Metabotropic glutamate receptors and brain ischemia: differential effects on phospoinositide turnover in young and aged rats.

Neuronal damage and phosphoinositide hydrolysis stimulated by neurotransmitter receptor agonists in cerebral cortex of 3- and 24-month Fischer 344 rats, following an episode of brain ischemia, were compared. Transient global ischemia was induced by occlusion of common carotid arteries for 15 minutes in conditions of moderate hypoxia. Seven days after, histological examination of cerebral cortex showed cell loss, neurons with nuclear pyknosis, cytoplasmatic degeneration, and glial proliferation. Ischemic lesions appeared moderate to severe in young rats and intermediate in all the aged animals. In young rats inositol phosphates accumulation stimulated by excitatory amino acids (ACPD, ibotenate and quisqualate), but not by norepinephrine or carbachol, was enhanced significantly with respect to sham-operated animals. No potentiation at all was observed in aged rats. This finding suggests that the events leading to the increased metabotropic response in th e post-ischemia period is impaired by the ageing process.