title: Paradoxical Motor Recovery From a First Stroke After Induction of a Second Stroke: Reopening a Postischemic Sensitive Period.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  New ischemia can reopen a sensitive period of heightened responsiveness to training and mediate full recovery from a previous stroke.
authors.affiliation: Johns Hopkins University, Baltimore, MD, USA sz@jhmi.edu.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Zeiler
authors.affiliation: Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Hubbard
authors.affiliation: Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Gibson
authors.affiliation: Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Zheng
authors.affiliation: UCLA, Los Angeles CA, USA.
authors.forename: Kwan
authors.initials: K
authors.lastname: Ng
authors.affiliation: Duke University, Durham, NC, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: O'Brien
authors.affiliation: Johns Hopkins University, Baltimore, MD, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Krakauer
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009044:Motor Cortex / Q000503:physiopathology; D009069:Movement Disorders / Q000209:etiology*; D020127:Recovery of Function / Q000502:physiology*; D020521:Stroke / Q000150:complications* / Q000503:physiopathology; D000071939:Stroke Rehabilitation / Q000009:adverse effects*
keywords: motor; recovery; sensitive period; stroke