Chloride Co-transporter NKCC1 Inhibitor Bumetanide Enhances Neurogenesis and Behavioral Recovery in Rats After Experimental Stroke |
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Authors: | Wangshu Xu Xiaopeng Mu Huibin Wang Chengguang Song Wenping Ma Jukka Jolkkonen Chuansheng Zhao |
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Institution: | 1.Department of Neurology, The First Affiliated Hospital,China Medical University,Shenyang,People’s Republic of China;2.Department of Neurology, Beijing Tiantan Hospital,Capital Medical University,Beijing,People’s Republic of China;3.Department of Neurology,Benxi Central Hospital of China Medical University,Benxi,People’s Republic of China;4.Department of Medical Genetics, School of Basic Medicine,Peking University,Beijing,China;5.Institute of Clinical Medicine – Neurology,University of Eastern Finland,Kuopio,Finland |
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Abstract: | Bumetanide, a selective Na+-K+-Cl?-co-transporter inhibitor, is widely used in clinical practice as a loop diuretic. In addition, bumetanide has been reported to attenuate ischemia-induced cerebral edema and reduce neuronal injury. This study examined whether bumetanide could influence neurogenesis and behavioral recovery in rats after experimentally induced stroke. Adult male Wistar rats were randomly assigned to four groups: sham, sham treated with bumetanide, ischemia, and ischemia treated with bumetanide. Focal cerebral ischemia was induced by injection of endothelin-1. Bumetanide (0.2 mg/kg/day) was infused into the lateral ventricle with drug administration being initiated 1 week after ischemia and continued for 3 weeks. Behavioral impairment and recovery were evaluated by tapered/ledged beam-walking test on post-stroke days 28. Then, the rats were perfused for BrdU/DCX (neuroblast marker), BrdU/NeuN (neuronal marker), BrdU/GFAP (astrocyte marker), and BrdU/Iba-1 (microglia marker) immunohistochemistry. The numbers of neuroblasts in the subventricular zone (SVZ) were significantly increased after the experimentally induced stroke. Bumetanide treatment increased migration of neuroblasts in the SVZ towards the infarct area, enhanced long-term survival of newborn neurons, and improved sensorimotor recovery, but it did not exert any effects on inflammation. In conclusion, our results demonstrated that chronic bumetanide treatment enhances neurogenesis and behavioral recovery after experimentally induced stroke in rats. |
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