Animal Models of Ischemic Stroke. Part One: Modeling Risk Factors

Marco Bacigaluppi

doi:10.2174/1874205x01004010026

Abstract

Ischemic stroke is one of the leading causes of long-term disability and death in developed and developing countries. As emerging disease, stroke related mortality and morbidity is going to step up in the next decades. This is both due to the poor identification of risk factors and persistence of unhealthy habits, as well as to the aging of the population. To counteract the estimated increase in stroke incidence, it is of primary importance to identify risk factors, study their effects, to promote primary and secondary prevention, and to extend the therapeutic repertoire that is currently limited to the very first hours after stroke. While epidemiologic studies in the human population are essential to identify emerging risk factors, adequate animal models represent a fundamental tool to dissect stroke risk factors to their molecular mechanism and to find efficacious therapeutic strategies for this complex multi- factorial disorder. The present review is organized into two parts: the first part deals with the animal models that have been developed to study stroke and its related risk factors and the second part analyzes the specific stroke models. These models represent an indispensable tool to investigate the mechanisms of cerebral injury and to develop novel therapies.

Highlights

Stroke represents the leading cause of long-term disability and second-frequent cause of mortality among all causes of death (behind cardiovascular diseases (CVD)) (National Center for Health Statistics, http://www.cdc.gov/nchs/fastats/ deaths.htm) [1]
This is due to the increase in the mean population age, the persistence and the increase of unhealthy life habits, including physical inactivity, tobacco smoking, excessive and unhealthy food resulting in obesity, arterial hypertension, hypercholesterolemia and type II diabetes affecting in particular young patients, in both industrialized and developing countries [2] [World Health Organization, http://www.who.int/cardiovascular_diseases/resources/ atlas/en]
The models described in i.) and ii.) are used to study the relationship between risk factors and stroke with the overall aim to understand and to develop efficacious treatments to avoid the occurrence of cerebral ischemic damage

Summary

INTRODUCTION

Stroke represents the leading cause of long-term disability and second-frequent cause of mortality among all causes of death (behind cardiovascular diseases (CVD)) (National Center for Health Statistics, http://www.cdc.gov/nchs/fastats/ deaths.htm) [1]. In vitro systems alone cannot thoroughly evaluate stroke and its consequences, given the importance of the brain vasculature to study the effects of abnormal brain perfusion and given the involvement of other systems as well [5] For these reasons animal models are required to reproduce specific aspects of human disease, to understand the complex pathophysiology of stroke and to find efficacious preventive and therapeutic approaches [6, 7]. The models described in i.) and ii.) are used to study the relationship between risk factors (modifiable and not modifiable) and stroke with the overall aim to understand and to develop efficacious treatments to avoid the occurrence of cerebral ischemic damage In these models, variables can be taken under strict control and researchers may address specific questions about pathologic events leading to stroke [8]

Atherosclerosis and Associated Risk Factors

CADASIL transgenic mouse

Aging as Risk Factor for Stroke

Findings

CONCLUSION