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Growth-associated gene expression after stroke: evidence for a growth-promoting region in peri-infarct cortex
Abstract
Stroke induces axonal sprouting in peri-infarct cortex. A set of growth-associated genes important in axonal sprouting in peripheral nervous system regeneration and cortical development has recently been defined. The expression profiles of these growth-associated genes were defined during the post-stroke axonal sprouting response using a model of stroke in barrel field cortex. Stroke induces sequential waves of neuronal growth-promoting genes during the sprouting response: an early expression peak (SPRR1), a mid expression peak (p21, Ta1 tubulin, L1, MARCKS), a late peak (SCG10, SCLIP), and an early/sustained pattern (GAP43, CAP23, c-jun). These expression peaks correspond to specific time points in the sprouting response. The expression of the growth-inhibiting chondroitin sulfate proteoglycans aggrecan, brevican, versican, and phosphacan are induced late in the sprouting process; except neurocan, which is increased during the peak of the growth-promoting gene expression. The developmentally associated growth inhibitors ephrin-A5, ephB1, semaphorin IIIa, and neuropilin 1 are also induced in the early phases of the sprouting response. At the cellular level, chondroitin sulfate proteoglycans, in the form of peri-neuronal nets, are reduced in the region of axonal sprouting, during the peak of growth-promoting gene expression. These results identify a unique profile of growth-promoting gene expression in adult cortex after stroke, the inhibitory molecules that are present during the sprouting response, and a region in which growth-promoting genes are increased, growth-inhibitory proteins are diminished and axonal sprouting occurs. This region may be a growth-promoting zone after stroke.
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“In response to focal cerebral ischaemia, these proteoglycans are downregulated in areas exhibiting axonal growth over a period of 2–3 weeks after stroke.64”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [64]
In the citing paper
“Despite the robust evidence for specific time windows in which neuronal plasticity and angiogenesis are most active,64,66,67 neurorestorative treatments were still successful in animals once brain remodelling was induced months after the stroke.18,20”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [64]
In the citing paper
“focal cortical stroke in rats contributes to upregulation of a number of CSPG-encoding genes particularly near the infarct and glial scar.”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Carmichael et al., 2005
In the citing paper
“as well as versican and brevican, both of which peaked by day 28 (Carmichael et al., 2005).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Carmichael et al., 2005
In the citing paper
“RT-PCR analysis of the affected tissue indicated upregulation of neurocan, which peaked on the third day following middle cerebral artery occlusion”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Carmichael et al., 2005
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Metadata
- Authors
- Carmichael, S. T., Archibeque, I., Luke, L., Nolan, T., Momiy, J., & Li, S.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Carmichael, S. Thomas
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 193
- Issue
- 2
- Pages
- 291-311
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W1997912239
- Cited by
- 421
- References
- 89
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 14 · 2023: 12 · 2022: 18 · 2021: 15 · 2020: 21 · 2019: 21 · 2018: 23 · 2017: 24 · 2016: 29 · 2015: 20 · 2014: 26 · 2013: 35 · 2012: 25
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS045729)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- stroke, axonal sprouting, peri-infarct cortex, chondroitin sulfate proteoglycans, growth inhibitors, ephrin-A5, neuropilin-1, EphB1, GAP-43, c-Jun, neuroplasticity
- MeSH terms
- Animals, Cerebral Cortex, Chondroitin Sulfates, Disease Models, Animal, Gene Expression Regulation, Immunohistochemistry, Male, Nerve Growth Factors, Nerve Tissue Proteins, Chondroitin Sulfate Proteoglycans, Proteoglycans, Rats, Inbred F344, RNA, Messenger, Time Factors, Gene Expression, Extracellular Matrix Proteins, In Situ Hybridization, Reverse Transcriptase Polymerase Chain Reaction, Brain Infarction, Stroke, Lectins, C-Type, Rats, Aggrecans, Versicans, Receptor-Like Protein Tyrosine Phosphatases, Class 5
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