Effect of isoflurane postconditioning on expression of vascular endothelial growth factor in neonatal rats with hypoxic-ischemic brain injury

Abstract

Objective To investigate the effect of isoflurane postconditioning on the expression of vascular endothelial growth factor (VEGF) in neonatal rats with hypoxic-ischemic brain injury (HIBI).Methods One hundred and fifty-six 7-day-old Sprague-Dawley rats were randomly divided into 3 groups (n =52 each) using a random number table:sham operation group (S group),HIBI group,and isoflurane post-conditioning group (Ⅰ group).Brain ischemia was induced by ligation of the left common carotid artery followed by inhalation of 8％ O2 + 92％ N2 for 2 h at 37 ℃.The rats were exposed to 1％ isoflurane for 1 h (group Ⅰ) or to 30％ oxygen-70％ nitrogen for 1 h (HIBI group) starting from 2 h of hypoxia.The left common carotid artery was only separated and then the rats were exposed to 30％ oxygen and 70％ nitrogen for 1 h in S group.The rats were sacrificed at 1,2,3 and 7 days after HIBI (T1-4),and their brains on the damaged side were harvested for microscopic examination and for determination of the dead neuron counts in the hippocampi and cortex and expression of VEGF (by immunohistochemistry and Western blot).The cerebral infarct size was detected at T2.Results No cerebral infarct was observed in S group.Compared with S group,the cerebral infarct size and counts of dead neurons in the hippocampi and cortex on the damaged side at T1-4 were significantly increased,and the expression of VEGF was up-regulated in H IBI and Ⅰ groups (P ＜ 0.05).Compared with HIBI group,the cerebral infarct size and counts of dead neurons in the hippocampi and cortex on the damaged side at T1,2 were significantly decreased,and the expression of VEGF was up-regulated in Ⅰ group (P ＜ 0.05).There was no significant difference in the counts of dead neurons in the hippocampi and cortex on the damaged side and expression of VEGF between the time points in S group (P ＞ 0.05).The expression of VEGF peaked at T3 in HIBI group and T2 in Ⅰ group (P ＜ 0.05).The pathological changes of brain tissues on the damaged side were significantly attenuated in group Ⅰ as compared with HIBI group.Conclusion Isoflurane postconditioning reduces HIBI in neonatal rats possibility through upregulating the expression of VEGF in brain tissues. Key words: Isoflurane ; Ischemic postconditioning ; Hypoxia-ischemia, brain ; Infant, newborn ; Vascular endothelial growth factors