Evaluation For Neurobehavioral And Histopathological Injures Induced By Focal Cerebral Ischemia In Mice

Studies of pathological mechanism of human cerebrovascular disease and discovery of therapeutic drugs need ideal animal models. So, it is neccessary that the alteration of neurobehavioral function of cerebral ischemic animals should be quantified objectively so that the pathological progress and prognosis are estimated precisely. Simple and sensitive indexes should also be established for the evaluation of noval medical therapies to protect the ischemic brain. Cerebral ischemia is a common brain disease with high incidence and deformity and mortality. Prominent clinical manifestation of focal cerebral ischemia is contralateral neurological function deficit, such as hemiplegia. It is reported that Bederson's score mothed, screen test, rotarod performance test and Prehensile-traction test have been used to estimate neurobehavioral function deficit of the animal model of cerebral ischemia . At present, those methods that estimate the neurobehavioral function deficit of cerebral ischemia are rough and lack of quantitative and standardizative estimating system. The main aim of this study was to establish the evaluating method of neurobehavioral function deficit of focal cerebral ischemia. The neurobehavioral function was evaluated by integrated grades of hanging test and climbing board test on computer analysis. The correlation between integrated grades and the volumes of infarcts on focalcerebral ischemia were compared. We tested integrated grades of hanging test and climbing board test as well as Bederson's scores in order to find out more accurate methods which estimate ischemic lesion. We determined integrated grades of hanging test and climbing board test and the volumes of infarcts on focal cerebral ischemia and analysed the correlation between the grades and Bederson's scores in control and ONO-1078 treatd mice.In the present study, persistent focal cerebral ischemia was induced by middle cerebral artery occlusion(MCAO) using intraluminal suture in mice. The neurobehavioral function deficit was quantificationally evaluated by integrated grades of hanging test and climbing board test 24h after the surgery. The neurobehavioral function deficit was also examined by Bederson's mothed. The brains were then removed and coronally disssected into 1mm thick sections. The sections were stained with 0.5%TTC at 37癈 for 30 min and the video images were recorded and stored in the computer. The volumes of infarcts by the TTC staining were calculated using an image analyzer(AnalyPowerl.O). Coronary setions(8 u m) were prepared from fifth brain slice (bregma, -2.0mm), and stained with HE, and the neurons density was obtained by light microscopy.We found that there was a close correlation between integrated grades (hanging test and climbing board test) and the volumes of infarcts by the TTC staining (rs=0.713, PO.001). The integrated grades of hanging test and climbing board test were correlated closely to Bederson's scores (r=0.631t P<0.001). The integrated grades and the volumes of infarcts reduced significantly when mice were treated with ONO-1078.In summary, the integrated grade of hanging test and climbing board test is objective index of neurobehavioral function deficit that is consistent with thevolumes of infarcts in the focal cerebral ischemic mice. The method is alsouesful to evaluate neuroprotective effects of drugs like ONO-1078, and to investigate mechanisms of ischemic injures.