Abstract：Objective The activation of NMDA receptor plays an important role in the pathophysiological process of hypoxic ischemic brain damage (HIBD). This paper aims at studying the mechanism of the protective effect of NMDA receptor antagonist MK 801 against HIBD. Methods Thirty 7 day old SD rats were randomly assigned into Normal control, HIBD and HIBD+MK 801 groups (n=10 each). The rats in the latter two groups were kept in an environment of 8% O 2 after their right common carotid arteries were ligated. The rats in the HIBD+MK 801 group were injected with 0.3 mg/kg of MK 801 intraperitoneally before hypoxia exposure. All rats were sacrificed by decapitation immediately hypoxia and ischemia (HI). The single cell suspension of each hemisphere was prepared and the mitochondrial membrane potential (△Ψm) and intracellular free calcium ([Ca 2+ ]i) of the brain cell suspension were measured by flow cytometry and fluorescence spectrophometer respectively. Results Compared to the Normal control group, the △Ψm levels of both hemispheres and the right to left △Ψm ratio in the HIBD group decreased significantly and the [Ca 2+ ]i level increased significantly (P< 0.05 or 0.01 ); compared to the HIBD group, the △Ψm level and the right to left △Ψm ratio in the HIBD+MK 801 group increased significantly (P< 0.05 or 0.01 ). There was no difference in the right to left [Ca 2+ ]i ratio between the HIBD and the HIBD+MK 801 groups. Conclusions MK 801 may protect the neonatal brain from hypoxic ischemic damage by improving the brain cell mitochondrial function through the "NMDA receptor other △Ψm" pathway, but not through the "NMDA receptor [Ca 2+ ]i △Ψm" pathway.
HEI Meng-Yan,KUANG Shou-Jin,Inderjeet Bhatia et al. Mechanisms of the protective effect of MK2801 against hypoxic-ischemic brain damage[J]. CJCP, 2004, 6(2): 81-84.
