BACKGROUND AND PURPOSE: Poststroke hyperglycemia is associated with resistance to tissue plasminogen activator (tPA) reperfusion, higher risk of intracerebral hemorrhage, and worse neurological outcomes. In this study, we asked whether minocycline combined with intravenous tPA may ameliorate inflammation and brain injury after focal embolic stroke in type 1 diabetic rats. METHODS: Type 1 diabetic rats were subjected to a focal embolic stroke. Three treatment groups were used: (1) saline at 1.5 hours after stroke; (2) tPA alone at 1.5 hours after stroke; (3) combined minocycline (intravenously) at 1 hour plus tPA at 1.5 hours, and second treatment of minocycline (intraperitoneally) at 12 hours after stroke. Acute brain tissue damages were assessed at 24 hours after stroke. Inflammatory biomarkers interleukin-1β and matrix metalloproteinases 2 and 9 were examined in plasma. Neutrophil infiltration, microglia activation, matrix metalloproteinase activation, and degradation of the tight junction protein claudin-5 were examined in the brain. RESULTS: Compared with saline or tPA alone treatments, minocycline plus tPA combination therapy significantly reduced brain infarction, intracerebral hemorrhage, and hemispheric swelling at 24 hours after stroke. The combination also significantly suppressed the elevated plasma levels of matrix metalloproteinase-9 and interleukin-1β up to 24 hours after stroke. At 16 hours after stroke, neutrophil infiltration, microglia activation, matrix metalloproteinase-9, and tight junction protein claudin-5 degradation in the peri-infarct brain tissues were also significantly attenuated by the combination therapy. CONCLUSIONS: Combination therapy with minocycline plus tPA may be beneficial in ameliorating inflammation and reducing infarction, brain swelling, and hemorrhage after ischemic stroke with diabetes mellitus/hyperglycemia.
BACKGROUND AND PURPOSE:Poststroke hyperglycemia is associated with resistance to tissue plasminogen activator (tPA) reperfusion, higher risk of intracerebral hemorrhage, and worse neurological outcomes. In this study, we asked whether minocycline combined with intravenous tPA may ameliorate inflammation and brain injury after focal embolic stroke in type 1 diabeticrats. METHODS: Type 1 diabeticrats were subjected to a focal embolic stroke. Three treatment groups were used: (1) saline at 1.5 hours after stroke; (2) tPA alone at 1.5 hours after stroke; (3) combined minocycline (intravenously) at 1 hour plus tPA at 1.5 hours, and second treatment of minocycline (intraperitoneally) at 12 hours after stroke. Acute brain tissue damages were assessed at 24 hours after stroke. Inflammatory biomarkers interleukin-1β and matrix metalloproteinases 2 and 9 were examined in plasma. Neutrophil infiltration, microglia activation, matrix metalloproteinase activation, and degradation of the tight junction protein claudin-5 were examined in the brain. RESULTS: Compared with saline or tPA alone treatments, minocycline plus tPA combination therapy significantly reduced brain infarction, intracerebral hemorrhage, and hemispheric swelling at 24 hours after stroke. The combination also significantly suppressed the elevated plasma levels of matrix metalloproteinase-9 and interleukin-1β up to 24 hours after stroke. At 16 hours after stroke, neutrophil infiltration, microglia activation, matrix metalloproteinase-9, and tight junction protein claudin-5 degradation in the peri-infarct brain tissues were also significantly attenuated by the combination therapy. CONCLUSIONS: Combination therapy with minocycline plus tPA may be beneficial in ameliorating inflammation and reducing infarction, brain swelling, and hemorrhage after ischemic stroke with diabetes mellitus/hyperglycemia.
Authors: Susan C Fagan; Jennifer L Waller; Fenwick T Nichols; David J Edwards; L Creed Pettigrew; Wayne M Clark; Christiana E Hall; Jeffrey A Switzer; Adviye Ergul; David C Hess Journal: Stroke Date: 2010-08-12 Impact factor: 7.914
Authors: Leslie Ritter; Lisa Davidson; Melissa Henry; Grace Davis-Gorman; Helena Morrison; Jennifer B Frye; Zoe Cohen; Sierra Chandler; Paul McDonagh; Janet L Funk Journal: Microcirculation Date: 2011-10 Impact factor: 2.628
Authors: V Wee Yong; Jennifer Wells; Fabrizio Giuliani; Steven Casha; Christopher Power; Luanne M Metz Journal: Lancet Neurol Date: 2004-12 Impact factor: 44.182
Authors: Yoshihiro Murata; Anna Rosell; Robert H Scannevin; Kenneth J Rhodes; Xiaoying Wang; Eng H Lo Journal: Stroke Date: 2008-10-16 Impact factor: 7.914
Authors: Eloy Cuadrado; Laura Ortega; Mar Hernández-Guillamon; Anna Penalba; Israel Fernández-Cadenas; Anna Rosell; Joan Montaner Journal: J Leukoc Biol Date: 2008-04-07 Impact factor: 4.962
Authors: Alexandre Y Poppe; Sumit R Majumdar; Thomas Jeerakathil; William Ghali; Alastair M Buchan; Michael D Hill Journal: Diabetes Care Date: 2009-01-08 Impact factor: 17.152
Authors: Konark Malhotra; Jason J Chang; Arjun Khunger; David Blacker; Jeffrey A Switzer; Nitin Goyal; Adrian V Hernandez; Vinay Pasupuleti; Andrei V Alexandrov; Georgios Tsivgoulis Journal: J Neurol Date: 2018-06-14 Impact factor: 4.849