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Objective: To study the protective effect of propofol precondition against glutamate (Glu) neurotoxicity to neonatal rat cerebrocortical slices., Methods: Brain slices of Sprague-Dawley (SD) rats were cultured in vitro and observed the morphologic changes. Brain slices were randomly divided into three groups: blank control group, Glu injury group (1 mmol/L Glu for 0.5 hour), propofol precondition group (20 mg/L propofol for 24 hours), each n=12. Changes in pathological and ultra-structure of cells were observed using microscope. Lactate dehydrogenase (LDH) leakage rate was measured. Meanwhile, the expression of glial fibrillary acidic protein (GFAP) was detected by immunohistochemical technology, then the positive cell were counted., Results: Cultured brain slices of cell were intact and survived well. Hematoxylin-eosin (HE) staining, electron microscopy and LDH test results showed that cerebral film neuron severely damage, gliosis, edema, LDH leakage rate in Glu injury group were significantly more severe compared with blank control group [(68.5±2.0)% vs. (16.0±2.5)%, P<0.01]. Reduce the brain slice of the propofol pretreatment group of neuronal cell jury, cell shape recovery significantly reduced LDH leakage rate compared with the Glu injury group [(38.5±2.4)% vs. (68.5±2.0)%, P<0.05]. Immunohistochemical detection of GFAP expression of Glu injury group glial cell body swelling, producing increase in the number of GFAP positive reaction strong, the number of positive cells compared with blank control group was significantly increased (50±5 cells/HP vs. 10±3 cells/HP, P<0.01). The recovery of propofol pretreatment group glial cell morphology, cell processes slender GFAP positive reaction decreased the number of positive cells compared with the Glu injury group was significantly decreased (30±4 cells/HP vs. 50±5 cells/HP, P<0.05)., Conclusion: Propofol pretreatment has protective effect against Glu injured rat cerebrocortical slices.

Objective: To explore the relationship between the levels and variability of blood glucose and the prognosis of critical patients., Methods: A prospective study was conducted. Blood glucose monitoring and prognosis observation were performed for the adult nondiabetic patients admitted in intensive care unit (ICU) from June 2011 to January 2012. Blood glucose monitoring terminal was 72 hours after admitting in ICU, prognosis was observed for 28 days after the end of turning into ICU. Acute physiology and chronic health evaluation II(APACHE II) scores when transferred into ICU and blood glucose variability [standard deviation (SD) of blood glucose, mean absolute blood glucose fluctuation amplitude (MAGE) and glycemic instability index (GLI)] were calculated. Patients were divided into death group and survival group according to the outcome, and the APACHE II score, mean blood glucose and blood glucose variability were compared between the two groups. Patients were divided into different groups based on the blood glucose, and the APACHE II score, blood glucose variability and 28-day mortality were compared among groups., Results: Total 85 cases were enrolled. Compared with survivor group (n=58), in death group (n=27), APACHE II score (28.9±6.6 vs. 23.8±5.9), mean blood glucose (11.9±2.9 mmol/L vs. 9.4±1.8 mmol/L), SD of blood glucose (3.7±1.6 mmol/L vs. 2.4±1.0 mmol/L), MAGE (0.86±0.46 mmol/L vs. 0.54±0.25 mmol/L) and GLI (255.9±232.7 vs. 111.7±110.9) were increased (all P<0.05). SD of blood glucose (4.3±1.4 mmol/L), MAGE (1.1±0.4 mmol/L), GLI (345.3±210.3) and 28-day mortality (63.6%) in blood glucose >11.1 mmol/L group (n=22) were higher than those in ≤11.1 mmol/L group (n=63, 2.3±0.9 mmol/L, 0.5±0.2 mmol/L, 91.9±91.2, 20.6%, respectively, all P<0.05) and 7.8-11.1 mmol/L group (n=52, 2.3±0.9 mmol/L, 0.5±0.2 mmol/L, 85.2±66.4, 25.0%, respectively, all P<0.05). There were no significant differences between 7.8-11.1 mmol/L group and <7.8 mmol/L group (n=11) in SD of blood glucose (2.0±0.9 mmol/L), MAGE (0.5±0.3 mmol/L), GLI (123.8±166.7) and 28-day mortality (0, all P>0.05)., Conclusion: Blood glucose variability is associated with critical patient's 28-day mortality, and may predict mortality as good as APACHE II score.

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 compare the protective effect of nerve growth factor (NGF) and edaravone (a free radical scavenger) pretreatment against cerebral ischemia/reperfusion (I/R) injury to nerve cells., Methods: Cortical neurons of Sprague-Dawley (SD) mouse aged shorter than 24 hours were cultured for 7 days, then they were randomly divided into control group, I/R group, NGF of 10, 50, 100 microg/L pretreatment groups and 100 mumol/L edaravone pretreatment group. In pretreatment groups the cells were pretreated with drugs correspondingly. After culturing for 24 hours, glutamate of 200 mumol/L was given into the culture of all groups, except control group, for half an hour. Then culture medium in all groups were renewed with ordinary culture medium, and cultures were continued for 24 hours. The survival rate (by methyl thiazolyl tetrazolium assay), the content of lactate dehydrogenase (LDH, by spectrometry) and the rate of apoptosis (by flow cytometric) were determined. The cellular shape and ultrastructure were observed by hematoxylin-eosin (HE) staining and electronic microscopy correspondingly., Results: The survival rate of nerve cells in NGF groups and edaravone group was significantly higher than that in I/R group [(0.21 + or - 0.04)%, (0.23 + or - 0.04)%, (0.21 + or - 0.04)%, (0.24 + or - 0.04)% vs. (0.19 + or - 0.04)%]. The content of LDH in culture medium and the rate of apoptosis in NGF groups and edaravone group were lower than those in I/R group (P<0.05 or P<0.01). The release rate of LDH in each group was (0.50 + or - 0.06)%, (0.46 + or - 0.07)%, (0.50 + or - 0.02)%, (0.43 + or - 0.06)% vs. (0.56 + or - 0.03)%, respectively. The rate of apoptosis in each group was (10.77 + or - 1.07)%, (10.38 + or - 0.70)%, (13.34 + or - 0.57)%, (9.99 + or - 0.77)% vs. (14.52 + or - 0.77)%, respectively. The cellular shape and ultrastructure of nerve cells in NGF groups and edaravone group were affected much less than that of I/R group. NGF of 50 microg/L pretreatment group gave the best effect among three groups. There was no significant difference between NGF 50 microg/L pretreatment group and edaravone pretreatment group., Conclusion: NGF and edaravone pretreatment 24 hours before cerebral I/R give protective effects against cerebral I/R injury. The protective effects are best in NGF of 50 microg/L pretreatment group and edaravone pretreatment group, and there is no significant difference between them.

Objective: To study the protective effects of lidocaine and nerve growth factor (NGF) pretreatment on cerebral ischemia/reperfusion (I/R) injury., Methods: Fifty-four Mongolian gerbils were randomly divided into nine groups: normal group (Group A), lidocaine control group (Group L), NGF control group (Group N), lidocaine pretreatment groups at the point of 12, 24, 48 hours (named respectively Group L12, L24, L48), NGF pretreatment groups with NGF given 12, 24, 48 hours before injury (named respectively Group N12, N24, N48), with 6 animals in each group. Except Group A, the carotid artery on both sides were occluded for 20 minutes, then they were released to allow reperfusion. Alteration of apoptosis was observed with terminal-deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and the expression of Bcl-2 and Bax was assessed by immunohistochemistry method., Results: No apoptosis, Bcl-2 and Bax were found in Group A. In lidocaine or NGF pretreatment group, the expression of Bcl-2 (Group L12: 36.60 + or - 3.31, Group L24: 34.73 + or - 1.82, Group L48: 65.17 + or - 1.53; Group N12: 35.70 + or - 1.18 , Group N24: 37.30 + or - 3.86, Group N48: 62.77 + or - 2.91) was obviously increased comparing with control group (Group L: 24.53 + or - 1.48, Group N: 25.43 + or - 1.85), but the number of the apoptosis (Group L12: 32.87 + or - 0.99, Group L24: 31.90 + or - 4.14, Group L48: 24.50 + or - 0.70; Group N12: 32.80 + or - 1.27, Group N24: 32.83 + or - 1.30, Group N48: 23.30 + or - 0.86) and Bax expression (Group L12: 33.47 + or - 1.21, Group L24: 33.70 + or - 1.20, Group L48: 24.67 + or - 2.09; Group N12: 32.17 + or - 2.21, Group N24: 31.97 + or - 1.79, Group N48: 23.27 + or - 1.20) were significantly decreased comparing with the control group (the number of the apoptosis: Group L 67.43 + or - 3.92, Group N 67.80 + or - 3.82; Bax: Group L 59.73 + or - 1.32, Group N 59.37 + or - 1.54, P<0.05 or P<0.01). In lidocaine and NGF pretreatment groups, the number of cell apoptosis and expression Bax were significantly lower at 48 hours than those at 12 hours or 24 hours, but the cell expression Bcl-2 was obviously higher (all P<0.05). However, there was no difference between lidocaine and NEG pretreatment groups at each time point in regard of the number of cell apoptosis, expression of Bcl-2 and Bax., Conclusion: Lidocaine and NGF pretreatment before cerebral I/R can alleviate I/R injury to the cerebral tissue. The protective effect was most obvious when the treatment was given 48 hours before ischemia. The mechanism may be related with an increase in expression of Bcl-2 as well as a decrease in Bax level.

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.