Bone marrow stromal cells enhance inter- and intracortical axonal connections after ischemic stroke in adult rats
Open accessAbstract
We investigated axonal plasticity in the bilateral motor cortices in rats after unilateral stroke and bone marrow stromal cell (BMSC) treatment. Rats were subjected to permanent right middle cerebral artery occlusion followed by intravenous administration of phosphate-buffered saline or BMSCs 1 day later. Adhesive-removal test and modified neurologic severity score were performed weekly to monitor limb functional deficit and recovery. Anterograde tracing with biotinylated dextran amine injected into the right motor cortex was used to assess axonal sprouting in the contralateral motor cortex and ipsilateral rostral forelimb area. Animals were killed 28 days after stroke. Progressive functional recovery was significantly enhanced by BMSCs. Compared with normal animals, axonal density in both contralateral motor cortex and ipsilateral rostral forelimb area significantly increased after stroke. Bone marrow stromal cells markedly enhanced such interhemispheric and intracortical connections. However, labeled transcallosal axons in the corpus callosum were not altered with either stroke or treatment. Both interhemispheric and intracortical axonal sprouting were significantly and highly correlated with behavioral outcome after stroke. This study suggests that, after stroke, cortical neurons surviving in the peri-infarct motor cortex undergo axonal sprouting to restore connections between different cerebral areas. Bone marrow stromal cells enhance axonal plasticity, which may underlie neurologic functional improvement.
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Remodelling of transcallosal projections connecting the two motor cortices occurs after stroke.
“In addition to the sprouting of pyramidal tract fibres, remodelling of transcallosal projections connecting the two motor cortices occurs.14,25”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [25]
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- Authors
- Liu, Z., Li, Y., Zhang, Z. G., Cui, X., Cui, Y., Lu, M., Savant-Bhonsale, S., & Chopp, M.
- Affiliations
- Henry Ford Health (US)
- Department of Biostatistics and Research Epidemiology, Henry Ford Hospital, Detroit, Michigan, USA
- Theradigm Inc., Baltimore, Maryland, USA
- Corresponding author
- Chopp, Michael
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2010-02-03
- Volume
- 30
- Issue
- 7
- Pages
- 1288-1295
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC2896436
- OpenAlex
- W1975029375
- Cited by
- 111
- References
- 40
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 2 · 2020: 6 · 2019: 8 · 2018: 6 · 2017: 3 · 2016: 10 · 2015: 10 · 2014: 6 · 2013: 13 · 2012: 17
- FWCI
- 14.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (P01NS42345, R01NS066041, P01NS042345)
- Topics
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- mesenchymal stem cells, ischemic stroke, axonal plasticity, axonal sprouting, interhemispheric connections, intracortical connections, motor cortex, middle cerebral artery occlusion, functional recovery, corpus callosum, peri-infarct cortex, cell therapy
- MeSH terms
- Animals, Axons, Behavior, Animal, Bone Marrow Cells, Brain, Humans, Male, Nerve Regeneration, Neuronal Plasticity, Random Allocation, Stromal Cells, Rats, Wistar, Recovery of Function, Infarction, Middle Cerebral Artery, Stroke, Rats
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