3.122 TISSUE PLASMINOGEN ACTIVATOR TREATMENT OF STROKE.pdf

TISSUE PLASMINOGEN ACTIVATOR TREATMENT OF STROKE IN TYPE-1 DIABETES RATS R. NINGa, M. CHOPPa,b, T. YANa, A. ZACHAREKa, C. ZHANGa, C. ROBERTSa, X. CUIa, M. LUc, and J. CHENa,* aDepartment of Neurology, Henry Ford Hospital, Detroit, MI 48202, United States bDepartment of Physics, Oakland University, Rochester, MI 48309, United States cDepartment of Biostatistics and Research Epidemiology, Detroit, MI 48202, United States Abstract Background and purpose—Diabetes mellitus (DM) is a major stroke risk factor and is associated with poor recovery compared with nondiabetic stroke patients. In the present study, we investigated the effects of tissue plasminogen activator (tPA) treatment of stroke in diabetic and non-diabetic rats. Methods—Type-1 diabetes (T1DM) was induced by injection of streptozotocin. Non-T1DM and T1DM rats were subjected to embolic middle cerebral artery occlusion (MCAo) and treated with or without tPA 2 h after MCAo. Functional outcomes and immunostaining for advanced glycation endproducts receptor (RAGE), matrix metalloproteinase-9 (MMP-9) and toll-like receptor 4 (TLR4) and Western blotting were performed. Results—tPA treatment of WT-MCAo rats significantly improved the functional outcome and reduced the lesion volume compared with non-treatment WT-MCAo rats (p 0.05). There was no significant difference between treatment with or without tPA in the WT-MCAo group in brain hemorrhage, BBB leakage and expression of inflammatory mediators, RAGE, MMP-9 and TLR4. However, tPA treatment in T1DM-MCAo rats (T1DM-MCAo + tPA) significantly enlarged brain hemorrhage, augmented BBB leakage, and failed to decrease lesion volume and improve functional outcome after stroke compared to T1DM-MCAo control. tPA treatment also significantly increased the expression of RAGE, MMP-9 and TLR4 in the ischemic brain in T1DM-MCAo rats compared with T1DM-MCAo control rats (p 0.05). Brain hemorrhage was significantly correlated with functional deficit and RAGE and TLR4 expression,