Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia
Abstract
Progenitor cells in the subventricular zone of the lateral ventricle and in the dentate gyrus of the hippocampus can proliferate throughout the life of the animal. To examine the proliferation and fate of progenitor cells in the subventricular zone and dentate gyrus after focal cerebral ischemia, we measured the temporal and spatial profiles of proliferation of cells and the phenotypic fate of proliferating cells in ischemic brain in a model of embolic middle cerebral artery occlusion in the adult rat. Proliferating cells were labeled by injection of bromodeoxyuridine (BrdU) in a pulse or a cumulative protocol. To determine the temporal profile of proliferating cells, ischemic rats were injected with BrdU every 4 h for 12 h on the day preceding death. Rats were killed 2-14 days after ischemia. We observed significant increases in numbers of proliferating cells in the ipsilateral cortex and subventricular zone 2-14 days with a peak at 7 days after ischemia compared with the control group. To maximize labeling of proliferating cells, a single daily injection of BrdU was administered over a 14-day period starting the day after ischemia. Rats were killed either 2 h or 28 days after the last injection of BrdU. A significant increase in numbers of BrdU immunoreactive cells in the subventricular zone was coincident with a significant increase in numbers of BrdU immunoreactive cells in the olfactory bulb 14 days after ischemia and numbers of BrdU immunoreactive cells did not significantly increase in the dentate gyrus. However, 28 days after the last labeling, the number of BrdU labeled cells decreased by 90% compared with number at 14 days. Clusters of BrdU labeled cells were present in the cortex distal to the infarction. Numerous cells immunostained for the polysialylated form of the neuronal cell adhesion molecule were detected in the ipsilateral subventricular zone. Only 6% of BrdU labeled cells exhibited glial fibrillary acidic protein immunoreactivity in the cortex and subcortex and no BrdU labeled cells expressed neuronal protein markers (neural nuclear protein and microtubule associated protein-2). From these data we suggest that focal cerebral ischemia induces transient and regional specific increases in cell proliferation in the ipsilateral hemisphere and that proliferating progenitor cells may exist in the adult cortex.
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Neurogenesis is sustained in the subventricular zone and dentate gyrus subgranular layer, which host neural precursor cells even in adulthood.
“Neurogenesis is sustained in the germinal niches in the subventricular zone of the lateral ventricle and the subgranular layer of the dentate gyrus, which host neural precursor cells even during adulthood.34,35”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [34]
Neurogenesis is stimulated in response to stroke and is substantially amplified by therapeutic interventions that promote functional recovery.
“Neurogenesis is stimulated in response to stroke and is substantially amplified by therapeutic interventions that promote functional recovery.33–36”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [34]
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- Authors
- Zhang, R. L., Zhang, Z. G., Zhang, L., & Chopp, M.
- Affiliations
- Henry Ford Health (US)
- Corresponding author
- Chopp, M
- ORCID
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2001-07
- Volume
- 105
- Issue
- 1
- Pages
- 33-41
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2026990513
- Cited by
- 576
- References
- 31
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 13 · 2023: 5 · 2022: 10 · 2021: 12 · 2020: 19 · 2019: 8 · 2018: 16 · 2017: 13 · 2016: 24 · 2015: 21 · 2014: 25 · 2013: 31 · 2012: 24
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ns035504-03)
- National Institute of Neurological Disorders and Stroke (P01NS23393, R01-NS35504, P01NS023393)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Keywords
- subventricular zone, adult neurogenesis, progenitor cells, cell proliferation, dentate gyrus, middle cerebral artery occlusion, olfactory bulb, glial fibrillary acidic protein, cortical infarction
- MeSH terms
- Age Factors, Animals, Antimetabolites, Bromodeoxyuridine, Cell Differentiation, Cell Division, Cerebral Cortex, Brain Ischemia, Glial Fibrillary Acidic Protein, Immunohistochemistry, Male, Microtubule-Associated Proteins, Nerve Regeneration, Neurons, Sialic Acids, Stem Cells, Rats, Wistar, Neural Cell Adhesion Molecules, Recovery of Function, Lateral Ventricles, Neural Cell Adhesion Molecule L1, Rats
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