Effect of nerve growth factor on delayed neuronal death and microtubule-associated protein 2 after transient cerebral ischaemia in the rat.

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia

PubMedID: 18638743

Tanaka K, Tsukahara T, Kaku Y, Hashimoto N, Yonekawa Y, Ogata N, Kimura T, Taniguchi T. Effect of nerve growth factor on delayed neuronal death and microtubule-associated protein 2 after transient cerebral ischaemia in the rat. J Clin Neurosci. 1994;1(2):125-30.
The protective action of nerve growth factor (NGF) on delayed neuronal death (DND) after transient cerebral ischaemia and on the associated decrease in microtubule-associated protein 2 (MAP2) has been investigated. Transient forebrain ischaemia was induced for different periods (2 min, 5 min, and 8 min) in male Wistar rats by transient bilateral occlusion of the common carotid arteries and by lowering the systemic blood pressure to 50 mmHg. Histological evaluation of neuronal cell death and immunoblot analysis of MAP2 were made on the first and the seventh days after ischaemia. The mean cell death on the seventh day after ischaemia was 2.0%+/-1.8% in the 2-min group (n=6), 41%+/-19% in the 5-min group (n=6), and 75%+/-20% in the 8-min group (n=6). The concentration of MAP2 in the hippocampal homogenate 24 hours after ischaemia decreased to 82%+/-9% of the control value in the 2-min group (n=6), to 65%+/-8% in the 5-min group (n=6), and to 58%+/-4% in the 8-min group (n=6), and it remained constant at these levels through the seventh day after ischaemia. The protective action of NGF against DND was studied by administering 2 mug of 2.5S NGF (NGF-treated group, n=6) or artificial cerebrospinal fluid (CSF-treated group, n=6) through an osmotic pump implanted in the lateral ventricles 48 hours before the onset of ischaemia. The mean cell death on the seventh day after ischaemia was 42%+/-31% in the CSF-treated group, and 11%+/-15% in the NGF-treated group. The concentration of MAP2 in the hippocampal homogenate on the first day after ischaemia was 75%+/-9% in the CSF-treated group, and 82%+/-6% in the NGF-treated group, and it remained at about the same levels up to the 7th day after ischaemia. These results suggest that, 1: degradation of MAP2 precedes DND, 2: the severity of the preceding decrease of MAP2 correlated well with the severity of the DND, 3: intraventricular NGF has a protective effect against DND, and 4: the effect of NGF brain injury may be mediated by the modulation of MAP2 metabolism.