Abstract WMP118: Neuroprotective Effects of IGF1 on Brain Microvascular Endothelial Cells Under Ischemic Conditions Can Be Replicated by Antagomirs to MicroRNA(Mir-92b) and Mir33a

Background: Insulin like growth factor (IGF1) treatment to middle aged female rats post stroke reduces infarct volume, and this is preceded by reduced permeability of the blood brain barrier (BBB) at 4h post stroke. Analysis of ischemic tissue at 4h showed that IGF1 treatment significantly reduced expression of 8 miRNA. To determine if these miRNA are mechanistically linked to barrier function, we tested the impact of these miRNA on barrier function using human brain microvascular endothelial cells (hBMECs) under ischemic conditions. Specifically, we mimicked the actions of IGF1 by using antagomirs to miR-29c, miR-33a and miR-92b. Methods: hBMECs were grown to confluence on collagen-coated dishes (5% CO2, 95% air) and exposed to acute oxygen-glucose deprivation (6h OGD, 1% O2 % and 5 % CO2) in the presence of IGF1 or vehicle. In addition, cultures were also treated with IGF1+JB-1 (IGFR antagonist), IGF1+ LY294002 (Akt inhibitor) and rapamycin (mTOR inhibitor), to establish IGF1 mediated pathways on barrie...