Abstract
In our recent study, BMS-191095, a newly developed selective mitoKATP channel opener induced preconditioning in primary cultures of rat cortical neurons (B. Kis et al. NeuroReport 15:345–349, 2004). However whether BMS-191095 protects the brain against ischemic stress has not been studied. We investigated the effect of BMS-191095 against 90 min transient middle cerebral artery occlusion (MCAO) in male Wistar rats. BMS-191095 was infused into the left lateral ventricle 30 min (0.4 mM, n=11, or 4 mM, n=6), 60 min (4 mM, n=7) and 24 hr (4 mM, n=12, in 15 μL dimethyl sulfoxide) before MCAO. Infarct volumes were measured 72 hr after reperfusion. Treatment with BMS-191095 24 hr before MCAO but not 30–60 min exhibited a 29% reduction (206.2 ± 16.5 vs 149.2 ± 18.2 mm3) and a 34% reduction (144.2 ± 15.4 vs 95.2 ± 14.4 mm3) in infarct volumes for total brain and cortex, respectively. The protective effect of BMS-191095 was completely prevented by the pretreatment with 5-hydroxydecanoate (5-HD), a selective blocker of mitoKATP channels (40mg/kg IP; n=8). Intraventricular administration of BMS-191095 did not changed local cerebral blood flow measured with laser-Doppler flowmetry. BMS-191095 depolarized the mitochondrial membrane potential without increasing the ROS production in cultured rat cortical neurons, which was dose dependently inhibited by 5-HD. These results suggest that opening of mitoKATP channels exhibits delayed preconditioning in the rat brain and this effect is dissociated from ROS production. Supported by NIH grants (HL-30260, HL-46558, HL-50587, DK-62372) for D. W. Busija.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
