Delayed anti-Nogo-A therapy improves function after chronic stroke in adult rats
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Background and Purpose—: We have shown that anti-Nogo-A immunotherapy to neutralize the neurite growth inhibitory protein Nogo-A results in functional improvement and enhanced plasticity after ischemic stroke in the adult rat. The present study investigated whether functional improvement and neuronal plasticity can be induced by this immunotherapy when administered to the chronic stroke-impaired rat. Methods—: Adult rats were trained to perform the skilled forelimb reaching test, followed by permanent middle cerebral artery occlusion to impair the preferred forelimb. Nine weeks after stroke, animals showing a profound deficit were randomly distributed to 3 groups: no treatment, control antibody, or anti-Nogo-A antibody (11C7). Animals were tested weekly after stroke surgery and daily after antibody treatment until the end of the study. Biotin dextran amine tracing was injected into the nonlesioned forelimb motor cortex at the end of behavioral testing to determine axonal plasticity. Results—: All rats showed similar forelimb impairment before treatment. Animals treated with anti-Nogo-A immunotherapy started to show improvement 3 weeks after treatment. Such improvement became significantly better than stroke-only control and control Ab-treated animals, and persisted to the end of the study. Biotin dextran amine-labeled axonal fiber analysis also showed significant enhanced corticorubral axonal sprouting from the contralesional forelimb motor cortex to the deafferented red nucleus in the anti-Nogo-A immunotherapy rats. Conclusions—: These results indicate that improvement of chronic neurological deficits and enhancement of neuronal plasticity can be induced in the adult rat with anti-Nogo-A immunotherapy, and that this therapy may be used to restore function even when administered long after ischemic brain damage has occurred.
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In rodents, beneficial effects of neurorestorative treatments were reported even when treatments were initiated days, weeks, or months after stroke.
“In rodents, beneficial effects were reported even when treatments were initiated days, weeks, or months after stroke.14–20”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [20]
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Self-citationAnti-Nogo-A Antibody Therapy Improves Functional Outcome Following Traumatic Brain Injury
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Self-citationChinese Medicine’s Intervention Effect on Nogo-A/NgR
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Self-citation
- Authors
- Tsai, S.-Y., Papadopoulos, C. M., Schwab, M. E., & Kartje, G. L.
- Affiliations
- Loyola University Chicago (US)
- Venue
- Stroke
- Published
- 2011-01
- Volume
- 42
- Issue
- 1
- Pages
- 186-190
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- PMC
- PMC3806087
- OpenAlex
- W2134396069
- Cited by
- 106
- References
- 26
- Citations by year
- 2026: 2 · 2025: 6 · 2023: 4 · 2022: 1 · 2021: 3 · 2020: 7 · 2019: 6 · 2018: 8 · 2017: 12 · 2016: 9 · 2015: 11 · 2014: 11 · 2013: 17 · 2012: 5
- FWCI
- 8.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Stroke (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 RX000828)
- U.S. Public Health Service (40960)
- National Institute of Neurological Disorders and Stroke (R01NS040960, R56NS040960)
- Topics
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Keywords
- Nogo-A, chronic stroke, ischemic stroke, axonal plasticity, red nucleus, deafferentation, middle cerebral artery occlusion, functional recovery, treatment delay
- MeSH terms
- Nogo Proteins, Animals, Antibodies, Monoclonal, Axons, Chronic Disease, Immunotherapy, Male, Myelin Proteins, Neuronal Plasticity, Time Factors, Recovery of Function, Rats, Long-Evans, Stroke, Rats
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