| Summary: | 碩士 === 中國醫藥大學 === 免疫學研究所碩士班 === 102 === Traumatic brain injuries (TBIs) are a major health care problem worldwide. TBI is a risk factor for developing neurodegenerative diseases and associated with long-term cognitive and behavioral dysfunction. Approximate 1.7 million people undergo TBI annually in the United States, of whom 275,000 are admitted to hospitals and 52,000 suffer TBI-related deaths. Of the 275,000 people who are hospitalized with TBI each year, approximately 5–7% experience a posttraumatic seizure (PTS). Study found that excessive extracellular glutamate after traumatic brain injury (TBI) contributes to excitotoxic cell death and likely to posttraumatic epilepsy. Therefore, to avoid the generation of epilepsy after TBI is one of important research direction. Valproic acid (VPA) , a histone deacetylase inhibitor (HDACi) , is mainly used as an anticonvulsant and mood-stabilizing drugs. Recently, VPA has been shown its antiinflammatory and anti-apoptotic properties in many neuronal injuries. The purpose of dissertation is to use the rat model of traumatic brain injury, and post-traumatic with VPA treatment, and assess the impact of traumatic brain injury treatment with VPA.
In this study, after using a controlled cortical impact device for establishing TBI model in rats, TBI rats were then treated with or without various concentration of VPA and were analyzed behaviors of motor coordination through a rotarod test analyzer. After 7 days, TBI rats treated with or without VPA were scarified and collected brain tissue for detection of different protein productions. Sprague–Dawley (SD) rats (male, 6-8 weeks) were randomized into three groups: sham, TBI treated with or without VPA. In this study, we had found that the bleeding region in the brain was decreased after TBI rats treated with VPA for 7 days. It had also been shown the significant decreasing of positive GFAP staining in brain tissues obtained from TBI rats treated with VPA. Meanwhile, TBI rats treated with VPA had significantly improved the motor coordination by the Rotarod analysis. Western blot analysis demonstrated that significantly decreasing production of caspase-3, GFAP and p-Erk expression following VPA treatment at the 7-days of post-TBI in the brain. Through this study found that VPA effectively reduced caspase-3, GFAP and p-Erk expression and promoted accelerate movement to resilience in rats. Administration of VPA had been increased production of p-β-catenin. Here, we might provide the molecular insight to protective mechanism of VPA after brain injury.
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