Article

Original Article

Exp Neurobiol 2014; 23(1): 104-114

Published online March 30, 2014

https://doi.org/10.5607/en.2014.23.1.104

© The Korean Society for Brain and Neural Sciences

A Method for Generate a Mouse Model of Stroke: Evaluation of Parameters for Blood Flow,
Behavior, and Survival

Sin-Young Park1,2#, Subash Marasini1,2#, Geu-Hee Kim1,2#, Taeyun Ku4, Chulhee Choi4, Min-Young Park5, Eun-Hee Kim5, Young-Don Lee1,2,3, Haeyoung Suh-Kim1,2 and Sung-Soo Kim1,3*

1Department of Anatomy, 2Neuroscience Graduate Program, and 3Center for Cell Death Regulating Biodrug, Ajou University School of Medicine, Suwon 443-380, 4Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, 5College of Bioscience and Biotechnology, Chungnam National University, Daejeon 305-764, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-31-219-5034, FAX: 82-31-219-5039
e-mail: kimdmg@ajou.ac.kr
#These authors are equally contributed to this work.

Received: February 21, 2014; Revised: February 27, 2014; Accepted: February 27, 2014

Abstract

Stroke is one of the common causes of death and disability. Despite extensive efforts in stroke research, therapeutic options for improving the functional recovery remain limited in clinical practice. Experimental stroke models using genetically modified mice could aid in unraveling the complex pathophysiology triggered by ischemic brain injury. Here, we optimized the procedure for generating mouse stroke model using an intraluminal suture in the middle cerebral artery and verified the blockage of blood flow using indocyanine green coupled with near infra-red radiation. The first week after the ischemic injury was critical for survivability. The survival rate of 11% in mice without any treatment but increased to 60% on administering prophylactic antibiotics. During this period, mice showed severe functional impairment but recovered spontaneously starting from the second week onward. Among the various behavioral tests, the pole tests and neurological severity score tests remained reliable up to 4 weeks after ischemia, whereas the rotarod and corner tests became less sensitive for assessing the severity of ischemic injury with time. Further, loss of body weight was also observed for up 4 weeks after ischemia induction. In conclusion, we have developed an improved approach which allows us to investigate the role of the cell death-related genes in the disease progression using genetically modified mice and to evaluate the modes of action of candidate drugs.

Keywords: blood flow, middle cerebral artery, survival, stroke, brain ischemia, behavior