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.
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.
Authors: Juan C Cortes; Jeff Goldsmith; Michelle D Harran; Jing Xu; Nathan Kim; Heidi M Schambra; Andreas R Luft; Pablo Celnik; John W Krakauer; Tomoko Kitago Journal: Neurorehabil Neural Repair Date: 2017-03-16 Impact factor: 3.919
Authors: Brenton Hordacre; Duncan Austin; Katlyn E Brown; Lynton Graetz; Isabel Pareés; Stefania De Trane; Ann-Maree Vallence; Simon Koblar; Timothy Kleinig; Michelle N McDonnell; Richard Greenwood; Michael C Ridding; John C Rothwell Journal: Neurorehabil Neural Repair Date: 2021-02-12 Impact factor: 3.919
Authors: Robert M Hardwick; Vikram A Rajan; Amy J Bastian; John W Krakauer; Pablo A Celnik Journal: Neurorehabil Neural Repair Date: 2016-10-28 Impact factor: 3.919