Abstract:

BACKGROUND: After cerebral ischemia-reperfusion, excessive excitatory amino acids can activate endogenous neural stem cells (NSCs) through N-methyl-D-aspartic acid (NMDA) receptor and can repair nerve cells by the proliferation and differentiation of endogenous NSCs but damage nerve cells by intracellular calcium overload at the same time.
OBJECTIVE: To study the effect of NMDA receptor antagonist MK-801 on the proliferation of endogenous NSCs of global cerebral ischemia-reperfusion rat hippocampus.
METHODS: The SD rats were divided into control group, operation group and different concentrations of MK-801 group (0.2, 0.4, 0.6, 0.8, 1.0, 1.2 mg/kg). The rats were first treated with lateral ventricle intubation, and 3 days later, four-vessel occlusion was used to establish global cerebral ischemia-reperfusion model, except the control group. Different doses of MK-801 were intracerebrally ventricularly injected at 30 minutes before cerebral ischemia. The same concentration of normal saline was used in control group and operation group. Immunohistochemistry and RT-PCR technique were used to detect nestin positive cells and mRNA level expression.
RESULTS AND CONCLUSION: When the concentration of MK-801 was under 0.8 mg/kg, the protein and mRNA expression of nestin was high and there was no difference between MK-801 group and operation group (P > 0.05). When the concentration of MK-801 was equal to 0.8 mg/kg, the expression of nestin gene and protein was decreased significantly with MK-801 increasing (P < 0.05). MK-801 can not only inhibit calcium overload but also has good effect on stimulating neural stem cell proliferation at the concentration of 0.6 mg/kg.