Effects of the AT1 Receptor Antagonist L-158,809 on Microglia and Neurogenesis after Fractionated Whole-Brain Irradiation

Abstract Cognitive dysfunction develops in approximately 50% of patients who receive fractionated whole-brain irradiation and survive 6 months or more. The mechanisms underlying these deficits are unknown. A recent study demonstrated that treatment with the angiotensin II type 1 receptor antagonist (AT1RA) L-158,809 before, during and after fractionated whole-brain irradiation prevents or ameliorates radiation-induced cognitive deficits in adult rats. Given that (1) AT1RAs may function as anti-inflammatory drugs, (2) inflammation is thought to contribute to radiation injury, and (3) radiation-induced inflammation alters progenitor cell populations, we tested whether the cognitive benefits of L-158,809 treatment were associated with amelioration of the sustained neuroinflammation and changes in neurogenesis that are induced by fractionated whole-brain irradiation. In rats examined 28 and 54 weeks after irradiation, L-158,809 treatment did not alter the effects of radiation on the number and activation of m...