Glycolic acid protects neurons against ischemia in vitro and in two animal models of stroke

Chovsepian, A.; Berchtold, D.; Winek, K.; Mamrak, U.; Ramirez-Alvarez, I.; Dening, Y.; Weitbrecht, L.; Dames, C.; Aillery, M.; Fernandez-Sanz, C.; Dieterich, M.; Falkai, P.; Plesnila, N.; Meisel, A.; Pan-Montojo, F. J.

doi:10.1101/2020.11.24.396051

bioRxiv · 10.1101/2020.11.24.396051

Glycolic acid protects neurons against ischemia in vitro and in two animal models of stroke

Chovsepian, A.·Berchtold, D.·Winek, K.·Mamrak, U.·Ramirez-Alvarez, I.·Dening, Y.·Weitbrecht, L.·Dames, C.·Aillery, M.·Fernandez-Sanz, C.·Dieterich, M.·Falkai, P.·Plesnila, N.·Meisel, A.·Pan-Montojo, F. J.

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Abstract

Stroke is the second leading cause of death and disability worldwide. Current treatments, such as pharmacological thrombolysis or mechanical thrombectomy, re-open occluded arteries but do not protect against ischemia-induced damage that has already occurred before reperfusion or ischemia/reperfusion-induced neuronal damage. It has been shown that disrupting the conversion of glyoxal to glycolic acid (GA) results in a decreased tolerance to anhydrobiosis in C. elegans, dauer larva, while GA itself can rescue this phenotype. During the process of desiccation/rehydration, a metabolic stop/start similar to the one observed during ischemia/reperfusion occurs. In this study, we tested the protective effect of GA in different ischemia models, including commonly used stroke models in mice and swine. Our results show that GA, given during reperfusion, strongly protects against ischemic damage and improves the functional outcome. We provide evidence that GA exerts its effect by counteracting the glutamate-dependent increase in intracellular calcium during excitotoxicity. These results suggest that GA treatment has the potential to reduce the mortality and disability caused by stroke in patients.

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Chovsepian, A., Berchtold, D., Winek, K., Mamrak, U., Ramirez-Alvarez, I., Dening, Y., Weitbrecht, L., Dames, C., Aillery, M., Fernandez-Sanz, C., Dieterich, M., Falkai, P., Plesnila, N., Meisel, A., Pan-Montojo, F. J.. 2020-11-24. Glycolic acid protects neurons against ischemia in vitro and in two animal models of stroke. https://doi.org/10.1101/2020.11.24.396051

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