title: Niaspan attenuates the adverse effects of bone marrow stromal cell treatment of stroke in type one diabetic rats.
abstract: OBJECTIVE
  Our previous studies have found that bone-marrow-stromal cells (BMSC) therapy improves functional recovery after stroke in non-diabetic rats while increases brain hemorrhage and induces arteriosclerosis-like changes in type-one-diabetic (T1DM) rats. Niaspan treatment of stroke increases vascular stabilization, decreases brain hemorrhage and blood-brain-barrier (BBB) leakage in T1DM rats. We therefore tested the hypothesis that combination therapy of BMSC with Niaspan attenuates the side effects of BMSC monotherapy in T1DM rats.
  
  
  METHODS
  T1DM-rats induced by streptozotocin were subjected to 2 hours of middle-cerebral-artery occlusion (MCAo) and treated with: 1) PBS; 2) BMSC (5×10(6)); 3) Niaspan (40 mg/kg) daily for 14 days; 4) BMSC (5×10(6)) +Niaspan (40 mg/kg, daily for 14 days) combination starting at 24 hours after MCAo. All rats were monitored for 14 days.
  
  
  RESULTS
  Combination BMSC+Niaspan treatment of T1DM-MCAo rats did not increase brain hemorrhage, and significantly decreased BBB leakage and vascular arteriosclerosis-like changes as well as decreased Angiogenin, matrix metalloproteinase 9 (MMP9) and ED1 expression in ischemic brain and internal-carotid-artery compared to non-treatment control and BMSC monotherapy animals.
  
  
  CONCLUSIONS
  Combination therapy using BMSC with Niaspan decreases BBB leakage and cerebral arteriosclerosis-like changes. These beneficial effects may be attributed to the decreased expression of Angiogenin, MMP9 and ED1.
authors.affiliation: Neurology, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Tianjin, China ; Neurology, Henry Ford Hospital, Detroit, Michigan, United States of America.
authors.forename: Tao
authors.initials: T
authors.lastname: Yan
authors.forename: Xinchun
authors.initials: X
authors.lastname: Ye
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
authors.forename: Alex
authors.initials: A
authors.lastname: Zacharek
authors.forename: Ruizhuo
authors.initials: R
authors.lastname: Ning
authors.forename: Poornima
authors.initials: P
authors.lastname: Venkat
authors.forename: Cynthia
authors.initials: C
authors.lastname: Roberts
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Jieli
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D004195:Disease Models, Animal; D053331:Ectodysplasins / Q000378:metabolism; D002537:Intracranial Arteriosclerosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D059630:Mesenchymal Stem Cells; D009525:Niacin / Q000008:administration & dosage*; D010539:Permeability; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D020521:Stroke / Q000150:complications* / Q000473:pathology / Q000628:therapy*; D000071939:Stroke Rehabilitation
chemical_list: D053331:Ectodysplasins; D009525:Niacin; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; D020780:Matrix Metalloproteinase 9