Middle cerebral artery occlusion methods in rat versus mouse model of transient focal cerebral ischemic stroke

Experimental stroke research commonly employs focal cerebral ischemic rat models （Bederson et al., 1986a; Longa et al., 1989）. In human patients, ischemic stroke typically results from thrombotic or embolic occlusion of a major cerebral artery, usually the mid- dle cerebral artery （MCA）. Experimental focal cerebral ischemia models have been employed to mimic human stroke （Durukan and Tatlisumak, 2007）. Rodent models of focal cerebral ischemia that do not require craniotomy have been developed using intraluminal suture occlusion of the MCA （MCA occlusion, MCAO） （Rosamond et al., 2008）. Furthermore, mouse MCAO models have been wide- ly used and extended to genetic studies of cell death or recovery mechanisms （Liu and McCullough, 2011）. Genetically engineered mouse stroke models are particularly useful for evaluation of isch- emic pathophysiology and the design of new prophylactic, neuro- protective, and therapeutic agents and interventions （Armstead et al., 2010）. During the past two decades, MCAO surgical techniques have been developed that do not reveal surgical techniques for mouse MCAO model engineering. Therefore, we compared MCAO surgical methods in rats and mice.

Effects of NG-nitro-L-arginine on focal cerebral ischemic injury in rats

BACKGROUND： Previous researches have proved that aminoguanidin can cure cerebral ischemic injury remarkably as a selective induced nitricoxide synthase （iNOS） inhibitor. However, whether nonselective NOS inhibitor could protect cerebral ischemic injury or not is unclear. OBJECTIVE： To investigate the effects of NG-nitro-L-arginine （L-NA）, a nonselective nitricoxide synthase （NOS） inhibitor, on cerebral ischemic injury of rats and the possible mechanism.DESIGN： Randomized controlled study.SETTING ： Pharmacological Department of Medical Academy of Science of Hebei Province.MATERIALS： A total of 56 male healthy SD rats, of grade Ⅱ, weighting 250-290 g, were provided by the Experimental Animal Center of Hebei Province （certification： 04036）. METHODS： The experiment was completed in the Pharmacological Department of Medical Academy of Science of Hebei Province from March 2005 to January 2006.① Grouping： Rats were randomly divided into 3 groups： sham operation group （n=8）, model group （n=24） and L-NA group （n=24）.② Modeling： Middle cerebral artery （MCA） was established on rats in model group and L-NA group with intreluminal line occlusion methods, and rats in sham operation group were separated their external carotid arteries without occlusion of internal carotid artery. ③ Intervention study： Rats in model group and L-NA group were injected intreperitoneally with 10 mL/kg and 20 mg/kg L-NA at 2, 6 and 12 hours respectively after ischemia twice a day for 3 consecutive days. ④ Rats were sacrificed on the third day for measuring volume of cerebral infarction with image analysis and swelling degrees and activities of mitochondria with electron microscope. Effect of L-NA on ultrastructural changes of neurons in cortex was observed after ischemia. MAIN OUTCOME MEASURES：① Volume of cerebral infarction; ②Swelling degrees, contents of nitric oxide （NO） and malondialdehyde （MDA） and activities of adenosine triphosphatase （ATPase）, superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in mitochondria;③ Ultrastructural changes of mitochondria in brain tissue after cerebral ischemia. RESULTS： ① At 12 hour after ischemia, volume of cerebral infarction in L-NA group was lower than that in model group （P 〈 0.01）. ② Content of NO in mitochondria in L-NA group was decreased as compared with that in model group at 2, 6 and 12 hours after ischemia （P 〈 0.05）; swelling degree of mitochondria in brain tissue was relieved in L-NA group at 12 hour after ischemia, and content of MDA was decreased （P 〈 0.05）; mitochondrial activity in L-NA group was increased at 12 hour after ischemia, and activities of ATPase, SOD and GSH-Px in mitochondria were increased （P 〈 0.05）.③ Degrees of mitochondrial injury in brain tissue were relieved in L-NA group at 12 hour after ischemia as compared with those in model group and L-NA group at 2 and 6 hours after ischemia. CONCLUSION ： ①L-NA can beneficially inhibit NO production, but not protect brain against damage in ischemia acute stage. ②L-NA might have protective effects on cerebral injury through inhibiting the production of oxygen free radical, increasing antioxidation, ameliorating energy metabolism, beneficially improving the integrity of form and function of mitochondria in brain tissue during postischemia in rats.

Buyang Huanwu Decoction(补阳还五汤) Reduces Infarct Volume and Enhances Estradiol and Estradiol Receptor Concentration in Ovariectomized Rats after Middle Cerebral Artery Occlusion

Objective：To investigate the effect of Buyang Huanwu Decoction（补阳还五汤,BYHWD） on estradiol（E2） and estradiol receptor（ER） in serum and brain in ovariectomized rats after middle cerebral artery occlusion（MCAO）.Methods：Adult female rats were ovariectomized and focal cerebral ischemic was induced by MCAO.Rats were randomly divided into normal,ovariectomy（OVX）,MCAO,OVX＋MCAO,OVX＋MCAO＋E2,and OVX＋MCAO＋BYHWD group.Rats were administered BYHWD 5 g/kg daily,estradiol valerate 500 μg/kg per day or distilled water for 7 consecutive days.Neuronal function and infarct volume were measured on day 7 after artery occlusion,and E2 and ER concentration in serum and brain were checked by enzyme-linked immunosorbent assay.Results：BYHWD significantly improved the neurological behavior,reduced the infarction volume,increased E2concentration in serum and brain,and increased ER concentration in the brain in ovariectomized rats after MCAO.Conclusion：The neuroprotective effects of BYHWD are associated with estrogen and its receptor.