Niacin treatment of stroke increases synaptic plasticity and axon growth in rats
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Background and Purpose— Niacin is the most effective medication in current clinical use for increasing high-density lipoprotein cholesterol. We tested the hypothesis that niacin treatment of stroke promotes synaptic plasticity and axon growth in the ischemic brain. Methods— Male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion and treated with or without Niaspan (a prolonged-release formulation of niacin, 40 mg/kg) daily for 14 days starting 24 hours after middle cerebral artery occlusion. The expression of synaptophysin, Nogo receptor, Bielschowsky silver, brain-derived neurotrophic factor, and its receptor tropomyosin-related kinase B were measured by immunohistostaining and Western blot, respectively, in the ischemic brain. Complementing in vivo studies, primary cultured neurons were used to test the effect of niacin and high-density lipoprotein on neurite outgrowth and brain-derived neurotrophic factor/tropomyosin-related kinase B expression. Results— Niaspan treatment of stroke significantly increased synaptophysin, Bielschowsky silver, brain-derived neurotrophic factor/tropomyosin-related kinase B expression, and decreased Nogo receptor expression in the ischemic brain compared with middle cerebral artery occlusion control animals ( P <0.05, n=8/group). Niacin and high-density lipoprotein treatment significantly increased neurite outgrowth and brain-derived neurotrophic factor/tropomyosin-related kinase B expression in primary cultured neurons. Tropomyosin-related kinase B inhibitor attenuated niacin-induced neurite outgrowth ( P <0.05, n=6/group). Conclusions— Niacin treatment of stroke promotes synaptic plasticity and axon growth, which is mediated, at least partially, by the brain-derived neurotrophic factor/tropomyosin-related kinase B pathways.
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In rodents, survival of ischaemic pyramidal tract axons can be improved by pharmacological and cell-based treatments.
“In rodents, the survival of ischaemic pyramidal tract axons can be improved by pharmacological and cell-based treatments.26–28”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [28]
After focal cerebral ischaemia in rats, vitamin B3 increased HDL concentrations, enhanced white matter remodelling in peri-infarct tissue, increased BDNF and TrkB levels, and downregulated Nogo-receptor levels.
“After focal cerebral ischaemia in rats, vitamin B3 was used to increase high-density lipoprotein concentrations, which enhanced white matter remodelling in the peri-infarct tissue, increased BDNF and TrkB levels, and down regulated Nogo-receptor levels.88”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [88]
Given the high prevalence of hypercholesterolaemia in stroke patients, blood lipids might be a suitable target for neurorestorative therapies.
“In view of the high prevalence of hypercholesterolaemia in stroke patients, blood lipids might be a suitable target for neurorestorative therapies.”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [88]
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Mechanisms of Plasticity Remodeling and Recovery
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Self-citationThe role of B vitamins in preventing the progression of glaucomatous optic neuropathy
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Self-citationAn Enhanced Green Fluorescence Protein-based Assay for Studying Neurite Outgrowth in Primary Neurons
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Mechanisms of Plasticity, Remodeling and Recovery
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Self-citationRestorative Therapies after Stroke: Drugs, Devices, and Robotics
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Encapsulation-Free Local Delivery of BDNF Enhances Recovery in Stroke-Injured Rats
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- Authors
- Cui, X., Chopp, M., Zacharek, A., Roberts, C., Buller, B., Ion, M., & Chen, J.
- Affiliations
- Henry Ford Health (US)
- Venue
- Stroke
- Published
- 2010-09
- Volume
- 41
- Issue
- 9
- Pages
- 2044-2049
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- PMC
- PMC2932778
- OpenAlex
- W2160479657
- Cited by
- 74
- References
- 33
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 8 · 2018: 5 · 2017: 2 · 2016: 4 · 2015: 5 · 2014: 10 · 2013: 4 · 2012: 8
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Stroke (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG031811)
- National Institute of Neurological Disorders and Stroke (P01NS23393, P01NS023393, R41NS064708)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- nicotinic acid, Niaspan, ischemic brain, synaptic plasticity, axon growth, neurite outgrowth, brain-derived neurotrophic factor, Nogo receptor, high-density lipoprotein, middle cerebral artery occlusion, synaptophysin, neuroprotection
- MeSH terms
- Nogo Receptor 1, Analysis of Variance, Animals, Axons, Cells, Cultured, Immunohistochemistry, Male, Myelin Proteins, Neuronal Plasticity, Neurons, Niacin, Receptors, Cell Surface, Blotting, Western, Synaptophysin, Rats, Wistar, Receptors, Peptide, Brain-Derived Neurotrophic Factor, Reverse Transcriptase Polymerase Chain Reaction, Stroke, Receptor, trkB, Rats, GPI-Linked Proteins
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