A modified bilateral carotid artery stenosis procedure to develop a chronic cerebral hypoperfusion rat model with an increased survival rate

Nan Li; Zhiqiang Gu; Yunfei Li; Xiaojie Fu; Jianping Wang; Hongying Bai

doi:10.1016/j.jneumeth.2015.08.002

A modified bilateral carotid artery stenosis procedure to develop a chronic cerebral hypoperfusion rat model with an increased survival rate

J Neurosci Methods. 2015 Nov 30:255:115-21. doi: 10.1016/j.jneumeth.2015.08.002. Epub 2015 Aug 13.

Authors

Nan Li¹, Zhiqiang Gu², Yunfei Li³, Xiaojie Fu⁴, Jianping Wang⁵, Hongying Bai⁶

Affiliations

¹ Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
² Department of Radiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
³ Department of Radiology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
⁴ Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
⁵ Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: wjpwfy666@126.com.
⁶ Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: drbaihongying@yeah.com.

PMID: 26277419
DOI: 10.1016/j.jneumeth.2015.08.002

Abstract

Background: Bilateral carotid artery occlusion (2-vessel occlusion, 2VO) in rats is a classic and frequently used approach to develop an animal model of chronic cerebral hypoperfusion. However, this method results in substantial mortality in rats.

New method: We investigated whether a modified 2VO procedure, which induces bilateral carotid artery stenosis via ligation of each bilateral common carotid artery (CCA) with a 32 gauge (G) needle followed by needle removal, could produce a chronic cerebral hypoperfusion rat model with an increased survival rate. Sprague-Dawley (SD) rats were treated with the standard or modified 2VO procedure, and changes in cerebral blood flow (CBF) and survival rates were determined. On day 28, cognitive function was assessed with the Morris Water Maze (MWM) test, and neuronal survival and degeneration within the hippocampal CA1 area were measured. Damage to the white matter (WM) within the corpus striatum was assessed via Luxol fast blue (LFB) staining and analyses analyzing the levels of the myelin basic protein (MBP) protein levels.

Results: The modified 2VO procedure induced similar cognitive impairments, hippocampal lesions and WM damage compared with the standard 2VO procedure in rats; however, it had an increased survival rate. Comparison with existing methods This novel method can be used to quickly and effectively establish a chronic cerebral hypoperfusion rat model with common materials and an improved survival rate.

Conclusion: Bilateral carotid artery stenosis using a 32 G needle is a useful and reliable method to develop a rat model of chronic cerebral hypoperfusion with increased survival.

Keywords: 2VO; Chronic cerebral hypoperfusion model.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
CA1 Region, Hippocampal / pathology
Carotid Artery, Common / surgery*
Carotid Stenosis* / mortality
Carotid Stenosis* / pathology
Carotid Stenosis* / psychology
Chronic Disease
Corpus Striatum / metabolism
Corpus Striatum / pathology
Disease Models, Animal*
Functional Laterality
Ligation / instrumentation
Ligation / methods
Male
Maze Learning
Myelin Basic Protein / metabolism
Needles
Neurons / pathology
Neurosurgical Procedures* / instrumentation
Rats, Sprague-Dawley
White Matter / metabolism
White Matter / pathology

Substances

Myelin Basic Protein