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.

Neurite Orientation Dispersion and Density Imaging of Rat Brain Microstructural Changes due to Middle Cerebral Artery Occlusion at a 3T MRI

The purpose of this work was to demonstrate the feasibility of neurite orientation dispersion and density imaging(NODDI)in characterizing the brain tissue microstructural changes of middle cerebral artery occlusion(MCAO)in rats at 3T MRI,and to validate NODDI metrics with histology.A multi-shell diffusion MRI protocol was performed on 11 MCAO rats and 10 control rats at different post-operation time points of 0.5,2,6,12,24 and 72 h.NODDI orientation dispersion index(ODI)and intracellular volume fraction(V_(ic))metrics were compared between MCAO group and control group.The evolution of NODDI metrics was characterized and validated by histology.Infarction was consistent with significantly increased ODI and V_(ic)in comparison to control tissues at all time points(P<0.001).Lesion ODI increased gradually from 0.5 to 72 h,while its V_(ic)showed a more complicated and fluctuated evolution.ODI and V_(ic)were significantly different between hyperacute and acute stroke periods(P<0.001).The NODDI metrics were found to be consistent with the histological findings.In conclusion,NODDI can reflect microstructural changes of brain tissues in MCAO rats at 3T MRI and the metrics are consistent with histology.This study helps to prepare NODDI for the diagnosis and management of ischemic stroke in translational research and clinical practice.

Electrical stimulation upregulates angiopoietin-1/Tie-2 mRNA expression in a rat model of focal cerebral ischemia

Angiopoietin-1/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 （Tie-2） is a newly discovered signaling pathway of angiogenesis. Angiogenesis benefits recovery of neurological functions such as swallowing. In the present study, a rat model of dysphagia following stroke was induced by middle cerebral artery occlusion to investigate the influence of low frequency electrical stimulus with bidirectional square waves and triangular waves on angiopoietin-1/-13e-2 mRNA expression. Reverse transcription-polymerase chain reaction results showed that low frequency electrical stimulus significantly improved the neurological scores of the model rats, and increased angiopoietin-1/＇13e-2 mRNA expression. This demonstrates that low frequency electrical stimulation can ameliorate neurological function in rats with focal brain ischemia, potentially through regulation of angiopoietin-1/-13e-2 expression in the angiogenesis pathway.

Nonhuman primate models of focal cerebral ischemia

Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.

Cluster Analysis for Acupoint Specificity of Acupuncture Effect Based on Cerebral Infarction Rat Model

Objectives： To study the acupoint specificity through the comprehensive evaluation of the acupuncture effect on rat model with the middle cerebral artery occlusion （MCAO）. Methods： Duplicated MCAO model by Zea-longa＇s thread ligation was assessed by Zausinger＇s six-point method, and rats with 1-3 scores were chosen to be grouped. According to the randomized and controlled principle, rats were divided into 6 basic control groups （including normal group, sham group, model control group, model group without intervention, Nimodipine group, lateral-to-Renzhong group） and 6 acupuncture groups [including Neiguan （PC6） group, Weizhong （BL40） group, Chize （LU5） group, Sanyinjiao （SP6） group, Renzhong （DU6） group and non-acupoint group]; in each acupoint or non-acupoint 9 different parameter combinations were respectively set by orthogonal intersection method. There were in total 60 groups, and each group had 12 rats. The rats were treated by acupuncture with the lifting-thrusting manipulation every 12 h, in total 6 times. Indices of neurobehavioral scores, cerebral blood flow, infarction rate, microcirculation, and light microscope, etc. were measured. In order to comprehensively evaluate the acupuncture effect to research the specificity of acupoint, a cluster analysis was made with SPSS17.0 for the comprehensive effect scores of the samples computed according to the comprehensive evaluation models, and then sorting and classification were made for the comprehensive effect scores. Results： In the acupuncture groups every acupoint had different therapeutic effect due to different acupuncture parameter combinations; among the acupuncture groups the orders of curative effect were as followings： Neiguan group was of exceptional result, Weizhong group and Sanyinjiao group were of valid results in upper level, Chize group and Renzhong group were of valid results in lower level, and non-acupoint group was of invalid result; the therapeutic result of acupoint group was superior to non-acupoint group; and the curative effect of acupuncture group was also superior to basic control group. Conclusion： The acupoint has the specificity of acupuncture effect, and the acupoint specificity is relative.