HIF‐1alpha and COX‐2 expression and mouse brain capillary remodeling during adaptation to hypoxia and re‐oxygenation after prolonged moderate hypoxia

Abstract

Normal brain function is delicately sensitive to continuous and controlled oxygen delivery. One of the ways that the brain maintains its optimal continuous supply of oxygen and nutrients is through brain angiogenic adaptational changes. Hence, the objective of this study was to determine the relative time course of the capillary regression during re‐oxygenation after chronic hypoxic exposure, and expression of some of the signaling factors involved in the process. Four month old male C57BL/6 mice were kept in a hypobaric chamber at 290 torr (0.4 ATM) for 21 days and allowed to recover at normoxia for up to 21 days. The mice were either decapitated or perfused in situ and brain samples collected were either lysated for Western blot analysis or paraffin embedded for immunohistochemistry. Hypoxia inducible factor 1alpha (HIF‐1á) accumulation in hypoxia was observed to be diminished during re‐oxygenation; however, Cyclooxygenase‐2 (COX‐2) expression was elevated during hypoxia as well as re‐oxygenation. Significantly increased capillary density at the end of the 3rd week of hypoxia regressed toward normoxic level as the duration of re‐oxygenation was prolonged. In conclusion, increased COX‐2 expression during hypoxia where angiogenesis occurs and re‐oxygenation, when micro‐vessels regress indicates the involvement of this enzyme in wide range of brain angioplasticity.Grant Funding Source : NS38632