Intraparenchymal injections of glutamate analogues into the diencephalon near the supraoptic (SON) and paraventricular nucleus (PVN) of the hypothalamus selectively spare magnocellular neuroendocrine cells. In this study we investigated for the first time the susceptibility of this neuronal population to ischemia. Temporary focal ischemia was produced using a three-vessel occlusion method involving unilateral middle cerebral artery and bilateral common carotid artery occlusion (MCAO/CCAO). Most of the 3-h ischemic period was maintained without anesthesia and reversed by microclip removal of the contralateral common carotid artery occlusion. In one subset of rats transcardial perfusion with India ink was used to estimate the degree of ischemia produced during MCAO/CCAO in the SON, lateral magnocellular nucleus of the PVN (PVL), caudoputamen (CP), and frontoparietal cortex (COR). Computer-assisted densitometry measurements of ink density indicated significant reductions in ink penetration in the territory of the occluded MCA within the SON (46%), PVL (45%), CP (53%), and COR (76%). In contrast, neither sham-operated rats nor rats subjected to occlusion of the MCA alone showed differences in ink optical densities between the sides ipsilateral and contralateral to MCAO. The other subset of rats were perfused 48-72 h after recovery and brain sections were examined for neurodegenerative changes. While the incidences of cerebral and caudoputamen infarction after MCAO/CCAO were 98.4 and 52%, respectively, the histological features of the SON or PVL in ischemic rats were similar to those of control rats. Reduced susceptibility of magnocellular neuroendocrine cells to ischemia may be due to a number of mechanisms including neuronal resilience, neuroprotection by glia and vascular/perivascular cells, and access to perivascular cerebrospinal fluid. (C) 2002 Elsevier Science (USA).