Abstract OBJECTIVE: Previous studies suggest that dexamethasome (DEX) pretreatment can reduce hypoxic-ischemic brain damage (HIBD), but the mechanism for this effect has not been identified. This study examined the effects of DXM pretreatment on NF-κB activation and neuronal apoptosis in the brain of neonatal rats with HIBD, in order to identify a possible mechanism for the protective effect of DEX pretreatment in HIBD. METHODS: Forty-two 6-day-old Sprague-Dawley (SD) rats were randomly assigned to 5 groups: Normal controls (n=8), Sham-operated (n=8), HIBD (n=8), DEX pretreated (P-DEX, n=9) and DEX treated (DEX, n=9).HIBD was induced by hypoxia exposure combined with ligation of the left common carotid artery. DEX (0.1 mg/kg) was administered to rats in the P-DEX group 24 hrs before HI and to rats in the DEX group immediately after HI. After 72 hrs of HI, the rats were sacrificed and then the brain tissues were removed. Apoptosis was examined by means of terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL). The expression of p65 protein in tissue sections was detected by immunohistochemistry. The expression of IκBα protein was measured by Western blotting. Co-localization of p65 protein expression and apoptosis was determined with double-label immunofluorescence. RESULTS: The number of p65 positive cells and apoptotic cells was greater and the expression of the IκBα protein was less in the HIBD and DEX groups (P< 0.01) when compared with the Normal control and Sham-operated groups (P< 0.01). There were fewer p65 positive cells and apoptotic cells, and the level of IκBα protein expression was greater in the P-DEX group (P< 0.01) compared with the HIBD group. There were no significant differences between the DEX and HIBD groups. In the HIBD group, the level of NF-κB activation and the extent of neuronal apoptosis were significantly correlated (r= 0.775, P< 0.01). CONCLUSIONS: The activation of NF-κB may play an important role in the development of neuronal apoptosis in neonatal rats with HIBD. The protective effects of DEX pretreatment may work through the inhibition of NF-κB activation which may then inhibit neuronal apoptosis.
PENG Tao,WANG Wei,YU Xiao-He et al. Effects of dexamethasone pretreatment on NF-κB activation and neuronal apoptosis in the brain of neonatal rats following hypoxia-ischemia[J]. 中国当代儿科杂志, 2004, 6(4): 251-255.
PENG Tao,WANG Wei,YU Xiao-He et al. Effects of dexamethasone pretreatment on NF-κB activation and neuronal apoptosis in the brain of neonatal rats following hypoxia-ischemia[J]. CJCP, 2004, 6(4): 251-255.
