BACKGROUND: The disorder of energy metabolism and cerebral edema after cerebral ischemia-reperfusion are the important factors to inducecerebral ischemia-reperfusion injury. The Chinese herb, breviscapine, whose effective component is scutellarin, can prevent the activation of protein kinase C evoked by ischemia-reperfusion, relieve calcic overload and reduce the volume of ischemia infarcted focus volume, and then alleviate cerebral ischemia-reperfusion injury. But what are the influences of breviscapine on energy metabolism and cerebral edema after cerebral ischemia-reperfusion?OBJECTIVE: To observe the effects of breviscapine parenteral solution on energy metabolism and cerebral edema after cerebral ischemia-reperfusion in gerbils.DESIGN: A randomized control trial.SETTING: Affiliated Hospital of Jining Medical College, Jiangsu Provincial Key Laboratory of Anesthesiology, Affiliated Hospital of Xuzhou Medical College.MATERIALS: The experiment was carried out in the Jiangsu Provincial Key Laboratory of Anesthesiology Between February and August 1999. Seventy-two male gerbils were used.METHODS: The gerbils were randomly divided into sham-operated group (n=8), normothermia control group (n=32) and breviscapine group (n=32).According to the reperfused time, the normothermia control group and breviscapine group were divided into 4 subgroups with 8 gerbils in each subgroup: 0, 10, 30 and 60-minute reperfusion groups. The gerbils in the normothermia control group and breviscapine group were made into models of forebrain ischemia reperfusion, treated with ischemia for 10 minutes. In the sham-operated group, only bilateral common carotid arteries were freed but not occluded. In the breviscapine group, the gerbils were given intraperitoneal injection of breviscapine psrenteral solution (90 mg/kg) at 15 minutes before ischemia. The gerbils in the sham-operated group and normothermia control group were treated with saline of the same volume. The brain water was determined by drying electrothermostat. The contents of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine phosphate (AMP) in hippocampus were determined with high performance liquid chromatography and ultraviolet detector.MAIN OUTCOME MEASURES: ① ATP, ADP and AMP contents in hippocampus; ② Water contents in cerebral cortex.RESULTS: All the 72 gerbils were involved in the analysis of results without deletion. ① ATP, ADP and AMP contents in hippocampus: At 0, 10, 30 and 60 minutes after reperfusion, ATP and adenine nucleotide pool contents in hippocampal tissue in the normothermia control group were obviously decreased, the ATP contents were 68%, 56%, 49% and 50% of those in the sham-operated group respectively (P ＜ 0.01), and adenine nucleotide pool contents were 62%, 50%, 51% and 52% of those in the sham-operated group respectively (P ＜ 0.01). The ATP contents at each time point in the breviscapine group were 84%, 69%, 64% and 63% of those in the sham-operated group respectively, and the adenine nucleotide pool contents were 86%, 72%, 68% and 69% of those in the sham-operated group respectively, which were all obviously higher than those in the normothermia control group (P ＜ 0.05). ②Water contents in cerebral cortex: The water content after cerebral ischemia-reperfusion in the normothermia control group was obviously higher than that in the sham-operated group, and gradually aggravated with the prolongation of reperfusion. The water content in the breviscapine group was obviously higher than that in the sham-operated group, but markedly lower than that in the normothermia control group (P ＜ 0.05).CONCLUSION: Breviscapine can play a role in protecting brain through inhibiting disorder of energy metabolism and relieving cerebral edema.

BACKGROUND: Pyramidal cells in hippocampal CA1 region are neurons most susceptible to ischemia-hypoxia damage. Their membrane potential is shown as hyperpolarization of cell membrane during early hypoxia. With the progress of hypoxia time, cell membrane has slow and rapid hyperpolarization, which causes irreversible damage to neurons.OBJECTIVE: To investigate the effects of the blocker of N-methyl-D-aspartate receptor MK801 on the electrophysiological changes of CA1 neurons during hypoxia in isolated hippocampal slices of rats with intracellular recording technique.DESIGN: Observational and controlled study.SETTING: The 97th Hospital of the Chinese PLA, Provincial Key Anesthesiology Laboratory of Xuzhou Medical College; Center of Health Science, State University of New York.MATERIALS: The experiment was conducted from September 2002 to March 2003 in the State University of New York. Five adult male SD rats were anesthetized with 0.02 volume of isoflurane after 3 minutes' pre-oxygenation with oxygen.METHODS: The hippocampal slices from the rats were randomly divided into simple anoxia group (n=10) and MK801 group (n=10). The slices in simple anoxia group were only subjected to 10-minute hypoxia with the artificial cerebrospinal fluid (ACSF), and the slices in MK801 group were treated with 100 μmol/L MK801 for 10 minutes before and during 10 minutes of hypoxia. The neuronal membrane potential before hypoxia, the rate of slow depolarization, the amplitude of and time to rapid depolarization were recorded with intracellular recording technique described in the literature. Meanwhile, the neuronal response to the intracellular current injection and Schaffer collateral stimulation were observed respectively at the end of 60 minutes' re-oxygenation.gion of hippocampal slices: It was significantly higher in simple anoxia group than in MK801 group [(0.20±0.05) mV/s, (0.08±0.03) mV/s, P ＜ 0.05].hippocampal slices: It was significantly higher in MK801 group than in of rapid depolarization of pyramidal cells in CA1 region of hippocampal slices: It was significantly lower in MK801 group than in simple anoxia sponse to stimuli was recovered in 9 out of 10 neurons.CONCLUSION: MK801 blocker of N-methyl-D-aspartate receptor can decrease the rate of slow depolarization of neurons induced by hypoxia, postpone the onset of rapid depolarization of neurons, and decrease the amplitude of rapid depolarization of neurons. This suggests that the blocker of N-methyl-D-aspartate receptor can relieve the hypoxic damage to neurons and promote the functional recovery of neurons.

Objective To investigate the role of gamma-aminobutyric acid transporter-1 (GAT-1) in the spinal cord in a rat model of bone cancer pain.Methods Eighty female SD rats weighing 150-180 g were randomly divided into 5 groups (n =16 each): sham operation group(group Ⅰ ),bone cancer pain group(group Ⅲ ),sham operation+ NO-711 group(group Ⅲ ),Ⅳ group BCP + NO-711 group(group Ⅳ ) and BCP + vehicle group (group Ⅴ ).Bone cancer pain was induced by inoculating Walker-256 mammary gland carcinoma cells into medullary cavity of tibia.NO-711 (20 μg,10 μl) was administered intrathecally once a day for 3 consecutive days from the 14th day after operation.Mechanical withdrawl threshold (MWT) of mechanical stimulus was determined the day before operation and at days 3,5,7,10,14 and 16 after operation.The animals were sacrificed on the 16th day after operation,and then the spinal cords were removed for determination of the expression of GAT-1 and double immunostaining of GAT-1 and glial fibrillary acidic protein (GFAP,astrocyte marker).Results MWT were significantly decreased in groups Ⅱ,Ⅳ and Ⅴ as compared with groups.Ⅰ and Ⅲ.The expression of GAT-1 significantly up-regulated in groups Ⅱ,Ⅴ as compared with groups Ⅰ and Ⅲ.NO-711 significantly increased MWT,while decreased the expression of GAT-1 in group Ⅳ compared with groups Ⅱ and Ⅴ.The expression of GAT-1 up-regulation appeared colocalizes with in astrocytes activation in spinal dorsal horn.Conclusion The up-regulation of expression of GAT-1 in spinal cord is involued in the development and maintenance of bone cancer pain,which may be related to the astrocytes activation.

Aim To investigate the relationship between spinal cord noradrenergic neurons ? 1 adrenoceptors and the spinal analgesia of ketamine. Methods Kunming mice were used. Analgesia tests were investigated with warm water tail flick test. The effects of intrathecal injection (ith) of ketamine (50,100,200 ?g)on tail flick latency of animals were observed. And the effect of pretreatment with intrathecal 6 hydrodoapa(6 OHDA, 6?g ) and ? 1 adrenoceptor antagonist prazosin (5, 15 ?g) or terazosin (5, 15 ?g) , respectively on the spinal analgesia of ketamine (100 ?g,ith) was studied. Results Dose dependent analgesia was observed following ith ketamine (100,200 ?g, P

Objective To investigate the effects of sodium hydroxybutyrate (?-OH) on neuronal apoptosis in neonatal rat cortex induced by hypoxic-ischemic (HI) insult. Methods One-hundred and fifty 7-day old newborn SD rats were randomly assigned to one of S groups ( n = 30 each): sham operation group (A); HI + normal saline (NS) group (B) and three HI + ?-OH groups (C, D, E) . HI was induced by ligation of left common carotid artery followed by 2 h inhalation of hypoxic air (8% O2 92% N2). In sham operation group (A) left common carotid artery was exposed but not ligated and no hypoxic air was inhaled after operation. In group B (HI + NS) NS 0.2 ml?10 g-1 was injected intraperitoneally (IP) t.i.d immediately after HI until the animals were killed; whereas in HI +?-OH groups ?-OH 50 (C) or 100 (D) or 200 (E) mg?kg-1 was injected IP instead of NS. Six animals were killed at 1 h, 3 h, 1 d, 3 d and 7 d in each group and brains were removed. The number of apoptotic neurons in the left cortex was detected using TUNEL staining technique. Results The number of apoptotic neurons at 1 h-7 d after HI was significantly greater in group B, C, D and E than in group A ( sham operation) . The expression of apoptosis positive neurons reached the peak at 1 day after HI. The number of apoptotic neurons at 3 h-3 d was significantly greater in group E (?-OH 200 mg?kg-1) than in group C and D (?-OH 50 and 100 mg?kg-1) . There was no significant difference in the number of apoptotic neurons between group B (HI + NS) and E (HI +?-OH 200 mg?kg-1). Conclusion Sodium hydroxybutyrate 50 and 100 mg?kg-1 can attenuate neuronal apoptosis in neonatal rat cortex induced by hypoxic-ischemic insult.

Objective To investigate the effect of acute injury caused by surgery on spatial learning and memory and the underlying mechanism. Methods Ninty-eight healthy SD rats of both sexes weighing 300-350 g were randomly divided into 3 groups: (A) control group received neither anesthesia nor surgery ( n = 14); (B) anesthesia group received intraperitoneal fentanyl 0.2 mg?kg-1 and droperidol 5 mg?kg-1 only ( n = 42) and ( C) splenectomy group received splenectomy under fentanyl and droperidol anesthesia ( n = 42) . Y-maze test was performed to assess the ability of spatial learning and memory in group A and on the 1 st, 3 rd and 7 th day after anesthesia or surgery in group B and C. Seven rats were killed immediately after Y-maze test in group A and on the 1 st, 3 rd and 7 th day after anesthesia (in group B) and surgery (in group C) , and hippocampus was immediately removed for determination of the expression of TNF-? and IL-1? mRNA (RT-PCR) and protein (Western blot). Results The voltage of electric stimulation was significantly higher in group C on the 1st day after surgery than in group B on the 1st day after anesthesia and in group A. The time spent to learn and remember in Y-maze test was significantly longer in group C on the 3 rd than in group B on the 3 rd day and in group A. The expression of TNF-? mRNA and IL-1? mRNA and protein was significantly higher in group C than in group B on the 1st day and in group A.Conclusion Splenectomy can impair the spatial learning ability for a short time after surgery. The increase in the expression of TNF-? mRNA and IL-1? mRNA and protein in hippocampus may play a role in the mechanism.

Objective To investigate the relationship between N-methyl-D aspartate (NMDA) receptors and the hypnotic and analgesic effects of enflurane, isoflurane and sevoflurane. Methods Kunming mice weighing 18-22 g were used in this study. The experiment was carried out in 2 parts. In Part I 120 mice were randomly divided into 3 groups (n =40 each); each group received intraperitoneal (IP) enflurane 2 ml?kg-1 or isoflurane 1.2 ml?kg-1 or sevoflurane 5 ml?kg-1 . Each group was further divided randomly into 4 subgroups ( n = 10 each) and each subgroup received artificial cerebro-spinal fluid (aCSF) 10 ?l or NMDA 25, 50 or 75 ng in 10 ?l aCSF injected into the lateral ventricle of the brain as soon as the animals lost righting reflex. The time for the recovery of righting reflex was recorded. In Part Ⅱ 160 mice were randomly divided into 4 groups ( n = 40 each) : ( 1) control group received no inhalation anesthetic; (2) enflurane group received enflurane 1.5 ml?kg-1 subcutaneously s.c. ; (3) isoflurane group isoflurane 0.8 ml?kg-1 s.c. and (4) sevoflurane group sevoflurane 4.5 ml ?kg-1 s.c. Each group was further divided randomly into 4 subgroups ( n = 10 each). Each subgroup received intrathecal (IT) aCSF 10 ?l or NMDA 2.5 ng or 5.0 ng or 10 ng in aCSF 10 ?l at 10 min after subcutaneous injection of inhalation anesthetic. 6% acetic acid 0.1 ml?10 g-1 was injected IP at 1 min after intrathecal administration. The number of writhing induced by acetic acid was recorded. Results In Part Ⅰ of the experiment there was no significant difference in the duration of anesthesia induced by the 3 inhalation anesthetics between the 4 subgroups. In Part Ⅱ subcutaneous injection of the 3 inhalation anesthetics significantly reduced the number of writhing induced by IP acetic acid. In control group which received no inhalation anesthetic there was no significant difference in the number of writhing between the 4 subgroups. In the 3 inhalation anesthetic groups NMDA5. 0 and 10 ng IT significantly increased the number of writhing induced by IP acetic acid in a dose dependent manner as compared with aCSF subgroup. Conclusion Cerebral NMDA receptors do not play an important role in the hypnotic effect of enflurane, isoflurane and sevoflurane while spinal NMDA receptors are involved in the analgesic effect of the 3 inhalation anesthetics.

Aim To explore the effect of propofol preconditioning on cardiocyte apoptosis and cytochrome C release from mitochondria during hypoxia/reoxygenation in isolated rat hearts.Methods Fifty male Sprague-Dawley rats weighing 250～300 g were randomly divided into 5 groups(n=10 each):control group(C);Dimethyl sulfoxide(DMSO)preconditioning group(D);3 propofol preconditioning groups with 25 ?mol?L-1(P1)、50 ?mol?L-1(P2)、100 ?mol?L-1(P3)propofol respectively.The isolated rat hearts were retrogradely perfused via aorta with K-H solution on Langendorff apparatus.The isolated hearts were made hypoxia for 30 minutes followed by 60 minutes reoxygenation in each group.The D,P1,P2,P3 groups were preconditioned by perfusing 10 min K-H solution containing 20 ?mol?L-1 DMSO and 25,50,100 ?mol?L-1 propofol respectively and then followed by 5 min K-H solution reperfusion before hypoxia.The preconditioning procedure was repeated twice.The cardiac functional variables were recorded after equilibration(baseline values),immediately before hypoxia,at the end of 30 min and 60 min reoxygenation.Apoptotic myocardial cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling(TUNEL)and the level of cytochrome C expression in myocardial cytosol and mitochondria was measured by Western blot at the end of reoxygenation.Results At the end of 30 min and 60 min reoxygenation,LVEDP was significantly lower and LVDP was significantly higher in P1,P2,P3 groups than in D group(P