NERVE GROWTH-FACTOR PROTECTS THE NEONATAL BRAIN AGAINST HYPOXIC-ISCHEMIC INJURY

Nerve growth factor (NGF) has been shown to protect specific neurons t hat express its signaling receptor, trkA, from a variety of insults. T here are some data, in particular in the developing brain, indicating that NGF has neuroprotective actions that extend beyond cells expressi ng trkA. In this study, rye asked whether NGF would protect against br ain injury in a neonatal model of hypoxia-ischemia. Postnatal day (PD) 7 rat pups received a right carotid ligation and were then exposed to hypoxic conditions. Prior to carotid ligation and 48 hours later, pup s received an intracerebroventricular injection of NGF or denatured NG F dissolved in vehicle or vehicle alone. Brains were then assessed at PD21. In vehicle- and denatured NGF-treated animals, there was signifi cant damage (30-40% volume loss) to both the striatum and cortex ipsil ateral to the carotid ligation. In contrast, little damage (10% volume loss) was observed in most NGF-treated animals. NGF injection studies revealed that NGF stimulated tyrosine phosphorylation of trkA in mult iple brain regions. These results show that NGF appears globally neuro protective to the developing brain in a neonatal model of hypoxia-isch emia and that there may be novel mechanisms in vivo through which NGF exerts its protective actions.