Paradoxical Motor Recovery From a First Stroke After Induction of a Second Stroke: Reopening a Postischemic Sensitive Period
Open accessAbstract
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.
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Early rehabilitation is recommended in international clinical guidelines based on the notion of a 'window of plasticity' opened by recent ischemia, demonstrated in animal motor recovery experiments.
“Regarding timing of therapy in relation to stroke onset, early rehabilitation is recommended in a number of clinical guidelines internationally. This is based on the notion of a ‘window of plasticity’ that is ‘opened’ by recent ischemia, which has been demonstrated in animal experiments in the sphere of motor recovery [22].”
From Aphasia Recovery: When, How and Who to Treat? (2018) · cites this paper as [22]
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- Authors
- Zeiler, S. R., Hubbard, R., Gibson, E. M., Zheng, T., Ng, K., O’Brien, R., & Krakauer, J. W.
- Affiliations
- Johns Hopkins University (US)
- University of California, Los Angeles (US)
- Duke University (US)
- Corresponding author
- Zeiler, Steven R.
- Venue
- Neurorehabilitation and Neural Repair
- Publisher
- SAGE Publications
- Published
- 2016-07-10
- Volume
- 30
- Issue
- 8
- Pages
- 794-800
- ISSN
- 0888-4390 (ISSN-L)
- 1545-9683
- 1552-6844
- PMC
- PMC4930432
- OpenAlex
- W2340536965
- Cited by
- 97
- References
- 43
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 11 · 2023: 12 · 2022: 6 · 2021: 11 · 2020: 15 · 2019: 9 · 2018: 8 · 2017: 10 · 2016: 2
- FWCI
- 6.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurorehabilitation and neural repair (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- James S. McDonnell Foundation (220020220)
- Johns Hopkins University
- National Institutes of Health (7r01ns052804-05)
- National Institute of Neurological Disorders and Stroke (K08NS085033, R01NS-052804)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD073147)
- Topics
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Life Sciences › Neuroscience › Cognitive Neuroscience › Motor Control and Adaptation
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- stroke recovery, sensitive period, motor training, reach-to-grasp, grasping, motor reorganization, ischemia
- MeSH terms
- Stroke Rehabilitation, Animals, Disease Models, Animal, Functional Laterality, Male, Mice, Inbred C57BL, Motor Cortex, Movement Disorders, Recovery of Function, Stroke, Mice
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