Functional recovery and neuroanatomical plasticity following middle cerebral artery occlusion and IN-1 antibody treatment in the adult rat
Abstract
Stroke is a prevalent and devastating disorder, and no treatment is currently available to restore lost neuronal function after stroke occurs. One unique therapy that may improve functional recovery after stroke is blockade of the neurite inhibitory protein Nogo‐A with the monoclonal antibody IN‐1, through enhancement of neuroanatomical plasticity from uninjured areas of the central nervous system. In the present study, we combined IN‐1 treatment with an ischemic lesion (permanent middle cerebral artery occlusion) to determine the effect of Nogo‐A neutralization on cortical plasticity and functional recovery. We report here that, following ischemic stroke and treatment with IN‐1, adult rats demonstrated functional recovery on a forelimb‐reaching task and new cortico‐efferent projections from the opposite, unlesioned hemisphere. These results support the efficacy of Nogo‐A blockade as a treatment for ischemic stroke and implicate plasticity from the unlesioned hemisphere as a mechanism for recovery.
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Homologous fibres from the contralesional motor cortex grow across the midline to reach denervated neurons in target structures of the lesioned pyramidal tract.
“Instead, homologous fibres originating from the contralesional motor cortex grow out across the midline to reach denervated neurons in target structures of the lesioned pyramidal tract (figure 1).10–12,15,17,19,24”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [10]
Treatments promoting neurological recovery by remodelling brain tissue can be instituted during the stroke recovery phase, unlike neuroprotection which requires acute intervention.
“By contrast with neuroprotection, which requires an acute intervention, treatments promoting neurological recovery by remodelling of brain tissue can be instituted during the stroke recovery phase.10–15”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [10]
This lesion-remote plasticity involves midline crossing of fibres from contralesional to ipsilesional hemisphere at the red nucleus and re-entry into contralesional hemicord at cervical spinal cord.
“This lesion-remote plasticity involves the midline crossing of fibres from the contralesional to the ipsilesional hemisphere at the level of the red nucleus10,17,19,24 and the re-entry of fibres into the contralesional hemicord at the level of the cervical spinal cord (figure 1).11,12,15”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [10]
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- Authors
- Papadopoulos, C. M., Tsai, S., Alsbiei, T., O'Brien, T. E., Schwab, M. E., & Kartje, G. L.
- Affiliations
- Loyola University Medical Center (US)
- Edward Hines, Jr. VA Hospital (US)
- University of Zurich (CH)
- Corresponding author
- Kartje, Gwendolyn L.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2002-02-19
- Volume
- 51
- Issue
- 4
- Pages
- 433-441
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2052886216
- Cited by
- 249
- References
- 65
- Citations by year
- 2026: 2 · 2025: 4 · 2023: 4 · 2022: 2 · 2021: 5 · 2020: 8 · 2019: 5 · 2018: 10 · 2017: 7 · 2016: 6 · 2015: 7 · 2014: 12 · 2013: 20 · 2012: 14
- FWCI
- 19.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- ischemic stroke, Nogo-A, middle cerebral artery occlusion, functional recovery, cortical plasticity, forelimb reaching, axon regeneration
- MeSH terms
- Nogo Proteins, Age Factors, Animals, Antibodies, Monoclonal, Feeding Behavior, Male, Myelin Proteins, Neuronal Plasticity, Somatosensory Cortex, Recovery of Function, Infarction, Middle Cerebral Artery, Rats, Long-Evans, Stroke, Rats
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