Yu-hua Ran1, Hai Wang. 1. Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing, China.
Abstract
OBJECTIVE: To investigate the role of iptakalim, an ATP-sensitive potassium channel opener, in transient cerebral ischemia/reperfusion (I/R) injury and its involved mechanisms. METHODS: Intraluminal occlusion of middle cerebral artery (MCAO) in a rat model was used to investigate the effect of iptakalim at different time points. Infarct volume was measured by staining with 2,3,5-triphenyltetrazolium chloride, and immunohistochemistry was used to evaluate the expressions of Bcl-2 and Bax. In vitro, neurovascular unit (NVU) cells, including rat primary cortical neurons, astrocytes, and cerebral microvascular endothelial cells, were cultured and underwent oxygen-glucose deprivation (OGD). The protective effect of iptakalim on NVU cells was investigated by cell viability and injury assessments, which were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and release of lactate dehydrogenase. Caspase-3, Bcl-2 and Bax mRNA expressions were evaluated by real-time polymerase chain reaction (PCR). RESULTS: Administration of iptakalim 0 or 1 h after reperfusion significantly reduced infarct volumes, improved neurological scores, and attenuated brain edema after cerebral I/R injury. Iptakalim treatment (0 h after reperfusion) also reduced caspase-3 expression and increased the ratio of Bcl-2 to Bax by immunohistochemistry. Iptakalim inhibited OGD-induced cell death in cultured neurons and astrocytes, and lactate dehydrogenase release from cerebral microvascular endothelial cells. Iptakalim reduced mRNA expression of caspase-3 and increased the ratio of Bcl-2 to Bax in NVU cells. CONCLUSIONS: Iptakalim confers neuroprotection against cerebral I/R injury by protecting NVU cells via inhibiting of apoptosis.
OBJECTIVE: To investigate the role of iptakalim, an ATP-sensitive potassium channel opener, in transient cerebral ischemia/reperfusion (I/R) injury and its involved mechanisms. METHODS:Intraluminal occlusion of middle cerebral artery (MCAO) in a rat model was used to investigate the effect of iptakalim at different time points. Infarct volume was measured by staining with 2,3,5-triphenyltetrazolium chloride, and immunohistochemistry was used to evaluate the expressions of Bcl-2 and Bax. In vitro, neurovascular unit (NVU) cells, including rat primary cortical neurons, astrocytes, and cerebral microvascular endothelial cells, were cultured and underwent oxygen-glucose deprivation (OGD). The protective effect of iptakalim on NVU cells was investigated by cell viability and injury assessments, which were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and release of lactate dehydrogenase. Caspase-3, Bcl-2 and Bax mRNA expressions were evaluated by real-time polymerase chain reaction (PCR). RESULTS: Administration of iptakalim 0 or 1 h after reperfusion significantly reduced infarct volumes, improved neurological scores, and attenuated brain edema after cerebral I/R injury. Iptakalim treatment (0 h after reperfusion) also reduced caspase-3 expression and increased the ratio of Bcl-2 to Bax by immunohistochemistry. Iptakalim inhibited OGD-induced cell death in cultured neurons and astrocytes, and lactate dehydrogenase release from cerebral microvascular endothelial cells. Iptakalim reduced mRNA expression of caspase-3 and increased the ratio of Bcl-2 to Bax in NVU cells. CONCLUSIONS:Iptakalim confers neuroprotection against cerebral I/R injury by protecting NVU cells via inhibiting of apoptosis.
Authors: Daisuke Tsuchiya; Shwuhuey Hong; Yasuhiko Matsumori; Hiroaki Shiina; Takamasa Kayama; Raymond A Swanson; Wolfgang H Dillman; Jialing Liu; S Scott Panter; Philip R Weinstein Journal: J Cereb Blood Flow Metab Date: 2003-06 Impact factor: 6.200
Authors: B Kis; H Kaiya; R Nishi; M A Deli; C S Abrahám; T Yanagita; T Isse; S Gotoh; H Kobayashi; A Wada; M Niwa; K Kangawa; J Greenwood; H Yamashita; Y Ueta Journal: J Neuroendocrinol Date: 2002-04 Impact factor: 3.627