Abstract T P248: Leukemia Inhibitory Factor Induced-Akt Activation Protects Neurons from Ischemic Damage by Increasing Superoxide Dismutase Activity and Expression

Objective: To determine the molecular mechanisms by which leukemia inhibitory factor (LIF) protects neurons during permanent middle cerebral artery occlusion (MCAO). Hypothesis: LIF protects neurons from ischemic oxidative injury through Akt-mediated increases in superoxide dismutase 3 (SOD3) expression and total SOD activity. Methods: Male Sprague-Dawley rats injected with vehicle (PBS) or LIF (125 μg/kg) were euthanized 24, 48, and 72 h post-MCAO or sham surgery for assessment of SOD activity and SOD3 expression. Rat cortical neurons were subjected to 24 h oxygen glucose deprivation or normoxia following treatment with vehicle , 50, 200, or 1000 ng/mL LIF (n=3 per group). In a third experiment, neurons were treated with vehicle, 50 ng/mL LIF,10 μM Akt inhibitor, or 50 ng/mL LIF+10 μM Akt inhibitor (n=3 per group) prior to oxygen glucose deprivation. Lactate dehydrogenase levels in media were measured to assess neuronal death. We used immunocytochemistry to assess expression of SOD3, phospho-Akt (Ser473)...