Effects of Electro-acupuncture Preconditioning on Focal Cerebral Blood Flow in Artery and Vein of Rats with Middle Cerebral Artery Occlusion

In the middle cerebral artery occlusion model of ischemic injury, inlfammation primarily occurs in the infarct and peripheral zones. In the ischemic zone, neurons undergo necrosis and apop-tosis, and a large number of reactive microglia are present. In the present study, we investigated the pathological changes in a rat model of middle cerebral artery occlusion. Neuronal necrosis appeared 12 hours after middle cerebral artery occlusion, and the peak of neuronal apoptosis ap-peared 4 to 6 days after middle cerebral artery occlusion. Inlfammatory cytokines and microglia play a role in damage and repair after middle cerebral artery occlusion. Serum intercellular cell adhesion molecule-1 levels were positively correlated with the permeability of the blood-brain barrier. These ifndings indicate that intercellular cell adhesion molecule-1 may be involved in blood-brain barrier injury, microglial activation, and neuronal apoptosis. Inhibiting blood-brain barrier leakage may alleviate neuronal injury following ischemia.

Tongxinluo has been widely used in China for the treatment of acute stroke and for neu-roprotection. However, there are few positron emission tomography (PET) studies on the neuroprotective effect ofTongxinluo on cerebral ischemia/reperfusion in small animals. In the present study,Tongxinluosuperfine powder suspension or its vehicle was administered intragastrically to rats for 5 successive days before middle cerebral artery occlusion.18F-lfuo-rodeoxyglucose (FDG) small animal PET imaging showed that at 1 and 2 weeks after cerebral ischemia/reperfusion, glucose metabolism in the ischemic area was greater in rats that had receivedTongxinluo than in those that had received the vehicle. Nissl staining showed that 2 weeks after cerebral ischemia/reperfusion, there was less neuronal loss in the prefrontal cortex in Tongxinluo-treated rats than in controls. In addition,Tongxinluo-treated animals showed better neurologic function and lower cerebral infarct volume than rats that received the vehicle. These findings suggest thatTongxinluo exhibits neuroprotective effects in cerebral ischemia/reper-fusion injury and demonstrates that18F-FDG small animal PET imaging is a useful tool with which to study the molecular pharmacology of traditional Chinese medicine.

Aquaporin-4 regulates water molecule channels and is important in tissue regulation and water transportation in the brain. Upregulation of aquaporin-4 expression is closely related to cel-lular edema after early cerebral infarction. Cellular edema and aquaporin-4 expression can be determined by measuring cerebral infarct area and apparent diffusion coefficient using diffu-sion-weighted imaging (DWI). We examined the effects of silencing aquaporin-4 on cerebral infarction. Rat models of cerebral infarction were established by occlusion of the right middle cerebral artery and siRNA-aquaporin-4 was immediately injectedvia the right basal ganglia. In control animals, the area of high signal intensity and relative apparent diffusion coefifcient value on T2-weighted imaging (T2WI) and DWI gradually increased within 0.5–6 hours after cerebral infarction. After aquaporin-4 gene silencing, the area of high signal intensity on T2WI and DWI reduced, relative apparent diffusion coefifcient value was increased, and cellular edema was ob-viously alleviated. At 6 hours after cerebral infarction, the apparent diffusion coefifcient value was similar between treatment and model groups, but angioedema was still obvious in the treat-ment group. These results indicate that aquaporin-4 gene silencing can effectively relieve cellular edema after early cerebral infarction; and when conducted accurately and on time, the diffusion coefifcient value and the area of high signal intensity on T2WI and DWI can relfect therapeutic effects of aquaporin-4 gene silencing on cellular edema.

The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial ifbrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identiifed using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromode-oxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial ifbrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our ifndings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

比较线栓法和电凝法制作小鼠大脑中动脉栓塞模型

目的:目前制作脑缺血模型的的方法主要包括四血管栓塞法、线栓法、光化学法等,每种方法都各有利弊.为了制作一个适合细胞移植治疗缺血性脑损伤的动物模型,本实验比较了电凝法和线栓法制作的小鼠大脑中动脉栓塞模型.方法:本实验采用电凝法和线栓法建立小鼠大脑中动脉栓塞模型.氯化三苯基四氮唑染色确定缺血坏死区.行为学实验评价模型的效果.结果:电凝组缺血坏死区局限在小鼠大脑皮质,而线栓法小鼠缺血坏死区的位置不恒定,而且成活率非常低,不能满足进一步的实验需求.在角落实验与圆筒实验,电凝组与假手术组之间有明显的行为学差异.结论:电凝法可成功建立大脑中动脉栓塞模型,为细胞移植治疗缺血性脑损伤奠定基础.