| Stroke is the third-leading cause of death in western countries such as the United States and Canada. About 24ï¼…strokes are fatal and 50ï¼…of survivors will have a mild disability. It estimates that Americans will pay about $62.7 billion in 2007 for stroke-related medical costs and disability. Stroke can really put a burden on our society and government. There are two major types of stroke: Occlusive stroke which accounts for nearly 80ï¼…of all strokes and hemorrhagic stroke which accounts for about 20ï¼…of strokes. Stroke patients can have a surgery to recover the blood flow or can be treated with some effective medines including thrombolytics and some neuroprotective agents. However, these methods are not satisfactory. Our ability to treat stroke is very limited eventhough our knowledge of the stroke is growing very fast. Now it is ergent to find some new and effective agents to treat strokes.As a well-known Chinese Traditional Medicne, Angelica sinensis(Oliv.) Diels (ASD), named Danggui in China, has mutilple roles in pharmacological and biological areas. The major components of ASD are water-soluble substances and volatile oil. While the former including ferulic acid and polysaccharides are widely used in clinic, the effective substance basis of the essential oil is not completely clear. Our previous studies showed that LIG significantly prevented transient ischemic brain damage. The oral administration of LIG (20, or 80 mg/kg), at 0 and 4 h again after reperfusion following 2 h ischemia, significantly reduced infarct volumes and improved neurological scores in transient middle cerebral artery (MCA) occlusion model of rats. In addition, LIG (5, or 20 mg/kg, i.p.) could also remarkably reduce the infarct volume in the transient forebrain ischemic mice in a dose-dependent manner. It is reported that the cerebral ischemia due to lasting vascular blockage plays more important role in clinical ischemic stroke. In order to further investigate the protection of LIG on focal brain ischemia, the present study therefore evaluated its effect and therapeutic time window in rat permanent MCA occlusion model. The effect of LIG on infarct volumes, CBF, edema, neurological scores and body temperature was assessed in this study.In the first part of our experiment, focal cerebral ischemia was induced by the occlusion of middle cerebral artery (MCA) for 24 h.. Rats were divided randomly into Control, low dose and high dose groups. LIG (20, or 80 mg/Kg) or the same volume of 3ï¼…tween 80, were orally administered at 2 h after ischemia. The neurological function of rats were evaluated at 24h after surgery. Brain ischemic volumes were measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Brain swelling were calculated by Image Analysis software. Rectal body temperature were also monitored before and 2,3,4,6,7,24 hours after MCAO. In the part, our data indicated that Z-Ligustilide can improve the neurological scores of MCAO rats significantly as well as the brain edema and infarct volume. Therefore, it concluded that Z-Ligustilide can have protective effect in MCAO rats.In the seconde part of our experiment, we tried to elucidate the effective therapeutic time window of Z-Ligustilide in PMCAO model of rats. We administered Z-Ligustilide at dosages of 20mg/kg, 10mg/kg, 5mg/kg 15min before surgery and found Z-Ligustilide can significantly decrease the infarct volume of MCAO rats and improve the their neurologcial scores but had no effect on CBF of rats. Further study showed that Z-Ligustilide showed neuroprotective effects even administered 6h after MCAO surgery. |
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