Abstract WP225: Rapid Complement Activation Induced By Acute Hyperglycemia Worsens Ischemic Stroke Outcome

• Published in: Stroke (1970) 2023-02, Vol.54 (Suppl_1), p.AWP225-AWP225
• Main Authors: Chen, Hansen, Chiang, Terrance, Kim, Anika, Tomlinson, Stephen, Bliss, Tonya, Cheng, Michelle Y, Steinberg, Gary
• Format: Article
• Language: English
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/str.54.suppl_1.WP225

BackgroundAcute hyperglycemia, which occurs in over 40% of ischemic stroke patients regardless of pre-existing diabetes, increases brain edema, hemorrhagic transformation (HT) and worsens stroke outcome. Understanding the mechanisms of hyperglycemia-exacerbated stroke injury will be vital for developing novel treatments. Here we identify systemic complement activation as a novel contributor to hyperglycemic-exacerbated damage in rodent stroke. MethodMale C57/BL6 mice (10-11 weeks) were subjected to middle cerebral artery occlusion (MCAO) for 30 min, followed by reperfusion to mimic ischemic stroke. Acute hyperglycemia was induced by glucose injection 10 min before MCAO. To assess the effect of hyperglycemia on stroke outcomes, mice were sacrificed at 4.5 and 24 hr post-stroke to analyze brain edema, blood-brain barrier (BBB) leakage, and HT; or allowed to survive 14 days to examine mortality rate, neurological deficit, and motor-sensory dysfunction using the horizontal rotating beam test. Complement activation was evaluated at 1, 2, 4.5 hr post-stroke. To inhibit C3 activation, the targeted complement inhibitor CR2-Crry fusion protein, or PBS control, was injected via femoral vein 15 min after reperfusion. ResultHyperglycemia worsens stroke outcomes in our mouse model, with rapid increased BBB leakage (p