Effects of nicotine on blood flow and delayed neuronal death following intermittent transient ischemia in rat hippocampus.
A cholinergic neural vasodilative response in the cerebral cortex and hippocampus, independent of metabolic vasodilation, was recently demonstrated by activating the nicotinic acetylcholine receptors (nAChRs) via activation of cholinergic neurons originating in the nucleus basalis of Meynert and septal complex in the basal forebrain and projecting to the cortex and hippocampus (see reviews by Sato A and Sato Y: Neurosci Res 14: 242--274, 1992; Sato A and Sato Y: Alzheimer Dis Assoc Disord 9: 28--38, 1995). In the present study, we aimed to examine whether an increase in regional blood flow in the hippocampus (Hpc-BF) following stimulation of the nAChRs by i.v. injection of nicotine could improve the delayed death of the hippocampal neurons following transient ischemia in rats. Hpc-BF was measured by using a laser Doppler flowmeter. During intermittent (every 2 min) transient occlusion for a total of 6 min of bilateral carotid arteries besides permanent ligation of bilateral vertebral arteries, Hpc-BF decreased to about 16% of the preocclusion level, and 5 or 7 d later, after the occlusion, delayed neuronal death occurred in approximately 70% of the CA1 hippocampal neurons. Hpc-BF was increased dose-dependently by injection of nicotine (30--100 microg/kg, i.v.), independent of mean arterial pressure. Nicotine (30--100 microg/kg) administered 5 min before occlusion slightly but significantly attenuated the occlusion-induced decrease in Hpc-BF. The delayed death of the CA1 hippocampal neurons occurring after transient occlusion was attenuated by pretreatment with nicotine (30--100 microg/kg) to approximately 50% of the total neurons. The results indicate that nAChR stimulation-induced increases in Hpc-BF can protect against ischemia-induced delayed death of hippocampal neurons.
Kagitani
F
F
Department of the Autonomic Nervous System, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015 Japan.
Uchida
S
S
Hotta
H
H
Sato
A
A
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D006624:Hippocampus / Q000098:blood supply* / Q000503:physiopathology; D007275:Injections, Intravenous; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D009538:Nicotine