Niacin Treatment of Stroke Increases Synaptic Plasticity and Axon Growth in Rats

被引:72
作者
Cui, Xu [1 ]
Chopp, Michael [1 ,2 ]
Zacharek, Alex [1 ]
Roberts, Cynthia [1 ]
Buller, Benjamin [1 ,2 ]
Ion, Madalina [1 ]
Chen, Jieli [1 ]
机构
[1] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA
[2] Oakland Univ, Dept Phys, Rochester, MI USA
关键词
axon growth; HDL-cholesterol; niacin; plasticity; stroke; synaptic; BRAIN-INJURY; NEUROTROPHIC FACTOR; NEURITE OUTGROWTH; GENE-EXPRESSION; NERVOUS-SYSTEM; UP-REGULATION; SPINAL-CORD; NOGO-A; RECOVERY; RECEPTOR;
D O I
10.1161/STROKEAHA.110.589333
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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. (Stroke. 2010;41:2044-2049.)
引用
收藏
页码:2044 / 2049
页数:6
相关论文
共 32 条
  • [1] Motor cortical stimulation promotes synaptic plasticity and behavioral improvements following sensorimotor cortex lesions
    Adkins, DeAnna L.
    Hsu, J. Edward
    Jones, Theresa A.
    [J]. EXPERIMENTAL NEUROLOGY, 2008, 212 (01) : 14 - 28
  • [2] Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system
    Bibel, M
    Barde, YA
    [J]. GENES & DEVELOPMENT, 2000, 14 (23) : 2919 - 2937
  • [3] Age-related influence of the HDL receptor SR-BI on synaptic plasticity and cognition
    Chang, Eric H.
    Rigotti, Attilio
    Huerta, Patricio T.
    [J]. NEUROBIOLOGY OF AGING, 2009, 30 (03) : 407 - 419
  • [4] Niaspan increases angiogenesis and improves functional recovery after stroke
    Chen, Jieli
    Cui, Xu
    Zacharek, Alex
    Jiang, Hao
    Roberts, Cynthia
    Zhang, Chunling
    Lu, Mei
    Kapke, Alissa
    Feldkamp, Carolyn S.
    Chopp, Michael
    [J]. ANNALS OF NEUROLOGY, 2007, 62 (01) : 49 - 58
  • [5] Treatment of stroke with a synthetic liver X receptor agonist, TO901317, promotes synaptic plasticity and axonal regeneration in mice
    Chen, Jieli
    Zacharek, Alex
    Cui, Xu
    Shehadah, Amjad
    Jiang, Hao
    Roberts, Cynthia
    Lu, Mei
    Chopp, Michael
    [J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2010, 30 (01) : 102 - 109
  • [6] Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke
    Chen, JL
    Zhang, ZG
    Li, Y
    Wang, Y
    Wang, L
    Jiang, H
    Zhang, CL
    Lu, M
    Katakowski, M
    Feldkamp, CS
    Chopp, M
    [J]. ANNALS OF NEUROLOGY, 2003, 53 (06) : 743 - 751
  • [7] Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease - The ADMIT Study: A randomized trial
    Elam, MB
    Hunninghake, DB
    Davis, KB
    Garg, R
    Johnson, C
    Egan, D
    Kostis, JB
    Sheps, DS
    Brinton, EA
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2000, 284 (10): : 1263 - 1270
  • [8] Cortical sensory map rearrangement after spinal cord injury:: fMRI responses linked to Nogo signalling
    Endo, Toshiki
    Spenger, Christian
    Tominaga, Teiji
    Brene, Stefan
    Olson, Lars
    [J]. BRAIN, 2007, 130 : 2951 - 2961
  • [9] Bone marrow stromal cells increase astrocyte survival via upregulation of phosphoinositide 3-kinase/threonine protein kinase and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways and stimulate astrocyte trophic factor gene expression after anaerobic insult
    Gao, Q
    Li, Y
    Chopp, M
    [J]. NEUROSCIENCE, 2005, 136 (01) : 123 - 134
  • [10] Axonal regeneration, but not myelination, is partially dependent on local cholesterol reutilization in regenerating nerve
    Goodrum, JF
    Brown, JC
    Fowler, KA
    Bouldin, TW
    [J]. JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2000, 59 (11) : 1002 - 1010