TEMPORAL PROFILES OF NERVE GROWTH-FACTOR BETA-SUBUNIT LEVEL IN RAT-BRAIN REGIONS AFTER TRANSIENT ISCHEMIA

To determine the role of nerve growth factor (NGF) in ischemic brain damage, we measured the temporal and regional changes in the level of NGF in the hippocampal subfields, the cerebral cortex, the striatum, and the septum at 1, 2, 7, and 30 days after transient forebrain ischemia using a highly sensitive sandwich-type enzyme immunoassay system for the beta-subunit of mouse 7S NGF (beta-NGF). We also analyzed glial fibrillary acidic protein immunoreactivity in the hippocampus to ascertain the contribution of reactive astrocytes to NGF production after an ischemic insult. In the CA1 subfield of the hippocampus. the level of beta-NGF decreased slightly 2 days after ischemia (not significant), at which time CA1 pyramidal cell loss began to occur, and increased by 40% 30 days after ischemia (p < 0.05). A marked increase in glial fibrillary acidic protein-positive astrocytes in the CA1 subfield 2-30 days after ischemia suggests that the reactive astrocytes participated in a gradual increase in the level of beta-NGF after recirculation. The level of beta-NGF in the dentate gyrus decreased transiently 2 days (p < 0.05) and 7 days (p < 0.01) after ischemia, followed by recovery to the level of control animals 30 days after ischemia. The level of beta-NGF in the septum gradually decreased 7 days (-27%, p < 0.05) and 30 days (-43%, p < 0.01) after ischemia. The levels of beta-NGF in the cerebral cortex and striatum remained unaltered throughout the observation period. These results suggest that the alteration of NGF content occurs not only in the CA1 subfield. where pyramidal cells are depleted, but also in areas with minimal histological damage. Septal decrease in NGF may reflect the reduction of retrograde NGF transport from hippocampus to septal cholinergic neurons.