Stress hyperglycemia exacerbates inflammatory brain injury after stroke

Won, S. J.; Zhang, Y.; Butler, N. J.; Kim, K.; Mocanu, E.; Nzoutchoum, O. T.; Lakkaraju, R.; Davis, J.; Ghosh, S.; Swanson, R. A.

doi:10.1101/2024.05.14.594195

bioRxiv · 10.1101/2024.05.14.594195

Stress hyperglycemia exacerbates inflammatory brain injury after stroke

Won, S. J.·Zhang, Y.·Butler, N. J.·Kim, K.·Mocanu, E.·Nzoutchoum, O. T.·Lakkaraju, R.·Davis, J.·Ghosh, S.·Swanson, R. A.

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Abstract

Post-stroke hyperglycemia occurs in 30% - 60% of ischemic stroke patients as part of the systemic stress response, but neither clinical evidence nor pre-clinical studies indicate whether post-stroke hyperglycemia affects stroke outcome. Here we investigated this issue using a mouse model of permanent ischemia. Mice were maintained either normoglycemic or hyperglycemic during the interval of 17 - 48 hours after ischemia onset. Post-stroke hyperglycemia was found to increase infarct volume, blood-brain barrier disruption, and hemorrhage formation, and to impair motor recovery. Post-stroke hyperglycemia also increased superoxide formation by peri-infarct microglia/macrophages. In contrast, post-stroke hyperglycemia did not increase superoxide formation or exacerbate motor impairment in p47phox-/- mice, which cannot form an active superoxide-producing NADPH oxidase-2 complex. These results suggest that hyperglycemia occurring hours-to-days after ischemia can increase oxidative stress in peri-infarct tissues by fueling NADPH oxidase activity in reactive microglia/macrophages, and by this mechanism contribute to worsened functional outcome.

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Won, S. J., Zhang, Y., Butler, N. J., Kim, K., Mocanu, E., Nzoutchoum, O. T., Lakkaraju, R., Davis, J., Ghosh, S., Swanson, R. A.. 2024-05-14. Stress hyperglycemia exacerbates inflammatory brain injury after stroke. https://doi.org/10.1101/2024.05.14.594195

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