| Cerebrovascular diseases are the third cause for death in the whole world, among which about 2/3 patients are suffered from cerebral ischemia/reperfusion(I/R) injury. Therefore the study in this field has been an important aspect of medical research. With the progress of study on pathophysiology of I/R injury, some clinical therapies have proved successful to a certain extent. But the drug therapies can not solve the problem completely. It has been proved that both Shenfu Solution and isoflurane preconditioning could induce neuroprotective effects against I/R injury in the brain. However, more studies are needed to clarify the protective effects and mechanisms. The present study was designed to evaluate the following objectives in a rat MCAO model. (l) To investigate the therapeutic time window for Shenfu solution in transient focal cerebral ischemic injury; (2) To investigate the synergistic neuroprotective effects of combining isoflurane preconditioning with Shenfu solution; (3) To determine if repeated brief isoflurane anesthesia induces ischemic tolerance to focal cerebral ischemia dependent on KATP channels; ?To investigate if brief-4-isoflurane anesthesia induces neuroprotective effect against transient focal cerebral ischemia. Experiment 1:Objective: To investigate the therapeutic time window for Shenfu solution in transient focal cerebral ischemic injury. Methods: Eighty male SD rats weighing 280~350g were randomized into eight groups(n=10 in each group): Control group, received no pharmacological intervention, Groups A-G, received intraperitoneal injection of Shenfu solution (10ml fcg"1) at 0, 30, 60, 90, 120, 240 and 360min respectively after 120min middle cerebral artery occlusion (MCAO) with 3-0 nylon monofilament via the right internal carotid artery. The neurologic outcome was evaluated at 24h after reperfusion. The brain infarct volume was then determined by TTC staining. Results: The neurologic deficit scores (NDS) in animals of A-F groups at 24h after reperfusion were obviously lower than those of Control and G groups^O.OS). The infarct volumes of Control G groups were significantly larger than those of Groups A-F (P<0.05) at 24h after reperfusion. There were no differences among groups A-F for both NDS and infarct volume. Conclusion: Therapeutic time window for Shenfu solution in transient focal cerebral ischemic injury lasts for at least 4h . Experiment 2:Objective: To investigate the synergistic neuroprotective effects of combining isoflurane preconditioning with Shenfu solution in rats subjected to reversible focal cerebral ischemia. Methods: Forty male SD rats (weighing 300~350g) were randomly divided into four groups(n=10 in each group). Animals in Control group received no pharmacological intervention, animals in Shen group received intraperitoneal injection of Shenfu solution(10ml ?kg"1) at30 minutes before ischemia, animals in Iso group received 1 hour of 2%-5-isoflurane in 98% oxygen every day for five days, animals in Iso-Shen group received both treatments same with that in groups Shen and Iso. The rat MCAO model and measurements were the same as those in Experiment 1. Results: The neurologic deficit scores (NDS) in groups Shen, Iso and Iso-Shen at 24 hours after reperfusion were obviously lower than that of Control group (PO.05). There were no differences among the three treated groups. The infarct volume of Control group was significantly larger than that of groups Shen, Iso and Iso-Shen (P<0.05) at 24 hours after reperfusion. And the infarct volume of group Iso-Shen was obviously smaller than that of groups Shen and Iso(/5<0.05). There was no difference between groups Shen and Iso. Conclusion: By combining isoflurane preconditioning with Shenfu solution in rats subjected to reversible focal cerebral ischemia, synergistic neuroprotective effects could be induced to a certain extent. Experiment 3:Objective: This study was to determine if repeated brief isoflurane anesthesia induces ischemic tolerance to focal cerebral ischemia dependent on KATP channe... |
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