Bradykinin postconditioning protects pyramidal CA1 neurons against delayed neuronal death in rat hippocampus.
OBJECTIVE
The present study was undertaken to evaluate possible neuroprotective effect of bradykinin against delayed neuronal death in hippocampal CA1 neurons if applied two days after transient forebrain ischemia in the rat.


METHODS
Transient forebrain ischemia was induced in male Wistar rats by four-vessel occlusion for 8 min. To assess efficacy of bradykinin as a new stressor for delayed postconditioning we used two experimental groups of animals: ischemia 8 min and 3 days of survival, and ischemia 8 min and 3 days of survival with i.p. injection of bradykinin (150 microg/kg) applied 48 h after ischemia.


RESULTS
We found extensive neuronal degeneration in the CA1 region at day 3 after ischemia/reperfusion. The postischemic neurodegeneration was preceded by increased activity of mitochondrial enzyme MnSOD in cytoplasm, indicating release of MnSOD from mitochondria in the process of delayed neuronal death. Increased cytosolic cytochrome c and subsequently caspase-3 activation are additional signs of neuronal death via the mitochondrial pathway. Bradykinin administration significantly attenuated ischemia-induced neuronal death, and also suppressed the release of MnSOD, and cytochrome c, and prevented caspase-3 activation.


CONCLUSIONS
Bradykinin can be used as an effective stressor able to prevent mitochondrial failure leading to apoptosis-like delayed neuronal death in postischemic rat hippocampus.
Danielisová
Viera
V
Institute of Neurobiology, Slovak Academy of Sciences, Kosice, Slovak Republic. danielis@saske.sk
Gottlieb
Miroslav
M
Némethová
Miroslava
M
Kravcuková
Petra
P
Domoráková
Iveta
I
Mechírová
Eva
E
Burda
Jozef
J
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001920:Bradykinin / Q000627:therapeutic use*; D001921:Brain / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology*; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000150:complications / Q000473:pathology*; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology*; D009474:Neurons / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D045304:Cytochromes c; D013482:Superoxide Dismutase; D053148:Caspase 3; D001920:Bradykinin