AIMTo investigate the causative role of nitric oxide synthase (NOS) and nitric oxide (NO) in neurotoxicity of beta-amyloid (Abeta) and the pathogenesis of Alzheimer's disease (AD).

METHODSUsing behavioral and neuropathological methods, we observed the effects of Abeta(1-40) injection into hippocampi on rats learning and memory in Y maze and on the neuropathology in hippocampi. The intervention by intraperitoneal administration of aminoguanidine (AG), a selective inducible NOS (iNOS) inhibitor, and 7-nitroindazole (7-NI), a selective neuronal NOS (nNOS) inhibitor, in the neurotoxicity of Abeta(1-40) was studied then.

RESULTSThe capability of acquisition and retrieval in Y maze and local neurons in hippocampus of the rats were impaired significantly after Abeta(1-40) injection. Intraperitoneal administration of AG, but not 7-NI, could prevent the damages caused by Abeta(1-40) injection above-mentioned.

CONCLUSIONiNOS/NO participates in the mechanisms of Abeta-induced neurotoxicity and may play an important role in the pathogenesis of AD.

Alzheimer Disease ; metabolism ; pathology ; Amyloid beta-Peptides ; metabolism ; toxicity ; Animals ; Guanidines ; pharmacology ; Indazoles ; pharmacology ; Male ; Maze Learning ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; antagonists & inhibitors ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Sprague-Dawley

Objective To assess the efficacy, safety, and tolerability of verapamil as prophylactic therapy for patients withcluster headache, and compare its efficacy with that of prednisone.Methods Prospectively, according to the order of visit, a total of 45 patients with episodic cluster headache or chronic cluster headache were divided into verapamil treatment group (n=23, the odd) and prednisone treatment group (n=22, the even). The seizure frequency, and times of and dosage of using acesodyne were observed in the 2 groups 1 week before treatment, 1 and 2 week after treatment.Results Mean frequency of headache occurrence decreased from 8.78 to 2.52 and 1.35 times,respectively, in the first and second week of treatment in the verapamil group (P=0.000) and from 8.09 to 2.95 and 1.64 times, respectively, at the corresponding time in the prednisone group (P=0.000). Mean abortive agent consumption decreased from 8.09 to 1.65 and 0.48 pills, respectively, in the verapamil group (P=0.000) and from 7.77 to 2.59 and 1.36 pills, respectively, in the prednisone group (P=0.000) in the first and second week of treatment; no significant differences existed in the mean frequency of headache and abortive agent consumption between the 2 groups at the same time point (P＞0.05). The side effects of verapamil were mild, including dizziness, constipation and bradycardia and those ofprednisone were insomnia, increased appetite combined with weight gain and discomfort of abdomen. Conclusion Both verapamil and prednisone prophylaxis therapy for episodic and chronic cluster headache yield significant reduction in headache frequency and abortive agent consumption; choices can be made according to different situations.