title: Neamine induces neuroprotection after acute ischemic stroke in type one diabetic rats.
abstract: BACKGROUND
  Angiogenin is a member of the ribonuclease superfamily and promotes degradation of the basement membrane and the extracellular matrix. After stroke in type one diabetes (T1DM) rats, Angiogenin is significantly increased and the Angiogenin is inversely correlated with functional outcome. Neamine, an aminoglycoside antibiotic, blocks nuclear translocation of Angiogenin, thereby abolishing the biological activity of Angiogenin. In this study, we therefore investigated the effect and underlying protective mechanisms of Neamine treatment of stroke in T1DM.
  
  
  METHODS
  T1DM was induced in male Wistar rats by streptozotocin (60mg/kg, ip), and T1DM rats were subjected to embolic middle cerebral artery occlusion (MCAo). Neamine (10mg/kg ip) was administered at 2, 24 and 48h after the induction of embolic MCAo. A battery of functional outcome tests was performed. Blood-brain barrier (BBB) leakage, and lesion volume were evaluated and immunostaining, and Western blot were performed.
  
  
  RESULTS
  Neamine treatment of stroke in T1DM rats significantly decreased BBB leakage and lesion volume as well as improved functional outcome compared to T1DM-control. Neamine also significantly decreased apoptosis and cleaved caspase-3 in the ischemic brain. Using immunostaining, we found that Neamine treatment significantly decreased nuclear Angiogenin, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) activity, advanced glycation endproducts receptor (RAGE) number, the positive area of toll-like receptor 4 (TLR4) and increased Angeopoietin-1 expression compared to T1DM-MCAo control rats. Western blot results are consistent with the immunostaining.
  
  
  CONCLUSIONS
  Neamine treatment of stroke is neuroprotective in T1DM rats. Inhibition of neuroinflammatory factor expression and decrease of BBB leakage may contribute to Neamine-induced neuroprotective effects after stroke in T1DM rats.
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: R
authors.initials: R
authors.lastname: Ning
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI, USA; Department of Physics, Oakland University, Rochester, MI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Chopp
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: A
authors.initials: A
authors.lastname: Zacharek
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI, USA; Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300060, China.
authors.forename: T
authors.initials: T
authors.lastname: Yan
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: C
authors.initials: C
authors.lastname: Roberts
authors.affiliation: Biostatistics and Research Epidemiology, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI, USA; Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300060, China. Electronic address: jieli@neuro.hfh.edu.
authors.forename: J
authors.initials: J
authors.lastname: Chen
mesh_terms: D042682:Angiopoietins / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D001831:Body Temperature / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D005119:Extravasation of Diagnostic and Therapeutic Materials; D005601:Framycetin / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D012720:Severity of Illness Index; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D042682:Angiopoietins; D053148:Caspase 3; D005601:Framycetin; D018696:Neuroprotective Agents; D017346:Protein Serine-Threonine Kinases; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D051197:Toll-Like Receptor 4; D000097782:NF-kappaB-Inducing Kinase; C488396:neamine
keywords: Ang1; Angiogenin; BBB; BP; BT; DM; ECA; ECM; IBZ; ICA; MCAo; NFκB; Neamine; PBS; RAGE; T1DM; TLR4; TUNEL; WT; advanced glycation end products receptor; angiopoietin-1; blood pressure; blood–brain barrier; body temperature; diabetes mellitus; external carotid artery; extracellular matrix; internal carotid artery; ischemic border area; mNSS; middle cerebral artery occlusion; modified neurological severity score; neuroprotection; nuclear factor kappa-light-chain-enhancer of activated B cells; phosphate-buffered saline; stroke; terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; toll-like receptor 4; type one diabetes; wild type