title: Combination treatment of experimental stroke with Niaspan and Simvastatin, reduces axonal damage and improves functional outcome.
abstract: In this study we examined the effect of combination treatment of experimental stroke with Niaspan, a prolonged-release formulation of Niacin (vitamin B3), and Simvastatin, a cholesterol-lowering drug, on functional outcome, axonal damage, axonal density and the of Iba-1 immunoreactive microglia expression in the ischemic brain of rats. Adult male rats were subjected to 2 h middle cerebral artery occlusion (MCAo) and treated with or without Niaspan alone, Simvastatin alone and combination Niaspan and Simvastatin starting 24 h after MCAo and daily for 14 days. Neurological functional tests were performed. Axonal damage and density were evaluated by Amyloid Precursor Protein (APP) and Bielschowsky silver, respectively. Nogo66 Receptor (NgR) expression and immunoreactive microglia (Iba-1) were also measured in the ischemic brain. Niaspan and Simvastatin monotherapy and combination treatment significantly promote functional outcome after stroke (p<0.05) compared to MCAo control animals. Combination treatment with Niaspan and Simvastatin induces additive but not synergetic effects when compared to Niaspan or Simvastatin monotherapy groups. Combination treatment significantly decreased APP expression and increased Bielschowsky silver expression. NGR and Iba-1 expression were significantly decreased in the ischemic brain. These data suggest that treatment of experimental stroke with combination of Niaspan and Simvastatin significantly improves functional outcome, reduces axonal damage and increases axonal density. Decreased expression of the NGR and reduced activated microglia may contribute to functional recovery after stroke.
authors.affiliation: Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI, 48202, USA.
authors.forename: Amjad
authors.initials: A
authors.lastname: Shehadah
authors.forename: Jieli
authors.initials: J
authors.lastname: Chen
authors.forename: Xu
authors.initials: X
authors.lastname: Cui
authors.forename: Cynthia
authors.initials: C
authors.lastname: Roberts
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D058851:GPI-Linked Proteins; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008840:Microfilament Proteins; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009185:Myelin Proteins; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009525:Niacin / Q000627:therapeutic use*; D000070816:Nogo Receptor 1; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide / Q000378:metabolism; D019821:Simvastatin / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: C100745:Aif1 protein, rat; D016564:Amyloid beta-Protein Precursor; D002135:Calcium-Binding Proteins; D003692:Delayed-Action Preparations; D058851:GPI-Linked Proteins; D008840:Microfilament Proteins; D009185:Myelin Proteins; D018696:Neuroprotective Agents; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C486581:Rtn4r protein, rat; D009525:Niacin; D019821:Simvastatin
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