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Objective: To investigate the protective effect of combined pretreatment of edaravone and propofol on cerebral cortex with ischemia/reperfusion (I/R) injury and its therapeutic window., Methods: Sprague Dawley (SD) rat brain cortex cells harvested within 24 hours of birth were cultured in vitro for 7 days. The cells were then divided into blank control group, glutamate injury group, 24-hour drug precondition control group, and 24-, 2-, 0-hour drug precondition groups according to random number table. The nerve cells in each pretreatment group were cultured in medium containing 100 μmol/L of edaravone and 3 mg/L of propofol 24, 2, or 0 hour before glutamate damage (200 μmol/L for 0.5 hour). Nerve cell survival or damage was determined by methyl thiazolyl tetrazolium (MTT), lactate dehydrogenase (LDH) leakage rate, and nerve cell Na+-K+-ATPase activity. The oxidation and anti-oxidation ability of nerve cells was observed by determining superoxide dismutase (SOD) activity (xanthine oxidase), malondialdehyde (MDA) content (thiobarbituric acid). Nerve apoptosis was detected by flow cytometry., Results: Compared with blank control group, in the glutamate injury group, nerve cell survival rate [(62.2±23.4)% vs. (90.5±14.8)%], the activity of SOD (U/ml: 6.864±2.872 vs. 29.569±3.684), Na+-K+-ATPase activity [U×mg(-1)×h(-1): 0.318±0.146 vs. 0.636±0.168] were significantly decreased, and rate of neuronal apoptosis [(9.4±0.7)% vs. (6.1±0.2)%], the content of MDA (nmol/ml: 0.515±0.101 vs. 0.294±0.105), LDH leakage rate [(41.2±1.6)% vs. (36.8±4.6)%] were significantly increased (P<0.05 or P<0.01). Compared with glutamate injury group, the cell survival rate and the activity of SOD and Na+-K+-ATPase were significantly increased in the drug pretreatment groups, and apoptosis rate, MDA content, and LDH leakage rate were significantly decreased with time-department, and effect in the 24-hour pretreatment group was most significant [survival rate of cell: (89.2±30.3)% vs. (62.2±23.4)%, SOD activity (U/ml): 17.780±4.514 vs. 6.864±2.872, Na+-K+-ATPase activity [U×mg(-1)×h(-1)]: 0.541±0.052 vs. 0.318±0.146, the rate of cell apoptosis: (6.7±0.4)% vs. (9.4±0.7)%, the content of MDA (nmol/ml): 0.319±0.101 vs. 0.515±0.101, LDH leakage rate: (37.2±1.4)% vs. (41.2±1.6)%, all P<0.01]., Conclusion: The synergistic protective effect of pretreatment with edaravone combined with propofol on neonatal rat brain cortex cells with I/R injury in vitro was evident; and 24-hour pretreatment is the best time window of protection for the cerebral neurons.

Objective: To study the effect of nerve growth factor (NGF) pretreatment on apoptosis of neurons and the expression of Bcl-2 and Bax protein in cerebral cortex and hippocampus CA1 zone following global cerebral ischemia/reperfusion (I/R) injury in gerbils and to explore the mechanism of protection and the best time window of NGF pretreatment., Methods: Global cerebral I/R injury model was induced by occlusion of bilateral carotid arteries. NGF was injected into the lateral ventricle. Thirty gerbils were randomly divided into five groups, with six animals in each: sham operation group (A group), I/R injury group (B group), NGF pretreatment 12, 24 and 48 hours groups (C, D and E group). Gerbils in all groups were sacrificed after being subjected to 20 minutes of cerebral ischemia followed by 72 hours reperfusion, except A group. Neural apoptosis was identified by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and immunohistochemistry was used to detect the expression of Bcl-2 and Bax protein in cerebral cortex and hippocampus CA1 zone., Results: Compared with B group, the number of apoptotic neurons and the expression of Bax positive cells in NGF pretreatment groups were decreased significantly (all P<0.05), while the expression of Bcl-2 positive cells was increased significantly (all P<0.05). The apoptotic rate in cerebral cortex and hippocampus CA1 zone and expression rate of Bax protein positive cells were the lowest, but the expression rate of Bcl-2 protein positive cells was the highest at 48 hours., Conclusion: NGF pretreatment can significantly decrease the neuronal apoptosis of the cerebral I/R injury in gerbils, and the best time window of NGF pretreatment is 48 hours. The mechanism of protection may be related to induction of Bcl-2 protein expression and inhibition of Bax protein expression by NGF pretreatment, thereby preventing neuronal apoptosis.