EFFECT OF NERVE GROWTH-FACTOR ON DELAYED NEURONAL DEATH AFTER CEREBRAL-ISCHEMIA

We investigated the protective action of nerve growth factor (NGF) on delayed neuronal death, and we also studied the involvement of the 200 kDa neurofilament (NF 200) cytoskeletal proteins. Wistar rats were divided into three groups: Group I, in which transient forebrain ischaemia was produced; Group II, ischaemic group which received intraventricular administration of artificial cerebrospinal fluid (CSF); and Group III, ischaemic group which received intraventricular administration of 2 mug of 2.5 S NGF. Forebrain ischaemia in these rats was produced by causing transient bilateral occlusion of the common carotid arteries and lowering the mean blood pressure to 50 mmHg for 8 minutes. On the 1 st and 7th day after ischaemia we histologically examined neuronal death in the hippocampal CA 1 sector. On the 7th day after ischaemia, mean cell death (degenerative cell number/total cell number) was 87 +/- 9% in group I (n = 7), 51 +/- 36% in group II (n = 7), and 14 +/- 16% in group III (n = 8) (p < 0.05 vs. group II). The concentration of NF200 in the hippocampal homogenate was measured by the Western blotting method on the 1st and 7th day after ischaemia. On the 1st day it was found to be 67 +/- 11% of that in the control group in group I (n = 6), 73 +/- 21% in group II (n = 6), and 84 +/- 7% in group III (n = 6) (p < 0.05 vs. group II). The concentration of NF 200 in all groups remained at the same level until the 7th day after ischaemia (each group, n = 6). These results suggest that 1) intraventricular NGF has a protective effect on delayed neuronal death, 2) these protective actions occur within one day after ischaemia, and 3) these effects may be mediated by the suppressed degradation and/or promoted restoration of neuronal cytoskeletal proteins.