Stratification substantially reduces behavioral variability in the hypoxic-ischemic stroke model

Julia Pollak, Kristian P. Doyle, Lauren Mamer, Mehrdad Shamloo, Marion S. Buckwalter

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Stroke is the most common cause of long-term disability, and there are no known drug therapies to improve recovery after stroke. To understand how successful recovery occurs, dissect candidate molecular pathways, and test new therapies, there is a need for multiple distinct mouse stroke models, in which the parameters of recovery after stroke are well defined. Hypoxic-ischemic stroke is a well-established stroke model, but behavioral recovery in this model is not well described. We therefore examined a panel of behavioral tests to see whether they could be used to quantify functional recovery after hypoxic-ischemic stroke. We found that in C57BL/6J mice this stroke model produces high mortality (approximately one-third) and variable stroke sizes, but is fast and easy to perform on a large number of mice. Horizontal ladder test performance on day 1 after stroke was highly and reproducibly correlated with stroke size (P<0.0001, R 2 =0.7652), and allowed for functional stratification of mice into a group with >18% foot faults and 2.1-fold larger strokes. This group exhibited significant functional deficits for as long as 3weeks on the horizontal ladder test and through the last day of testing on automated gait analysis (33days), rotarod (30days), and elevated body swing test (EBST) (36days). No deficits were observed in an automated activity chamber. We conclude that stratification by horizontal ladder test performance on day 1 identifies a subset of mice in which functional recovery from hypoxic-ischemic stroke can be studied.

Original languageEnglish (US)
Pages (from-to)698-706
Number of pages9
JournalBrain and Behavior
Issue number5
StatePublished - Sep 2012


  • Behavior
  • Hypoxic-ischemic stroke
  • Motor recovery
  • Mouse model

ASJC Scopus subject areas

  • Behavioral Neuroscience


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