title: Chloride Co-transporter NKCC1 Inhibitor Bumetanide Enhances Neurogenesis and Behavioral Recovery in Rats After Experimental Stroke.
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.
authors.affiliation: Department of Neurology, The First Affiliated Hospital, China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, People's Republic of China.|Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, 6 Tian Tan Xi Li, Beijing, People's Republic of China.
authors.forename: Wangshu
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Neurology, The First Affiliated Hospital, China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, People's Republic of China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Mu
authors.affiliation: Department of Neurology, The First Affiliated Hospital, China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, People's Republic of China.
authors.forename: Huibin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurology, Benxi Central Hospital of China Medical University, NO.29 Shengli Road, Mingshan Ward, Benxi, Liaoning, People's Republic of China.
authors.forename: Chengguang
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Medical Genetics, School of Basic Medicine, Peking University, Xueyuan Road, Haidian District, Beijing, 100191, China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Ma
authors.affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland, P. O. Box 1627, 70211, Kuopio, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Jolkkonen
authors.affiliation: Department of Neurology, The First Affiliated Hospital, China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning, People's Republic of China. cszhao@mail.cmu.edu.cn.
authors.forename: Chuansheng
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D020520:Brain Infarction / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002034:Bumetanide / Q000494:pharmacology* / Q000627:therapeutic use*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D017208:Rats, Wistar; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism*; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D034961:Antigens, Nuclear; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C546339:Rbfox3 protein, rat; D064506:Solute Carrier Family 12, Member 2; D002034:Bumetanide; D001973:Bromodeoxyuridine
keywords: Behavioral recovery; NKCC1 inhibitor; Neurogenesis; Neuronal survival; Stroke