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Lysophosphatidic acid receptors mediate the reduction of rat brain infarct volume

Abstract
Stroke is a potentially lethal cerebrovascular event. Many research studies devoted to the treatment of stroke. In a recent study, sphingosine-1-phosphate (S1P) has the function of reducing the brain infarct volume. However, no study has yet demonstrated that lysophosphatidic acid (LPA) has this function. LPA and S1P are thought to be the two functionally important LPLs with high structural similarity. Although the neuroprotective function of S1P in TIA rat was confirmed, the effects of LPA on the brain damage after ischemic stroke of animal remain unclear.
In this study we evaluated the neuroprotective effects of LPA1/3 receptor agonist (VPC31143; VPC) on rat brains subjecting to permanent middle cerebral artery occlusion (PMCAO). A reliable surgical model of rat PMCAO was first established. Thereafter, the animals were divided into control, vehicle, high-dose VPC, and low-dose VPC groups. The vehicle group received intraperitoneal (i.p.) injection of 3% bovine serum albumin (BSA; 1 ml/kg) 30 minutes after PMCAO surgery. The high-dose VPC and the low-dose VPC group respectively received 0.8 mg/kg and 0.25 mg/kg of i.p. injection of VPC (in 3% BSA) 30 minutes after PMCAO surgery. The mortality rate, infarct volume ratio, and the neurobehavioral outcome were measured 24 hours after PMCAO and statistically analyzed for the difference between treatments.
Analyses of the experimental results showed that VPC treatment significantly reduced the mortality rate and the infarct volume ratio of the rats 24 hours after PMCAO. The neurobehavioral scores also showed the improved outcome in stroke rats treated with VPC. The beneficial effect of VPC to the ischemic brain was thought to be mediated through the PI3K signal transduction pathway. Further studies at the transcriptional and the translational levels will further confirm this postulation.

Identiferoai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0721111-185333
Date21 July 2011
CreatorsTsai, Ping-Ju
ContributorsMing-Hong Tai, Hay-Yan J. Wang, Chao-Neng Tseng
PublisherNSYSU
Source SetsNSYSU Electronic Thesis and Dissertation Archive
LanguageCholon
Detected LanguageEnglish
Typetext
Formatapplication/pdf
Sourcehttp://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0721111-185333
Rightsnot_available, Copyright information available at source archive

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