TY - JOUR AU - WONG Raymond AU - ABUSSAUD Ahmed AU - WH LEUNG Joseph AU - XU Bao-feng AU - LI Fei-ya AU - HUANG Sammen AU - CHEN Nai-hong AU - WANG Guan-lei AU - FENG Zhong-ping AU - SUN Hong-shuo PY - 2018 TI - Blockade of the swelling-induced chloride current attenuates the mouse neonatal hypoxic-ischemic brain injury in vivo JF - Acta Pharmacologica Sinica; Vol 39, No 5 (May 2018): Acta Pharmacologica Sinica (Special Issue on Frontier in Medical Research and Drug Development) Y2 - 2018 KW - N2 - Abstract Activation of swelling-induced Cl – current ( I Cl,swell ) during neonatal hypoxia-ischemia (HI) may induce brain damage. Hypoxic-ischemic brain injury causes chronic neurological morbidity in neonates as well as acute mortality. In this study, we investigated the role of I Cl,swell in hypoxic-ischemic brain injury using a selective blocker, 4-(2-butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl) oxybutyric acid (DCPIB). In primary cultured cortical neurons perfusion of a 30% hypotonic solution activated I Cl,swell , which was completely blocked by the application of DCPIB (10 μmol/L). The role of I Cl,swell in neonatal hypoxic-ischemic brain injury in vivo was evaluated in a modified neonatal hypoxic-ischemic brain injury model. Before receiving the ischemic insult, the mouse pups were injected with DCPIB (10 mg/ kg, ip). We found that pretreatment with DCPIB significantly reduced the brain damage assessed using TTC staining, Nissl staining and whole brain imaging, and improved the sensorimotor and vestibular recovery outcomes evaluated in neurobehavioural tests (i.e. geotaxis reflex, and cliff avoidance reflex). These results show that DCPIB has neuroprotective effects on neonatal hypoxic-ischemic brain injury, and that the I Cl,swell may serve as a therapeutic target for treatment of hypoxic-ischemic encephalopathy. UR - http://www.chinaphar.com/article/view/9784