Grant: Operating Grant

At birth some babies experience a condition called "asphyxia", i.e., their brain and other organs do not receive enough blood and/or oxygen. This is a life-threatening condition that often causes permanent damage, including cerebral palsy, mental retardation, and loss of vision. Our recent work indicates that the loss of vision following birth asphyxia may arise from damage to the brain, but also to the eyes. Currently, no treatment exists to repair these brain and eye damages in newborns. In the adult brain, new blood vessels are growing near the brain damage area to try to repair these damages and drugs promoting these repair processes (e.g., sildenafil [Viagra®]) do successfully reduce the size of the brain damage. Sildenafil is already safely used to treat babies with pulmonary hypertension, but its effects on brain and eyes have never been studied. Our recent work did show that new blood vessels are also growing near the brain damage area in the newborn brain, and that sildenafil appears to repair brain and eyes damage following asphyxia. We hypothesize that (A) birth asphyxia has a profound impact on eyes and vision, that (B) new growing vessels are involved in the repair processes of brain and eye damage following birth asphyxia and that (C) sildenafil may significantly enhance these repair processes. We will study human term asphyxiated babies treated with hypothermia, and determine the impact of asphyxia on the eye and vision. We also will use a rat model of term neonatal asphyxia, to: (1) assess the impact of asphyxia on the eye and vision, (2) characterize the mechanism of new growing vessels in the brain and eye following asphyxia, and (3) evaluate the efficacy of sildenafil in repairing these brain and eye damage. This project will allow us to study a novel mechanism of injury to both the brain and the eyes following birth asphyxia and determine if sildenafil is an efficient treatment to repair brain and eye damage in these babies.