title: Niaspan reduces high-mobility group box 1/receptor for advanced glycation endproducts after stroke in type-1 diabetic rats.
abstract: OBJECTIVE
  High-mobility group box 1 (HMGB1), an active receptor for advanced glycation endproducts (RAGE), functions as a potent proinflammatory cytokine-like factor that contributes to the pathogenesis of vasculature. Diabetes mellitus (DM) is associated with accelerated development of both microvascular and macrovascular disease and increases the risk of ischemic stroke. Using a model of streptozotocin-induced type-1 diabetes (T1DM) in rats, we investigated the changes in HMGB and RAGE and tested the effects of Niaspan, a slow release form of niacin, on the expression of pro-inflammatory proteins in rats after stroke.
  
  
  METHODS
  T1DM rats were subjected to transient middle cerebral artery occlusion (MCAo) and treated without or with Niaspan (40 mg/kg) daily for 14 days after MCAo. Non-streptozotocin rats (WT) were also subjected to MCAo. Immunostaining for inflammatory mediators including HMGB1, RAGE, matrix metalloproteinase-9 (MMP-9) and toll-like receptor 4 (TLR4) immunostaining (n=8/group) and Western blotting (n=4/group) were performed.
  
  
  RESULTS
  Compared to WT-MCAo rats, T1DM-MCAo rats showed an increased expression of HMGB1 (0.82±0.07 vs. 1.81±0.98, P<0.05), RAGE (1.31±0.22 vs. 3.77±0.72, P<0.05), MMP-9 (0.74±0.08 vs. 1.61±0.09, P<0.05) and TLR4 (2.85±0.22 vs. 6.72±0.44, P<0.05) after stroke. Niaspan treatment significantly attenuated the expression of HMGB1 (1.80±0.98 vs. 1.31±0.01, P<0.05), RAGE (3.77±0.71 vs. 1.78±0.45, P<0.05), MMP-9 (1.61±0.09 vs. 0.97±0.07, P<0.05) and TLR4 (6.72±0.44 vs. 2.28±0.43, P<0.05) in the ischemic brain in T1DM-MCAo rats.
  
  
  CONCLUSIONS
  T1DM increases HMGB1/RAGE, TLR4 and MMP-9 expression after stroke. Niaspan treatment of stroke in T1DM rats inhibits HMGB1/RAGE, TLR4 and MMP-9 expression which may contribute to the reduced inflammatory response after stroke in T1DM rats.
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, Jiangsu Province, China.
authors.forename: X
authors.initials: X
authors.lastname: Ye
authors.forename: M
authors.initials: M
authors.lastname: Chopp
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: A
authors.initials: A
authors.lastname: Zacharek
authors.forename: X
authors.initials: X
authors.lastname: Cui
authors.forename: T
authors.initials: T
authors.lastname: Yan
authors.forename: C
authors.initials: C
authors.lastname: Roberts
authors.forename: J
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism*; D024002:HMGB Proteins / Q000378:metabolism*; D008297:Male; D009525:Niacin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D020521:Stroke / Q000150:complications / Q000378:metabolism*
chemical_list: D024002:HMGB Proteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009525:Niacin