An effective combination of two different methods of postconditioning.
Ischemic tolerance based on the synthesis of protective proteins acquires its full strength by repeated exposure to stress, and "the end effector of tolerance" may paradoxically be activated by the second or lethal stress, particularly in the case of preconditioning. That happens when an additional nonspecific stressor is applied either before (preconditioning) or after (postconditioning) the period of lethal ischemia. A combination of antioxidants with pre or postconditioning prevents the acquisition of tolerance, and in the case of more severe attacks repeated stress can lead to accumulation of damage. Our attempt to weaken ischemic injury to hippocampal CA1 with antioxidants applied after lethal stress, i.e. before delayed postconditioning, was ineffective. We then tried using rapid postconditioning consisting of 30-s reperfusion alternating with 15-s ischemia repeated three times and applied immediately at the end of lethal ischemia as a tool decreasing post-ischemic production of reactive oxygen species, and combining that with delayed postconditioning consisting of an i.p. injection of Bradykinin 2 days after lethal ischemia. This approach once more confirmed the efficacy of both rapid as well as delayed postconditioning but, more importantly, it demonstrated the possibility of effectively combining these two procedures. Our findings further confirm that in cases of delayed neuronal death, which is practically pathologically-induced apoptosis, there exists a 2-day-wide therapeutic window that can be effectively exploited.
Institute of Neurobiology, Slovak Academy of Sciences, Soltesovej 4, 040 01 Kosice, Slovakia. danielis@saske.sk
Viera
V
Danielisova
Jozef
J
Burda
Miroslava
M
Nemethova
Miroslav
M
Gottlieb
Rastislav
R
Burda
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001920:Bradykinin / Q000008:administration & dosage; D002545:Brain Ischemia / Q000473:pathology / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion
D000975:Antioxidants; D001920:Bradykinin