| Background: Hypoxic-ischemic brain damage (HIBD) is the main complication of neonatal asphyxia, which is a severe state with high mortality. It often causes neonatal death and development disturbance in neural system. To seek effective treatment is one of the major objections in neonatal researches. C-AMP response element binding protein is one of major medium for neuronal survival in brain ischemia. After ischemia or glutamicacid pretreatment, the intra-flow of Ca2+ controlled by glutamicacid NMDA receptor and following activation of CaMII-IV will phosphorylate CREB . Phosphorylation of c-AMP response element binding protein (p-CREB) provides neuroprotective signals in times of cellular stress such as ischemia. It is important to explore the clinic medication from the standpoint of CREB. However, monosialotertrahexosylganglioside (GM1), one of the glutamicacid receptor abuse dependent antagonists (RADA), which can selectively inhibit the pathophysiological changes induced by glutamicacid. RADA without disturbing the normal information transmissions of glutamicacid receptor has a potential application. Our research of the GM1 effect on p-CREB was to evaluate the protection of GM1 to provide the theoretical foundation for clinical treatments in neonatalHIE.Aim: To study the expression of phosphorylated cyclic AMP response element binding protein (p-CREB) in hippocampus (CAl) of neonatal hypoxic-ischemic rats and effects of GM1 on it. Methods: 108SD 7-day-old rats weighting 12-16 g were randomly divided into three groups: control group (control, n=36), hypoxic-ischemia group (HI, n=36), and hypoxic-ischemia with GM1 group (GM1, n=36). After anesthesia with aether, the right common carotid artery of each rat was exposed, isolated from nerve and vein, and ligated with double surgical silk. One-hour after recovery, they were placed in an airtight gassing chamber and exposed to a mixture of 92% nitrogen and 8% oxygen for two hours. The oxygen concentration was maintained at (8?.5)% by oxo-concentration monitoring instrument. The control group was only being dissociated of the right common carotid artery without ligation. The intraperitonial gangliosides (GM1 30mg/Kg ) administrated 30min in GM1 group before and immediately after surgery. At 1 h, 4h, 12h, 24h, 48h, 72h after hypoxic-ischemia, the rats were decapitated and their brains were rapidly removed and fixed for 1h in 4% paraformaldehyde in PB at 4C. Levels of p-CREB and apoptotic neuron in CA1 of hippocampus were detected respectively by immunohistochemistry and TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling).Results: In neonatal rat, p-CREB in CAl was mainly distributed in pyramid neuron. The p-CREB level in the CAl of control group has no difference at different times (P>0.05). After hypoxic-ischemia, the p-CREB levels in the CAl of HI group increase transiently and then decrease quickly. There is statistical difference compared with thecontrol group (P<0.05). In GM1 group , the p-CREB levels in the CAl increase transiently and then decrease quickly, compared with control group (P<0.05) ,but there is no significant difference as compared HI group with GM1 group (P>0.05).Few neuronal apoptosis was detected in control group. Neuronal apoptosis in CAl began at 4 hours after hypoxic-ischemia, peaked at 24 hours after HI. Positive cells of neuronal apoptosis detected by TUNEL in GM1 group decreased significantly, compared with HI group (P<0.05) . But neuronal apoptosis was more significantly than control group(P<0.05). It suggests that the drugs of GM1 could partly decrease neuronal apoptosis. Conclusion: These results indicate that1. In neonatal rat, p-CREB was mainly expressed in pyramid neurons in CAl. Such moderate activation of CREB may be necessary for the basal maintenance of signal transduction to ensure neuronal integrity.2. P-CREB level in the CAl after hypoxic-ischemia increases transiently and then decreases quickly, which may be related to the characteristics of EAA releasing phase, the features a...
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