Iptakalim, an ATP-sensitive potassium channel opener, confers neuroprotection against cerebral ischemia/reperfusion injury in rats by protecting neurovascular unit cells

• Published in: Journal of Zhejiang University. B. Science Vol. 12; no. 10; pp. 835 - 845
• Main Authors: Ran, Yu-hua, Wang, Hai
• Format: Journal Article
• Language: English
• Published: Heidelberg SP Zhejiang University Press 01.10.2011; Springer Nature B.V; Zhejiang University Press
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Brain Edema - drug therapy; Cerebral Infarction - drug therapy; KATP Channels - drug effects; L-Lactate Dehydrogenase - secretion; Male; Neuroprotective Agents - therapeutic use; Propylamines - therapeutic use; Rats; Rats, Sprague-Dawley; Reperfusion Injury - prevention & control; Cerebral ischemia/reperfusion (I/R) injury; Neuroprotection; Neurovascular unit; ATP-sensitive potassium channel opener; R96; Apoptosis
• ISSN: 1673-1581; 1862-1783
• DOI: 10.1631/jzus.B1100067

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.