Angiogenesis is VEGF-independent in the aged striatum of male rats exposed to acute hypoxia.

Abstract

Brain hypoxia is involved in many diseases. The activation of angiogenesis is one of the major adaptive mechanisms to counteract the adverse effects of hypoxia. In a previous work, we have shown that the adult rat striatum promotes angiogenesis in response to hypoxia via upregulation of the most important proangiogenic factor, the vascular endothelial growth factor (VEGF). However, the effects of hypoxia on angiogenesis in the aged striatum remain unknown and constitute our aim. Here we show the upregulation of hypoxia-inducible factor-1α in the striatum of aged (24-25months old) Wistar rats exposed to acute hypoxia and analysed during a reoxygenation period ranging from 0h to 5days. While the mRNA expression of the proangiogenic factors VEGF, transforming growth factor-β1 (TGF-β1), and adrenomedullin dropped at 0h post-hypoxia compared to normoxic control, no changes were detected at the protein level, showing an impaired response of these proangiogenic factors to hypoxia in the aged striatum. However, the striatal blood vessel network increased at 24h of reoxygenation, suggesting that mechanisms independent from these proangiogenic factors may be involved in hypoxia-induced angiogenesis in the striatum of aged rats. A thorough understanding of the factors involved in the response to hypoxia is essential to guide the design of therapies for hypoxia-related diseases in the aged brain.