NEAMINE INDUCES NEUROPROTECTION AFTER ACUTE ISCHEMIC STROKE IN TYPE ONE DIABETIC RATS

Introduction: 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 (60 mg/kg, ip), and T1DM rats were subjected to embolic middle cerebral artery occlusion (MCAo). Neamine (10 mg/kg ip) was administered at 2, 24 and 48 h 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 (NF kappa B) 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. Conclusion: 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. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.