Evidence for a role of second pathophysiological stress in prevention of delayed neuronal death in the hippocampal CA1 region.
In ischemic tolerance experiment, when we applied 5-min ischemia 2 days before 30-min ischemia, we achieved a remarkable (95.8%) survival of CA1 neurons. However, when we applied 5-min ischemia itself, without following lethal ischemia, we found out 45.8% degeneration of neurons in the CA1. This means that salvage of 40% CA1 neurons from postischemic degeneration was initiated by the second pathophysiological stress. These findings encouraged us to hypothesize that the second pathophysiological stress used 48 h after lethal ischemia can be efficient in prevention of delayed neuronal death. Our results demonstrate that whereas 8 min of lethal ischemia destroys 49.9% of CAI neurons, 10 min of ischemia destroys 71.6% of CA1 neurons, three different techniques of the second pathophysiological stress are able to protect against both: CA1 damage as well as spatial learning/memory dysfunction. Bolus of norepinephrine (3.1 micromol/kg i.p.) used two days after 8 min ischemia saved 94.2%, 6 min ischemia applied 2 days after 10 min ischemia rescued 89.9%, and an injection of 3-nitropropionic acid (20 mg/kg i.p.) applied two days after 10 min ischemia protected 77.5% of CA1 neurons. Thus, the second pathophysiological stress, if applied at a suitable time after lethal ischemia, represents a significant therapeutic window to opportunity for salvaging neurons in the hippocampal CA1 region against delayed neuronal death.
Burda
Jozef
J
Institute of Neurobiology, Slovak Academy of Sciences, Soltésovej 4, Kosice, 040 01, Slovakia. burda@saske.sk
Matiasová
Milina
M
Gottlieb
Miroslav
M
Danielisová
Viera
V
Némethová
Miroslava
M
Garcia
Lidia
L
Salinas
Matilde
M
Burda
Rastislav
R
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival; D006624:Hippocampus / Q000166:cytology / Q000473:pathology; D006801:Humans; D018782:Maze Learning; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar