Delayed treatment with chondroitinase ABC promotes sensorimotor recovery and plasticity after stroke in aged rats
Open accessAbstract
Stroke is the dominant cause of sensorimotor disability that primarily affects the elderly. We now show that neuroplasticity and functional recovery after stroke is constrained by inhibitory chondroitin sulphates. In two blinded, randomized preclinical trials, degradation of chondroitin sulphate using chondroitinase ABC reactivated neuroplasticity and promoted sensorimotor recovery after stroke in elderly rats. Three days after stroke, chondroitinase ABC was microinjected into the cervical spinal cord to induce localized plasticity of forelimb sensorimotor spinal circuitry. Chondroitinase ABC effectively removed chondroitin sulphate from the extracellular matrix and perineuronal nets. Three different tests of sensorimotor function showed that chondroitinase ABC promoted recovery of forelimb function. Anterograde and retrograde tracing showed that chondroitinase ABC also induced sprouting of the contralesional corticospinal tract in the aged treated hemicord. Chondroitinase ABC did not neuroprotect the peri-infarct region. We show for the first time delayed chondroitinase ABC treatment promotes neuroanatomical and functional recovery after focal ischaemic stroke in an elderly nervous system.
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Following experimentally induced stroke in aged rats, timely fine-tuned delayed treatment with ChABC did not protect the peri-infarct region.
“Following experimentally induced stroke in aged rats, the timely fine-tuned delayed treatment with ChABC promoted functional recovery and neuroplasticity, but did not protect the peri-infarct region (Soleman et al., 2012).”
From Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep (2017) · cites this paper as Soleman et al., 2012
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“The inhibition of CSPGs can be relieved by the bacterial enzyme chondroitinase ABC which removes the chondroitin sulfate chains from the core proteins, thus promoting axonal regeneration/collateral sprouting of a wide variety of neuron tracts and functional recovery after stroke or SCI [49-57].”
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- Authors
- Soleman, S., Yip, P. K., Duricki, D. A., & Moon, L. D. F.
- Affiliations
- King's College London (GB)
- Queen Mary University of London (GB)
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-03-06
- Volume
- 135
- Issue
- 4
- Pages
- 1210-1223
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC5581954
- OpenAlex
- W2116378996
- Cited by
- 123
- References
- 67
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 9 · 2018: 17 · 2017: 18 · 2016: 10 · 2015: 7 · 2014: 12 · 2013: 13 · 2012: 3
- FWCI
- 11.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/E527098/1)
- Topics
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- chondroitinase ABC, chondroitin sulfate, stroke, sensorimotor recovery, neuroplasticity, aged rats, spinal cord, perineuronal nets, extracellular matrix, forelimb function, treatment delay
- MeSH terms
- Acoustic Stimulation, Aging, Amidines, Analysis of Variance, Animals, Biotin, Dextrans, Disease Models, Animal, Double-Blind Method, Female, Forelimb, Injections, Spinal, Functional Laterality, Male, Movement Disorders, Neuronal Plasticity, Neurons, Chondroitin Sulfate Proteoglycans, Psychomotor Performance, Pyramidal Tracts, Sensation Disorders, Time Factors, Chondroitin ABC Lyase, Recovery of Function, Gait Disorders, Neurologic, Rats, Long-Evans, Brain Infarction, Stroke, Receptors, N-Acetylglucosamine, Plant Lectins, Rats
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