Effects of Different Degrees of Hypoxia-ischemia on Neuronal Apoptosis and Astrocyte Proliferation in Neonatal Rats / 中国医科大学学报

ABSTRACT

Objective To explore the effects of different degrees of hypoxia-ischemia(HI)on neuronal apoptosis and astrocyte proliferation in neonatal rats.Methods A total of 72 rat pups aged 7 days were randomly divided into 3 groups(n=24 each group)sham operated group,mild HI group,and severe HI group.The rats were subjected to right carotid artery occlusion and exposed to a hypoxic gas mixture (8% oxygen and 92% nitrogen)for 40 minutes at 34.5℃ in mild HI group and for 65 minutes at 35.5℃ in severe HI group.The expression of glial fibrillary acidic protein(GFAP)was detected by immunohistochemistry,and TUNEL method was performed to observe the proliferation of astrocytes and the neuronal apoptosis.Results Compared with sham operated group,the number of GFAP-positive cells signifiantly increased throughout the cortex and white matter in the ischemic hemisphere 48 hours(P＜0.01)and 1 week(P＜0.05)after mild HI,and in some areas the increase continued until week 4(P＜0.05).The number of GFAP-positive astrocytes in the cortex and white matter was signficantly higher in severe HI group than in mild HI group(P＜0.05)and sham operated group(P＜0.01)48 hours and 1 week after severe HI,but the increase was not detectable at week 4.Compared with sham operated group,the number of TUNEL-positive cells in the subcortical white matter in the ischemic hemisphere signficantly increased in mild HI group 48 hours,1 week,and 4 weeks following a mild HI insult(P＜0.05),but no signficant difference in the number of TUNEL-positive cells in the cortex was found.Following a severe HI insult,the number of TUNEL-positive cells in the cortex and white matter in the ischemic hemisphere significantly increased at 48 hours(P＜0.01),and in peri-infarct regions the number of TUNEL-positive cells increased until weeks 1 and 4(P＜0.05).Conclusion Mild HI causes neuronal apoptosis mainly in subcortical white matter and prolonged proliferation of astrocytes.Severe HI is associated with widespread neuronal apoptosis in the ischemic hemisphere,and the proliferation of astrocytes is rapid and prominent after severe HI.