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Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke. The narrow treatment time window is still to be solved. Given that the ischemic core expanded over days, treatment with an extended time window is anticipated. Bestrophin 1 (BEST1) belongs to a bestrophin family of calcium-activated chloride channels. We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice. Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits. Using electrophysiological recordings, we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity. Finally, we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6-72 h post-ischemia in rodents. This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions. Our study identifies the glutamate-releasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.
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OBJECTIVE: To study the development strategy of clinical pharmacy under the condition of New Medical Reform in China. METHODS: The status quo and obstacle factors of clinical pharmacy were analyzed to probe into the chance for clinical pharmacy in China brought out by New Medical Reform. RESULTS: The reimbursement mechanism reform of state hospitals, National Essential Drug System, medical insurance system, charge for pharmaceutical care system and the construction of primary hospitals and public health service provide development opportunities of clinical pharmacy. CONCLUSION: The development strategy of clinical pharmacy should be associated with New Medical Reform and relevant policy, laws and regulations of clinical pharmacy should be improved. Great importance should be attached to exploring the training system of clinical pharmacists and approaches of clinical pharmacy.
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Aim To explore the effect of nNOS specific inhibitor 7-nitrioindazole(7-NI) on the neurogenesis after focal cerebral ischemia in the adult mice dentate gyrus.Methods Focal cerebral ischemia was induced by middle cerebral artery occlusion(MCAO).A bromodeoxyuridine(BrdU) method was used to identify the proliferated cells in hippocampal dentate gyrus.Step-down test was performed to assay the learning and memory function.Results The number of BrdU~+ cells was increased in the ipsilateral but not contralateral dentate gyrus after focal cerebral ischemia.7-NI promoted the increment in the ipsilateral dentate gyrus significantly.7-NI also improved the survival of the new-born cells,as well as the learning and memory function of ischemic mice.Conclusion Our results indicate that nNOS down-regulates the neurogenesis after focal cerebral ischemia.
