The effects of (-)clausenamide on functional recovery in transient focal cerebral ischemia.
The effects of (-)clausenamide (clau) on spatial cognitive functions and hippocampal long-term potentiation (LTP) after transient focal cerebral ischemia in rats were investigated. Four weeks after middle cerebral artery occlusion, Morris water maze tasks demonstrated that 2 h of transient forebrain ischemia resulted in a significant decrease in spatial discrimination performance. The escape latency at 4 and 5 days of acquisition trial was lower in the ischemic rats than in sham-operated rats (33.8+/-6.7 sec and 26.8+/-5 sec versus 12.2+/-4.0 sec and 10.4+/-3.6 sec), chronic treatment with clau (10 mg kg(-1) p.o. once daily) significantly improved the impairment (12.4+/-4.1 sec and 15.2+/-3.1 sec). After Morris water maze, the changes in population spike (PS) amplitude were recorded as an index of LTP in the perforant path-dentate gyrus synapses. There was no difference in PS amplitude between the sham-operated and vehicle-treated animals, whereas the fractional increase of PS 20-50 min after tetanus was significantly larger in clau-treated group. Histopathological analysis revealed that clau could protect against neuron loss in the regions of cortex and striatum. In conclusion, these data indicate a beneficial effect of clau for synaptic plasticity and cognitive function impaired by transient focal cerebral ischemia.
Tang
Kang
K
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing. tangk@imm.ac.cn
Zhang
Jun-Tian
JT
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007769:Lactams / Q000494:pharmacology*; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016896:Treatment Outcome
D004365:Drugs, Chinese Herbal; D007769:Lactams; D017705:Lignans; C053048:clausenamide