NGF DELAYS RATHER THAN PREVENTS THE CHOLINERGIC TERMINAL DAMAGE AND DELAYED NEURONAL DEATH IN THE HIPPOCAMPUS AFTER ISCHEMIA

Cerebral ischemia induces damage of cholinergic terminals in the hippo campus, which preceded the delayed neuronal death (DND) of the CA1 pyr amidal cells. We investigated the effects of nerve growth factor (NGF) on the cholinergic terminal damage after ischemia. Continuous NGF inf usion (0.5 mu g/7 days) into the lateral ventricle before and after 5 min ischemia prevented a decrease in choline acetyltransferase (ChAT)- immunoreactivity and disturbance of acetylcholine (ACh) release on the 4th day after ischemia, but not on day 7, i.e., NGF infusion caused d elay in the progress of the cholinergic terminal damage. These finding s show that the cholinergic terminal damage may result from deficiency of endogenous NGF in an ischemic brain. In addition, we investigated whether NGF would prevent the DND after ischemia. NGF infusion also ca used delay in the progress of the DND until day 14. Our results sugges ted that the neuroprotective effect of NGF on the DND may be secondari ly yielded by maintenance of communication between cholinergic termina l and the target CA1 cell, and that prevention of cholinergic terminal damage may be useful for the treatment of cerebrovascular disease. (C ) 1998 Elsevier Science B.V.