The Study Of ET-1 Induced Ischemic Stroke Model And Post-injury Recovery In Finger Motor Area Of Macaque

ObjectiveIschemic stroke is one of the killers of human health, which has characteristics of high incidence, high mortality rate and disability rate, brought a heavy burden for the community and family. Currently there is no effective treatment for ischemic stroke which is mortality and disability rate continues to increase, in-depth study of the damage mechanism and treatment strategies of ischemic stroke have important scientific significance. In recent years, studies have shown that the mechanism of endothelin-1 (Endothelin-1, ET-1) induced ischemic brain injury is similar to the human stroke and macaque brain blood vessels and brain tissue of cerebral ischemia reaction closest human stroke. Therefore, the present study use ET-1 that can cause partial contraction of vascular to production macaque models of local stroke closest to human ischemic stroke, in order to study the function damage and repair of ischemic stroke, providing stable animal models for preclinical research on treatment of ischemic stroke.MethodsWe use two Ganges macaques (Macaca mulatta) to produce cerebral ischemia model. Prior to the injury, two rhesus monkeys were trained and tested with Kluver board task, vertical slots task and Rotating Brinkman board task such as grabing food. Experiment was divided into two parts:the first part is a small dose of ET-1 (5μg/ 10μl × 5 injection sites) induced ischemic injury in finger motor cortex of two macaque, respectively, magnetic resonance imaging (MRI) in 1 d,7d,14d,28d after the injury, and in 3d,7d,14d,28d after injury using three behavioral tasks to test and record the time of grasping motion to assess damage and recovery of finger dexterity. The second part is when finger dexterity of two macaque were restored to near normal, use large doses of ET-1 (10μg/10μl × 5 injection sites) in which a monkey finger motor cortex induced ischemic injury again, use three behavioral tasks to test after injury 7d,14d,28d to assess the damage and recovery of finger dexterity.ResultsAfter small doses of ET-1 induced ischemic injury in two macaque finger motor cortex, MRI shown a monkey brain lesion volume in the first day after injury reached the maximum, from 7d gradually decreased until 28 days close normal; another monkey was found a large area of brain edema in 7d after injury, after brain edema was decreased gradually, until 28d near normal. In the test of Kluver board task, vertical slots task and Rotating Brinkman board task with macaques grabing food, the number of grabing food was significantly reduced in 3d after injury,7d began to increased, in 14d to near normal levels, while the number of failures in 3d after injury was significantly increased,7d began to decreased, but still increased over preoperative levels. The time of grabing movement completed was significantly longer in 3d and 7d after injury, afterl4d gradually reduced to near normal. Large doses of ET-1 induced injury again which after a monkey finger motor cortex ischemic injury, the number of grabing food was reduced slightly in 7d after injury, in 14d near the preoperative level; the number of failures in 7d after injury was increased slightly, reduced in14d close to the level of preoperation.ConclusionThese results suggest that:1. We use the ET-1-induced ischemic stroke in macaque finger movement area to make animal models is the closest to the human of stroke,which has great scientific significance and clinical value for preclinical studies, but part of the behavioral outcomes lacked statistical support, May be related to insufficient sample size, need further study.2. We use the ET-1 (5μg/10μl×5 injection points) induction ischemic injury in finger motor cortex macaque, MRI shown the volume of brain ischemic injury was largerest in 3d and 7d after injury,after 7dn have been getting better. macaque finger dexterity was injuried obviously in first 7d after the motor cortex damage,until 14d fast restored to near normal levels, consistent with the change in the volume of ischemic brain injury.3. ET-1 (10μg/ 10μl×5 injection points) second induction ischemic injury in macaque finger motor cortex, finger dexterity was no worse than the time after first injury, and 14d to return to preinjury level, may be due to other functional areas play a compensatory role.4. After macaque fingers motor cortex was ischemic injuried, finger dexterity has be significantly improved in 14d after injury, probably because of neurovascular remodeling, compensatory role of other functional areas, resulting in the finger movement with test training, promote the recovery of finger movement functions.