Study of neuroprotective effect of diazoxide on different brain regions of neonatal rats with hypoxic-ischemic encephalopathy
LIN Ni-yang
FANG Xiao-yi
CHEN Yu-xia
Abstract:Objective To investigate the protective effects of diazoxide,a KATP channel opener,on different brain regions of neonatal rats with hypoxic-ischemic brain damage (HIBD) induced by intrauterine asphyxia.Methods The intrauterine asphyxia model was performed by clamping the uterine veins and arteries of the pregnant rats at the 21st day of gestation and the pups were bom by cesarean section.They were randomly divided into four groups:hypoxia-ischemia (HI) group,diazoxide (Dia) group,diazoxide + glibenclamide (Dia + Gli) group and solvent (NaOH) group.The neonatal rats in control group were born after the uterine vessels of the pregnant rats were isolated but not clamped.No drugs were used in HI and control group; otherwise,the intervention medicine was injected intraperitoneally at 0 h,12 h and 24 h after birth in other three groups.The neonatal rats were sacrificed 72 h after birth.The cerebral infarction areas were measured by TTC staining,the histopathologic scores were calculated after HE staining in cortex,hippocampus,cerebellum,thalamus and brainstem and the mRNA of the subunits of the KATP channel were detected by RT-PCR in different brain regions.Results The differences of the cerebral infarction areas between the HI group and control group,Dia group and HI group and Dia + Gli group and Dia group were significant (P <0.05).The infarction areas in HI group were high and those were decreased after the treatment of Diazoxide.The histopathologic scores were significantly different among the five brain regions in HI group (P < 0.05):hippocampus (4.60 ± 0.52) and cortex (4.50 ± 0.53) were the most serious injured regions,the next was cerebellum (4.20 ± 0.63).In hippocampus and cortex,the light density of Kir6.2 mRNA in Dia group(2.56 ± 0.88 and 2.48 ± 0.41) had no significant difference compared with that in control group(3.27 ± 0.38 and 3.06 ± 0.81).Conclusions Hippocampus and cortex are the most seriously injured regions after HIBD induced by intrauterine asphyxia in neonatal rats.Diazoxide,a KATP channel opener,has neuroprotective effect on the five brain regions,especially on the hippocampus and cortex.
Keywords:ATP-sensitive K+ channelDiazoxideHypoxia-ischemic brain injuryNewborn rats
Publication Date:2013-01-01
Online Publishing Date:2026-09-14(First online date of this platform, not the publication date of the document)
Pages:4( 1095-1098 )
