Selective immunotoxin-induced cholinergic deafferentation alters blood flow distribution in the cerebral cortex

Adult rats received intracerebroventricular (i.c.v.) administration of either phosphate buffer (PBS) or 192 Igc-saporin (Toxin), 3.6 mu g rat(-1), a cholinergic immunotoxin. Six to eight weeks later, the animals received a continuous intravenous (i.v.) infusion of either physostigmine (4.2 mu g kg(-1) min(-1)) or saline, followed by measurement of cerebral cortical blood flow (CBF) with the autoradiographic Iodo-C-14-antipyrine methodology in four groups of animals: Toxin i.c.v. + saline i.v. (n = 9), Toxin i.c.v. + physostigmine i.v. (n = 6), PBS i.c.v. + saline i.v. (n = 6) and PBS i.c.v. + physostigmine i.v. (n = 6). Choline acetyltransferase activity (ChAT) was assessed with Fonnum's method in samples of cortical tissue adjacent to the sites of CBF measurement. ChAT decreased in all regions of the Toxin groups when compared to PBS (% decrease: hippocampus = 93%, neocortex = 80-84%, entorhinal-piriform cortex = 42%, amygdala = 28%). CBF decreased globally in Toxin + SAL, most severely in posterior parietal and temporal regions (24-40% decrease from PBS + saline). Physostigmine enhanced CBF predominantly in these same areas both in PBS and Toxin animals although to a lesser extent in the latter. Our results demonstrate the importance of cholinergic mechanisms in the control of CBF. The similarity between the topography of CBF decrease following administration of the immunotoxin to that observed in Alzheimer's disease suggests that the CBF pattern observed in this disease may be the result of cholinergic deafferentation. (C) 1999 Elsevier Science B.V. All rights reserved.