title: Effect of Bradykinin Postconditioning on Ischemic and Toxic Brain Damage.
abstract: Brain damage caused by ischemia or toxic agents leads in selectively vulnerable regions to apoptosis-like delayed neuronal death and can result in irreversible damage. Selectively vulnerable neurons of the CA1 area of hippocampus are particularly sensitive to ischemic damage. We investigated the effects of bradykinin (BR) postconditioning on cerebral ischemic and toxic injury. Transient forebrain ischemia was induced by four-vessel occlusion for 10 min and toxic injury was induced by trimethyltin (TMT, 8 µg/kg i.p.). BR as a postconditioner at a dose of 150 µg/kg was applied intraperitoneally 48 h after ischemia or TMT intoxication. Experimental animals were divided into groups according to the length of survival (short-3 and 7 days, and long-28 days survival) and according to the applied ischemic or toxic injury. Glutamate concentration was lowered in both CA1 and dentate gyrus areas of hippocampus after the application of BR postconditioning in both ischemic and toxic brain damage. The number of degenerated neurons in the hippocampal CA1 region was significantly lower in BR-treated ischemic and toxic groups compared to vehicle group. The behavioral test used in our experiments confirms also the memory improvement in conditioned animals. The rats' ability to form spatial maps and learn was preserved, which is visible from our Barnes maze results. By using the methods of delayed postconditioning is possible to stimulate the endogenous protective mechanisms of the organism and induce the neuroprotective effect. In this study we demonstrated that BR postconditioning, if applied before the onset of irreversible neurodegenerative changes, induced neuroprotection against ischemic or toxic injury.
authors.affiliation: Department of Neurochemistry, Institute of Neurobiology, Slovak Academy of Sciences, Šoltésovej 4-6, 04001, Kosice, Slovak Republic, lalkovicova@saske.sk.
authors.forename: Mária
authors.initials: M
authors.lastname: Lalkovičová
authors.forename: Petra
authors.initials: P
authors.lastname: Bonová
authors.forename: Jozef
authors.initials: J
authors.lastname: Burda
authors.forename: Viera
authors.initials: V
authors.lastname: Danielisová
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000378:metabolism; D057775:Ischemic Postconditioning / Q000379:methods*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018696:Neuroprotective Agents; D001920:Bradykinin