| Cerebrovascular diseases (CVD) have endangering human's health seriously for the high incidence, disability and death rates, and ischemic cerebrovascular diseases (ICVD) make up most part of the incidence rate of CVD. The mechanisms of the cerebral ischemia and reperfusion injury are not definite, usually we thougut it including a series of pathophysiological procedure such as excitatory amino acid (EAA) neurotoxicity, calcium overload, inflammation, free radical and apoptosis etc. Thus, a reasonable strategy to treat ischemic stroke should include the following two approaches, one is to restore cerebral blood flow (CBF), the other is to block the damdging cascade of biochemical events initiated by the reduction of CBF. Thromlysis is the basic way to recanalize blood vessels and urokinase (UK) is one of the most usual thrombolytic drug in our nation. Unfortunately, the serious risk ofcerebral hemorrhage and the very short therapeutic window of 6 even 3 hours postischemia are the important limitation to the widespread use of UK in the management of acute stroke. It is possible that the addition of neuropective therapies may augment the efficacy of thrombolysis and enlarge the therapeutic window by blocking the ischemic neuronal injury. As the physiological antagonist of calcium and uncompetitive N-methyl-D-aspartate receptor blocker, magnesium can decrease pathological calcium influx, relieve the neurotoxicity of EAA, scanvenge oxygen free radical in blood, and has been proved to produce significant neuroprotection on cerebral ischemia. Ultraviolet liquid irradivation (ULI) can improve the activities of tissue plasminogen activator (tPA), decrease the level of fibrinogen in plasma and relieve free radical's injury. This experiment is to study the effect of combining urokinase and magnesium or ULI on focal cerebral ischemia, via observing the changes of neurological function, infarct size, pathology of cerebral tissue, and examing the content of endothelin (ET) and nitric oxide (NO), provide an experimental theory for the use of combining therapy with thrombolysis and neuroprotective agent for ICVD. Materials and MethodsNinety-six healthy Wistar rats weighting from 220 to 250 grams were randomly assigned to the following five groups: Group A, sham-operated group, animals were only irradiated by He-Nelaser after exposing the left middle cerebral artery (six rats); Group B, animals in the saline-treated group that received 3ml saline infusions via the femoral vein at 2, 6 and 10 hours postsurgery (each has six rats); Group C, thrombolysis groups that received urokinase (60000U/Kg) at 2, 6 and 10 hours after ischemic insult (eight rats in each group); Group D, animals in the combination groups that received urokinase (60000U/Kg) and magnesium sulfate (500mg/Kg) at 2, 6 and 10 hours after ischemic insult (eight rats in each group); Group E, animals received urokinase (60000U/Kg) which had been irradiated by ultraviolet for 8~10 minutes at 2, 6 and 10 hours postischemia (eight rats in each group). Urokinase were dissolved with 3ml saline and then administered via the femoral vein, magnesium sulfate was given intraperitoneally immediately after the infusion of urokinase. Middle cerebral artery occlusion model in rats was induced by photochemistry and signs were observed after rats having awaken from anesthesia. The evaluation of neurological deficit was conducted at 24 hours after MCAO and the neurological findings were scored on a five-point grade scale reported by Bederson, after that, blood was abtained to determin the content of endothelin and nitric oxide. At last, rats were killed and brains were removed from the skull, l~2mm thick coronal sections were cut and stained using TTC to observe the location and region of infarct volume. Other 26 healty Wistar rats were divided into five groups the sameas the above, the brain tissue 5~7mm away from forehead was cutfor 5 u m sections 24h postischemia and stained with hemotoxylin-eosin (H.E) to examine the histological changes of brain tissueunder... |
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