Etiology of stroke and choice of models

Paul R. Krafft, Emma L. Bailey, Tim Lekic, William B. Rolland, Orhan Altay, Jiping Tang, Joanna M. Wardlaw, John H. Zhang, Cathie L. M. Sudlow*

*Corresponding author for this work

Research output: Contribution to journalLiterature reviewpeer-review

Abstract

Animal models of stroke contribute to the development of better stroke prevention and treatment through studies investigating the pathophysiology of different stroke subtypes and by testing promising treatments before trials in humans. There are two broad types of animal models: those in which stroke is induced through artificial means, modeling the consequences of a vascular insult but not the vascular pathology itself; and those in which strokes occur spontaneously. Most animal models of stroke are in rodents due to cost, ethical considerations, availability of standardized neurobehavioral assessments, and ease of physiological monitoring. While there are similarities in cerebrovascular anatomy and pathophysiology between rodents and humans, there are also important differences, including brain size, length and structure of perforating arteries, and gray to white matter ratio, which is substantially lower in humans. The wide range of rodent models of stroke includes models of global and focal ischemia, and of intracerebral and sub-arachnoid hemorrhage. The most widely studied model of spontaneous stroke is the spontaneously hypertensive stroke-prone rat, in which the predominant lesions are small subcortical infarcts resulting from a vascular pathology similar to human cerebral small vessel disease. Important limitations of animal models of stroke they generally model only certain aspects of the disease and do not reflect the heterogeneity in severity, pathology and comorbidities of human stroke and key methodological issues (especially the need for adequate sample size, randomization, and blinding in treatment trials) must be carefully considered for the successful translation of pathophysiological concepts and therapeutics from bench to bedside.

Original languageEnglish
Pages (from-to)398-406
Number of pages9
JournalInternational Journal of Stroke
Volume7
Issue number5
DOIs
Publication statusPublished - Jul 2012

Keywords

  • ANIMAL-MODELS
  • ischemic stroke
  • stroke subtypes
  • CARDIAC-ARREST
  • animal models
  • CEREBRAL-ARTERY OCCLUSION
  • FOREBRAIN ISCHEMIA
  • EMBOLIC STROKE
  • intracerebral hemorrhage
  • EXPERIMENTAL SUBARACHNOID HEMORRHAGE
  • sub-arachnoid hemorrhage
  • BLOOD-FLOW
  • rodent
  • TISSUE PLASMINOGEN-ACTIVATOR
  • RODENT MODELS
  • INTRACEREBRAL HEMORRHAGE

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