title: l-3-n-Butylphthalide improves cognitive impairment induced by chronic cerebral hypoperfusion in rats.
abstract: 3-n-Butylphthalide (NBP) may be beneficial for the treatment of ischemic stroke with multiple actions on different pathophysiological processes. In the present study, we investigated the effect of NBP isomers on learning and memory impairment induced by chronic cerebral hypoperfusion in rats. Male Wistar rats were orally administered 10 and 30 mg/kg l-, d-, or dl-NBP daily for 23 days after bilateral permanent occlusion of the common carotid arteries. Rats receiving 10 mg/kg l-NBP performed significantly better in tests for spatial learning and memory, and they had attenuated cerebral pathology, including neuronal damage, white matter rarefaction, and glial activation compared with controls. Furthermore, 10 mg/kg l-NBP-treated rats had significantly higher choline acetyltransferase activity, decreased cortical lipid peroxide, and reduced hippocampal superoxide dismutase activity, compared with vehicle controls. However, d- and dl-NBP did not show significant beneficial effects. The present findings demonstrate that the beneficial effects of l-NBP on hypoperfusion-induced cognitive deficits may be due to preventing neuropathological alterations, inhibiting oxidative damage and increasing acetylcholine synthesis. Our results strongly suggest that l-NBP has therapeutic potential for the treatment of dementia caused by decreased cerebral blood flow.
authors: Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, China.
authors: Ying
authors: Y
authors: Peng
authors: Shaofeng
authors: S
authors: Xu
authors: Guiquan
authors: G
authors: Chen
authors: Ling
authors: L
authors: Wang
authors: Yipu
authors: Y
authors: Feng
authors: Xiaoliang
authors: X
authors: Wang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001572:Benzofurans / Q000494:pharmacology / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000150:complications*; D017536:Carotid Artery, Common / Q000601:surgery; D002374:Catalase / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D003337:Corpus Callosum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007859:Learning Disabilities / Q000188:drug therapy / Q000209:etiology; D008026:Ligation; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014795:Visual Pathways / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D001572:Benzofurans; D018696:Neuroprotective Agents; C027125:3-n-butylphthalide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase