Postconditioning and anticonditioning: possibilities to interfere to evoked apoptosis.
The aim of this study was to validate the ability of postconditioning, used 2 days after kainate intoxication, to protect selectively vulnerable hippocampal CA1 neurons against delayed neuronal death. Kainic acid (8 mg/kg, i.p.) was used to induce neurodegeneration of pyramidal CA1 neurons in rat hippocampus. Fluoro Jade B, the specific marker of neurodegeneration, and NeuN, a specific neuronal marker were used for visualization of changes 7 days after intoxication without and with delayed postconditioning (norepinephrine, 3.1 mumol/kg i.p., 2 days after kainate administration) and anticonditioning (Extract of Ginkgo biloba, 40 mg/kg p.o used simultaneously with kainate). Morris water maze was used on 6th and 7th day after kainate to test learning and memory capabilities of animals. Our results confirm that postconditioning if used at right time and with optimal intensity is able to prevent delayed neuronal death initiated not only by ischemia but kainate intoxication, too. The protective effect of repeated stress-postconditioning was suppressed if extract of Ginkgo biloba (EGb 761, 40 mg/kg p.o.) has been administered together with kainic acid. It seems that combination of lethal stress and antioxidant treatment blocks the activation of endogenous protecting mechanism known as ischemic tolerance, aggravates neurodegeneration and, after repeated stress is able to cause cumulative damage. This observation could be very valuable in situation when the aim of treatment is elimination of unwanted cell population from the organism.
Burda
Jozef
J
Institute of Neurobiology, Slovak Academy of Sciences, 04001 Kosice, Slovakia. burda@saske.sk
Danielisová
Viera
V
Némethová
Miroslava
M
Gottlieb
Miroslav
M
Kravcuková
Petra
P
Domoráková
Iveta
I
Mechírová
Eva
E
Burda
Rastislav
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects*; D005452:Fluoresceins; D020441:Ginkgo biloba; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000633:toxicity; D018782:Maze Learning; D009410:Nerve Degeneration / Q000139:chemically induced*; D009474:Neurons / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D009930:Organic Chemicals; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D000096983:Ginkgo Extract
D005452:Fluoresceins; D007608:Kainic Acid; D009638:Norepinephrine; D009930:Organic Chemicals; D010936:Plant Extracts; C435731:fluoro jade; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract