Neuroprotective effects of dauricine against apoptosis induced by transient focal cerebral ischaemia in rats via a mitochondrial pathway.
1. Previous experimental studies have shown that dauricine can protect the brain against ischaemic damage, but the underlying mechanisms remain unknown. In the present study, we examined whether dauricine inhibits neuronal apoptosis in the penumbra in a rat model of transient focal cerebral ischaemia. 2. Male Wistar rats underwent a 90 min temporary occlusion of the middle cerebral artery. Dauricine (21, 42 and 84 mg/kg) was administered by intragastric gavage twice a day for 3 days before ischaemia. Rats were killed and brain samples were collected 24 h after ischaemia. Histopathological outcome was evaluated by haematoxylin-eosin staining. Apoptotic changes were evaluated by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) for DNA fragmentation. The mitochondrial pathway was explored using immunohistochemistry for cytochrome c release, caspase 9 and caspase 3 activation, as well as by reverse transcription-polymerase chain reaction for determination of caspase 9 and caspase 3 mRNA expression. 3. Cytochrome c release, activation of caspase 9 and caspase 3 and DNA fragmentation were detected 24 h after ischaemia. Dauricine (42 and 84 mg/kg) pretreatment improved histopathological recovery, diminished DNA fragmentation and reduced cytochrome c release and activation of caspase 9 and caspase 3 in the penumbra at 24 h. 4. These findings suggest that dauricine attenuates apoptosis in the penumbra after transient focal cerebral ischaemia. The infarct-reducing effects of dauricine may be due, in part, to the inhibition of apoptotic cell death via a mitochondrial pathway in the penumbra.
Li
Yan-Hong
YH
Department of Clinical Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
Gong
Pei-Li
PL
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*
D000470:Alkaloids; D044182:Benzylisoquinolines; D018696:Neuroprotective Agents; D044005:Tetrahydroisoquinolines; C035934:dauricine; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9