title: Niacin treatment of stroke increases synaptic plasticity and axon growth in rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, Mich 48202, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Cui
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
authors.forename: Alex
authors.initials: A
authors.lastname: Zacharek
authors.forename: Cynthia
authors.initials: C
authors.lastname: Roberts
authors.forename: Benjamin
authors.initials: B
authors.lastname: Buller
authors.forename: Madalina
authors.initials: M
authors.lastname: Ion
authors.forename: Jieli
authors.initials: J
authors.lastname: Chen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000187:drug effects*; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002478:Cells, Cultured; D058851:GPI-Linked Proteins; D007150:Immunohistochemistry; D008297:Male; D009185:Myelin Proteins; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009525:Niacin / Q000494:pharmacology / Q000627:therapeutic use*; D000070816:Nogo Receptor 1; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000378:metabolism; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C486581:Rtn4r protein, rat; D016708:Synaptophysin; D009525:Niacin; D020813:Receptor, trkB