Cyclooxygenase inhibition attenuates brain angiogenesis and independently decreases mouse survival under hypoxia.

ABSTRACT: Although cyclooxygenase (COX) role in cancer angiogenesis has been studied, little is known about its role in brain angioplasticity. In the present study, we chronically infused mice with ketorolac, a non-specific COX inhibitor that does not cross the blood-brain barrier (BBB), under normoxia or 50% isobaric hypoxia (10% O₂ by volume). Ketorolac increased mortality rate under hypoxia in a dose-dependent manner. Using in vivo multiphoton microscopy, we demonstrated that chronic COX inhibition completely attenuated brain angiogenic response to hypoxia. Alterations in a number of angiogenic factors that were reported to be COX-dependent in other models were assayed at 24-hr and 10-day hypoxia. Intriguingly, hypoxia-inducible factor 1 was unaffected under COX inhibition, and vascula

SUBMITTER: Seeger DR 

PROVIDER: S-EPMC8249483 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature