Cognitive recovery in the aged rat after stroke and anti-Nogo-A immunotherapy
Open accessAbstract
We have previously shown that immunotherapy directed against the protein Nogo-A leads to recovery on a skilled forelimb reaching task in rats after sensorimotor cortex stroke, which correlated with axonal and dendritic plasticity. Here we investigated anti-Nogo-A immunotherapy as an intervention to improve performance on a spatial memory task in aged rats after stroke, and whether cognitive recovery was correlated with structural plasticity. Aged rats underwent a unilateral distal permanent middle cerebral artery occlusion and one week later were treated with an anti-Nogo-A or control antibody. Nine weeks post-stroke, treated rats and normal aged rats were tested on the Morris water maze task. Following testing rats were sacrificed and brains processed for the Golgi-Cox method. Hippocampal CA3 and CA1 pyramidal and dentate gyrus granule cells were examined for dendritic length and number of branch segments, and CA3 and CA1 pyramidal cells were examined for spine density and morphology. Anti-Nogo-A immunotherapy given one week following stroke in aged rats improved performance on the reference memory portion of the Morris water maze task. However, this improved performance was not correlated with structural changes in the hippocampal neurons examined. Our finding of improved performance on the Morris water maze in aged rats after stroke and treatment with anti-Nogo-A immunotherapy demonstrates the promising therapeutic potential for anti-Nogo-A immunotherapy to treat cognitive deficits after stroke. The identification of sites of axonal and dendritic plasticity in the aged brain after stroke and treatment with anti-Nogo-A immunotherapy is still under investigation.
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In old rats (24 months), anti-NogoA antibodies did not affect dendritic and synaptic plasticity of hippocampal CA3 and CA1 pyramidal and dentate gyrus granule cells, yet spatial memory improved.
“Although neurological recovery was successful, dendritic and synaptic plasticity of hippocampal CA3 and CA1 pyramidal and dentate gyrus granule cells was not influenced by anti-NogoA antibodies in old rats (24 months of age), yet improvements in spatial memory were reported.77”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [77]
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Self-citationPreclinical Evidence of Nogo-A Inhibition in Stroke Recovery: A Scoping Review
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Self-citationExperience-dependent expression of Nogo-A and Nogo receptor in the developing rat visual cortex.
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Effects of neuronal Nogo-A on properties of excitatory synapses of the sensorimotor cortex
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- Authors
- Gillani, R. L., Tsai, S.-Y., Wallace, D. G., O’Brien, T. E., Arhebamen, E., Tole, M., Schwab, M. E., & Kartje, G. L.
- Affiliations
- Loyola University Chicago (US)
- Edward Hines, Jr. VA Hospital (US)
- Northern Illinois University (US)
- University of Zurich (CH)
- Corresponding author
- Gillani, Rebecca L.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 208
- Issue
- 2
- Pages
- 415-424
- ISSN
- 0166-4328 (ISSN-L)
- PMC
- PMC2831114
- OpenAlex
- W2130007083
- Cited by
- 59
- References
- 48
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 9 · 2012: 8
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- Novartis
- University of Chicago
- Loyola University Chicago
- U.S. Public Health Service (40960)
- Novartis Pharma
- National Institute of Neurological Disorders and Stroke (F30NS060560, 30NS060560, R01NS040960, R56NS040960)
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- Nogo-A, stroke, cognitive recovery, aged rats, spatial memory, reference memory, hippocampus, dendritic plasticity, axonal plasticity, dendritic spine density, dendritic length, middle cerebral artery occlusion, neuroprotection
- MeSH terms
- Nogo Proteins, Aging, Analysis of Variance, Animals, Antibodies, Brain, Cognition Disorders, Dendrites, Disease Models, Animal, Hippocampus, Immunotherapy, Injections, Intra-Articular, Functional Laterality, Motor Activity, Myelin Proteins, Neurons, Silver Staining, Maze Learning, Recovery of Function, Infarction, Middle Cerebral Artery, Rats
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