Delayed postconditionig initiates additive mechanism necessary for survival of selectively vulnerable neurons after transient ischemia in rat brain.
1. The aim of this study was to validate the role of postconditioning, used 2 days after lethal ischemia, for protection of selectively vulnerable brain neurons against delayed neuronal death. 2. Eight, 10, or 15 min of transient forebrain ischemia in rat (four-vessel occlusion model) was used as initial lethal ischemia. Fluoro Jade B, the marker of neurodegeneration, and NeuN, a specific neuronal marker were used for visualization of changes 7 or 28 days after ischemia without and with delayed postconditioning. 3. Our results confirm that postconditioning if used at right time and with optimal intensity can prevent process of delayed neuronal death. At least three techniques, known as preconditioners, can be used as postconditioning: short ischemia, 3-nitropropionic acid and norepinephrine. A cardinal role for the prevention of death in selectively vulnerable neurons comprises synthesis of proteins during the first 5 h after postconditioning. Ten minutes of ischemia alone is lethal for 70% of pyramidal CA1 neurons in hippocampus. Injection of inhibitor of protein synthesis (Cycloheximide), if administered simultaneously with postconditioning, suppressed beneficial effect of postconditioning and resulted in 50% of CA1 neurons succumbing to neurodegeneration. Although, when Cycloheximide was injected 5 h after postconditioning, this treatment resulted in survival of 90% of CA1 neurons. 4. Though postconditioning significantly protects hippocampal CA1 neurons up to 10 min of ischemia, its efficacy at 15 min ischemia is exhausted. However, protective impact of postconditioning in less-sensitive neuronal populations (cortex and striatum) is very good after such a damaging insult like 15 min ischemia. This statement also means that up to 15 min of ischemia, postconditioning does not induce cumulation of injuries produced by the first and the second stress.
Burda
Jozef
J
Institute of Neurobiology, Slovak Academy of Sciences, Kosice, Slovakia. burda@saske.sk
Danielisová
Viera
V
Némethová
Miroslava
M
Gottlieb
Miroslav
M
Matiasová
Milina
M
Domoráková
Iveta
I
Mechírová
Eva
E
Feriková
Marianna
M
Salinas
Matilde
M
Burda
Rastislav
R
D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology / Q000628:therapy*; D002470:Cell Survival; D019194:Ischemic Preconditioning / Q000379:methods*; D009474:Neurons / Q000473:pathology*; D014176:Protein Biosynthesis / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors