Getting Neurorehabilitation Right: What Can Be Learned From Animal Models?
Open accessAbstract
Animal models suggest that a month of heightened plasticity occurs in the brain after stroke, accompanied by most of the recovery from impairment. This period of peri-infarct and remote plasticity is associated with changes in excitatory/inhibitory balance and the spatial extent and activation of cortical maps and structural remodeling. The best time for experience and training to improve outcome is unclear. In animal models, very early (<5 days from onset) and intense training may lead to increased histological damage. Conversely, late rehabilitation (>30 days) is much less effective both in terms of outcome and morphological changes associated with plasticity. In clinical practice, rehabilitation after disabling stroke involves a relatively brief period of inpatient therapy that does not come close to matching intensity levels investigated in animal models and includes the training of compensatory strategies that have minimal impact on impairment. Current rehabilitation treatments have a disappointingly modest effect on impairment early or late after stroke. Translation from animal models will require the following: (1) substantial increases in the intensity and dosage of treatments offered in the first month after stroke with an emphasis on impairment; (2) combinational approaches such as noninvasive brain stimulation with robotics, based on current understanding of motor learning and brain plasticity; and (3) research that emphasizes mechanistic phase II studies over premature phase III clinical trials.
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Frequent repetition of training (distributed practice) is associated with improved motor learning after stroke.
“Further, frequent repetition of training (distributed practice) is associated with improved motor learning after stroke.9,10”
From Prespecified dose-response analysis for A Very Early Rehabilitation Trial (AVERT) (2016) · cites this paper as [10]
The first 90 days post stroke is the window of opportunity where the greatest potential to harness spontaneous recovery exists.
“Evidence from human motor and animal stroke recovery models suggests the first 90 days post stroke is the ‘window of opportunity’ 2 where the greatest potential to harness spontaneous recovery exists. 12”
From A randomized control trial of intensive aphasia therapy after acute stroke: The Very Early Rehabilitation for SpEech (VERSE) study (2021) · cites this paper as [12]
High frequency repetition should strengthen neural networks and minimize independent neuronal activation, potentially reducing maladaptive behaviors.
“This theory suggests that high frequency repetition should strengthen neural networks and minimize independent neuronal activation, potentially reducing maladaptive behaviors.2,12”
From A randomized control trial of intensive aphasia therapy after acute stroke: The Very Early Rehabilitation for SpEech (VERSE) study (2021) · cites this paper as [12]
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- Authors
- Krakauer, J. W., Carmichael, S. T., Corbett, D., & Wittenberg, G. F.
- Affiliations
- Johns Hopkins University (US)
- University of California, Los Angeles (US)
- University of Ottawa (CA)
- University of Maryland, Baltimore (US)
- Venue
- Neurorehabilitation and Neural Repair
- Publisher
- SAGE Publications
- Published
- 2012-03-30
- Volume
- 26
- Issue
- 8
- Pages
- 923-931
- ISSN
- 0888-4390 (ISSN-L)
- 1545-9683
- 1552-6844
- PMC
- PMC4554531
- OpenAlex
- W2131467344
- Cited by
- 591
- References
- 61
- Citations by year
- 2026: 61 · 2025: 42 · 2024: 32 · 2023: 35 · 2022: 34 · 2021: 52 · 2020: 47 · 2019: 47 · 2018: 32 · 2017: 50 · 2016: 54 · 2015: 32 · 2014: 36 · 2013: 29 · 2012: 7
- FWCI
- 35.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurorehabilitation and neural repair (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Lirias (submittedVersion)
- Funders
- National Institutes of Health (VA999999)
- National Institute on Aging (P30AG028747)
- Topics
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Keywords
- stroke rehabilitation, neuroplasticity, excitation-inhibition balance, cortical reorganization, rehabilitation timing, treatment intensity, animal models of stroke, non-invasive brain stimulation, robot-assisted therapy, motor learning, translational research
- MeSH terms
- Stroke Rehabilitation, Animals, Disease Models, Animal, Humans, Time Factors, Recovery of Function, Brain Infarction, Stroke
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