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

25 Citations (Scopus)

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

Fingerprint

Stroke
Forelimb
Ischemia
Light Coagulation
Motor Cortex
Hand Strength

Keywords

  • motor
  • recovery
  • sensitive period
  • stroke

ASJC Scopus subject areas

  • Rehabilitation
  • Neurology
  • Clinical Neurology

Cite this

Paradoxical motor recovery from a first stroke after induction of a second stroke : Reopening a postischemic sensitive period. / Zeiler, Steven R.; Hubbard, Robert; Gibson, Ellen M.; Zheng, Tony; Ng, Kwan; O'Brien, Richard; Krakauer, John W.

In: Neurorehabilitation and Neural Repair, Vol. 30, No. 8, 01.09.2016, p. 794-800.

Research output: Contribution to journalArticle

Zeiler, Steven R. ; Hubbard, Robert ; Gibson, Ellen M. ; Zheng, Tony ; Ng, Kwan ; O'Brien, Richard ; Krakauer, John W. / Paradoxical motor recovery from a first stroke after induction of a second stroke : Reopening a postischemic sensitive period. In: Neurorehabilitation and Neural Repair. 2016 ; Vol. 30, No. 8. pp. 794-800.
@article{1e3e06781c3e4518b43c1e5c132e8e45,
title = "Paradoxical motor recovery from a first stroke after induction of a second stroke: Reopening a postischemic sensitive period",
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.",
keywords = "motor, recovery, sensitive period, stroke",
author = "Zeiler, {Steven R.} and Robert Hubbard and Gibson, {Ellen M.} and Tony Zheng and Kwan Ng and Richard O'Brien and Krakauer, {John W.}",
year = "2016",
month = "9",
day = "1",
doi = "10.1177/1545968315624783",
language = "English (US)",
volume = "30",
pages = "794--800",
journal = "Neurorehabilitation and Neural Repair",
issn = "1545-9683",
publisher = "SAGE Publications Inc.",
number = "8",

}

TY - JOUR

T1 - Paradoxical motor recovery from a first stroke after induction of a second stroke

T2 - Reopening a postischemic sensitive period

AU - Zeiler, Steven R.

AU - Hubbard, Robert

AU - Gibson, Ellen M.

AU - Zheng, Tony

AU - Ng, Kwan

AU - O'Brien, Richard

AU - Krakauer, John W.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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.

AB - 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.

KW - motor

KW - recovery

KW - sensitive period

KW - stroke

UR - http://www.scopus.com/inward/record.url?scp=84981342026&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84981342026&partnerID=8YFLogxK

U2 - 10.1177/1545968315624783

DO - 10.1177/1545968315624783

M3 - Article

C2 - 26721868

AN - SCOPUS:84981342026

VL - 30

SP - 794

EP - 800

JO - Neurorehabilitation and Neural Repair

JF - Neurorehabilitation and Neural Repair

SN - 1545-9683

IS - 8

ER -