Paradoxical motor recovery from a first stroke after induction of a second stroke: Reopening a postischemic sensitive period

Steven R. Zeiler, Robert Hubbard, Ellen M. Gibson, Tony Zheng, Kwan Ng, Richard O'Brien, John W. Krakauer

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Background and objective. Prior studies have suggested that after stroke there is a time-limited period of increased responsiveness to training as a result of heightened plasticity - a sensitive period thought to be induced by ischemia itself. Using a mouse model, we have previously shown that most training-associated recovery after a caudal forelimb area (CFA) stroke occurs in the first week and is attributable to reorganization in a medial premotor area (AGm). The existence of a stroke-induced sensitive period leads to the counterintuitive prediction that a second stroke should reopen this window and promote full recovery from the first stroke. To test this prediction, we induced a second stroke in the AGm of mice with incomplete recovery after a first stroke in CFA. Methods. Mice were trained to perform a skilled prehension (reach-to-grasp) task to an asymptotic level of performance, after which they underwent photocoagulation-induced stroke in CFA. After a 7-day poststroke delay, the mice were then retrained to asymptote. We then induced a second stroke in the AGm, and after only a 1-day delay, retrained the mice. Results. Recovery of prehension was incomplete when training was started after a 7-day poststroke delay and continued for 19 days. However, a second focal stroke in the AGm led to a dramatic response to 9 days of training, with full recovery to normal levels of performance. Conclusions. New ischemia can reopen a sensitive period of heightened responsiveness to training and mediate full recovery from a previous stroke.

Original languageEnglish (US)
Pages (from-to)794-800
Number of pages7
JournalNeurorehabilitation and Neural Repair
Volume30
Issue number8
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

Keywords

  • motor
  • recovery
  • sensitive period
  • stroke

ASJC Scopus subject areas

  • Rehabilitation
  • Neurology
  • Clinical Neurology

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