(-)Clausenamide improves long-term potentiation impairment and attenuates apoptosis after transient middle cerebral artery occlusion in rats.
The effects of (-)clausenamide (clau) on long-term potentiation (LTP) and neuronal DNA damage were investigated in a rat model of middle cerebral artery (MCA) occlusion. Four days after reperfusion, electrophysiology records revealed reduced LTP in the ipsilateral dentate gyrus of ischemic rats, while treatment with clau (10 mg kg-1 p.o. once daily) improved LTP impairment. The fractional increase of population spike amplitude 20-50 min after tetanus was significantly larger in ischemic rats treated with clau than vehicle treated animals. Terminal deoxynucleotidyltransferase mediated dUTP end labeling (TUNEL) assay revealed occurrence of apoptosis in the ipsilateral striatum. The numbers of TUNEL-positive particles were significantly reduced after treatment with clau compared with vehicle group (78.8 +/- 17.9 versus 105.8 +/- 27.2). Mitochondrial rhodamine 123 accumulation showed that clau treatment (55.0 +/- 8.5) elevated numbers of rhodamine 123-positive particles in the ipsilateral striatum compared with vehicle group (40.4 +/- 7.5) These results demonstrate that clau can improve LTP impairment in the ipsilateral dentate gyrus and enhance cell survival in the striatum compared to the vehicle-treated rats four days following ischemic damage and its protective effect on mitochondria may partially underlie its action.
Tang
Kang
K
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. tangkang1969@hotmail.com
Zhang
Jun-Tian
JT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D004365:Drugs, Chinese Herbal; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D007769:Lactams / Q000494:pharmacology* / Q000627:therapeutic use*; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D004365:Drugs, Chinese Herbal; D007769:Lactams; D017705:Lignans; C053048:clausenamide