (P < 0.05 vs control, T-test). NR1 expression of ischemic hemisphere 72 h after reperfusion was significantly lower than that of the control (P < 0.05, T-test), There was no significant difference between expression of NR1 in ischemic hemispheres of control and those accepted GM1 (5 min and 2 h after ischemia, 10 mg/kg, i.p.) (P > 0.05, T-test).Conclusion: Early used GM1 (< 1 h after ischemia) significantly reduces the cerebral infarct volume, but late used GM1 (2 h after ischemia) does not. One of the possible mechanisms for GM1 reducing cerebral infarct volume may be probably that early used GM1 can suppress temporally over-expression of NRl in the ischemic hemisphere 6 h after reperfusion and depressed-expression of NRl 72 h after reperfusion.
|
PDF Full Text Request