Procedural and strain-related variables significantly affect outcome in a murine model of focal cerebral ischemia

E. Sander Connolly, Christopher J. Winfree, David Stern, Robert A. Solomon, David J. Pinsky

Research output: Contribution to journalArticle

181 Citations (Scopus)

Abstract

THE RECENT AVAILABILITY of transgenic mice has led to a burgeoning number of reports describing the effects of specific gene products on the pathophysiology of stroke. Although focal cerebral ischemia models in rats have been well described, descriptions of a murine model of middle cerebral artery occlusion are scant and sources of potential experimental variability remain undefined. We hypothesized that slight technical modifications would produce widely discrepant results in a murine model of stroke and that controlling surgical and procedural conditions could lead to reproducible physiological and anatomic stroke outcomes. To test this hypothesis, we established a murine model that would permit either permanent or transient focal cerebral ischemia by intraluminal occlusion of the middle cerebral artery. This study provides a detailed description of the surgical technique and reveals important differences among strains commonly used in the production of transgenic mice. In addition to strain-related differences, infarct volume, neurological outcome, and cerebral blood flow appear to be importantly affected by temperature during the ischemic and postischemic periods, mouse size, and the size of the suture that obstructs the vascular lumen. When these variables were kept constant, there was remarkable uniformity of stroke outcome. These data emphasize the protective effects of hypothermia in stroke and might help to standardize techniques among different laboratories to provide a cohesive framework for evaluating the results of future studies in transgenic animals.

Original languageEnglish (US)
Pages (from-to)523-532
Number of pages10
JournalNeurosurgery
Volume38
Issue number3
DOIs
StatePublished - Mar 1996
Externally publishedYes

Fingerprint

Brain Ischemia
Stroke
Middle Cerebral Artery Infarction
Transgenic Mice
Cerebrovascular Circulation
Genetically Modified Animals
Transient Ischemic Attack
Hypothermia
Sutures
Blood Vessels
Temperature
Genes

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Surgery

Cite this

Procedural and strain-related variables significantly affect outcome in a murine model of focal cerebral ischemia. / Connolly, E. Sander; Winfree, Christopher J.; Stern, David; Solomon, Robert A.; Pinsky, David J.

In: Neurosurgery, Vol. 38, No. 3, 03.1996, p. 523-532.

Research output: Contribution to journalArticle

Connolly, E. Sander ; Winfree, Christopher J. ; Stern, David ; Solomon, Robert A. ; Pinsky, David J. / Procedural and strain-related variables significantly affect outcome in a murine model of focal cerebral ischemia. In: Neurosurgery. 1996 ; Vol. 38, No. 3. pp. 523-532.
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