| Objective: Ischemia,with high mortality and serious disability,is the most common type of cerebral vascular disease. Thrombolytic treatment in early stage has proved to be one of the effective therapies in acute cerebral infarction (CI). However, the risk of hemorrhagic transformation (HT) often limits its use in clinical practice and HT after CI develops a special type of ischemia. It have been reported that adenosine triphosphate sensitive potassium channels (KATP channels),focused on cerebral ischemia research recently,would open in early stage of ischemia,which was an important self-protection.The invasion of the blood complicates the pathologic process of HT,so the histology changes and mechanism of brain injury were not clear.Whether KATP channels participate in HT or whether HT would aggrevate the ischemic brain injury was unknown.A ideal animal model is important for disease research,but until recently, there has been no reproducible and reliable HT model developed.The study is to establish CI model and combined the intercerebral hemorrhage(ICH) model technique to develop a stable HT model in rats,which present the effect of blood on the ischemia.Then study would carried out on pathology changes of HT and comparisons with pure CI in neurobehavioral deficit,brain edema and brain adenosine triphosphatase (ATPase) activity, succinic dehydrogenase (SDH) activity and malondialdehyde (MDA) content. At the same time, Glibenclaimide (Gli),an KATP channels blocker,was used in HT to look for whether KATP channels participated in HT.Methods:Male,healthy Sprague-Dawley rats were used and randomly assigned to four groups, hemorrhagic transformation (HT), cerebral infarction (CI), Gli + HT (GH) and Sham group. Intraluminal thread technique was used to create the CI model.Two steps were used to combine the CI and ICH model technique to develop the HT model in rats.First, right middle cerebral artery was occluded using the intraluminal thread technique.Second,50μl arterial blood was injected into the caudate nucleus where the infarction happened.Neuronal behavior was evaluated with Longa test, Berderson test and Beam test at 3rd, 6th, 12th and 24th hours after operation.And then rats were sacrificed for brain water content,brain ATPase activity,SDH activity and MDA content measurement. Triphenyltetrazolium chloride (TTC) staining was used to observe the HT after CI in fresh brain samples. Histology in HT was examined with light microscope and transmission electron microscope.Results:1 The neurobehavioral deficit were tested by Longa test, Berderson test and Beam test.Rats in HT group,CI group performed a right palsy and a left Horner sign, while in Sham group did none.Scores comparisons showed that there was no significant difference between HT group and CI group (P>0.05), but both of them were higher than Sham group (P<0.05).2 Brain water content of both HT group and CI group began to rise at 3rd hour after operation.At 12th and 24th after operation,the brain water content of HT group and CI group was (85.16±0.64)% versus (84.80±0.74)%,(85.20±0.63)% versus (85.47±1.04)%,which present a significant rising.Comparisons showed that HT group and CI group were higher than Sham group at each time point after operation (P<0.05), but HT group and CI group present no significant difference (P>0.05).3 Brain ATPase activity comparisons showed that there was no significant difference between HT group and CI group 3 to 6 hours (P>0.05), but HT group(46.24±8.82,26.84±3.26) was higher than CI group(27.77±6.14,19.21±3.67) 12 to 24 hours (P<0.05).GH group(36.65±3.61,27.45±4.65,22.93±7.14,19.60±4.07) was lower than HT group(37.86±2.84,45.20±5.27,46.24±8.82,26.84±3.26) 6 to 24 hours (P<0.01), and GH group(36.65±3.61,27.45±4.65) was lower than CI group(36.67±1.25,43.40±4.87) 3 to 6 hours (P<0.01),but was no significant different from CI group 12 to 24 hours (P>0.05).4 Brain SDH activity comparisons showed that there was no significant difference among HT group,CI group and GH group at 3rd hour (P>0.05).HT group(0.54±0.08,0.56±0.05) and CI group(0.56±0.03,0.59±0.03) were higher than GH group(0.45±0.04,0.47±0.01) 6 to 12 hours (P<0.05), when there was no significant difference between HT group and CI group (P>0.05).At 24th hour after operation, HT group(0.55±0.05) was higher than CI group(0.45±0.07) and GH group(0.44±0.08) (P<0.05), but there was no significant different between CI group and GH group (P>0.05).5 MDA content of HT group(3.96±0.44) was lower than that of CI group(5.57±0.51) and GH group (5.62±0.49) at 12th hour (P<0.01), but there was no significant difference among HT group, CI group and GH group at 24th hour (P>0.05).6 The brain samples of HT group stained in TTC at 24th hour after operation showed that the normal brain tissue was red, while the infarcted area was white where a hematoma was seen.7 Histological findings in HT group at 24th hour after operation included neuronal degeneration,tissue edema etc under light microscope,ultrastructural change included mitochondrial swelling and endoplasmic reticular dilation.Conclusions: HT model created by two steps in rats was practical and reproducible. A moderate HT in early stage of CI did not aggravate brain edema and neurobehavior,and postponed the brain injury,which could be reflect well with brain ATPase activity, SDH activity and MDA content,and KATP channels contributed to it.The blood invasion played a similar role as a KATP channels opener.A moderate HT would not aggravate CI, which was consistent with documented clinical studies.
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