Postconditioning and Anticonditioning: Possibilities to Interfere to Evoked Apoptosis
- 138 Downloads
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 μmol/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.
KeywordsHippocampus CA1 Kainic acid Ischemia Neurodegeneration Postconditioning Anticonditioning Delayed neuronal death
This work was sponsored by grants APVV LPP-0235-06, VEGA 2/0141/09 and 1/4237/07. We gratefully acknowledge the expert technical assistance of Viera Ujháziová, and Dana Jurušová.
- Burda J, Matiasova M, Gottlieb M, Danielisova V, Nemethova M, Garcia L, Salinas M, Burda R (2005) Evidence for a role of second pathophysiological stress in prevention of delayed neuronal death in the hippocampal CA1 region. Neurochem Res 30:1397–1405. doi: 10.1007/s11064-005-8510-z PubMedCrossRefGoogle Scholar
- Burda J, Danielisova V, Nemethova M, Gottlieb M, Matiasova M, Domorakova I, Mechirova E, Ferikova M, Salinas M, Burda R (2006) Delayed postconditionig initiates additive mechanism necessary for survival of selectively vulnerable neurons after transient ischemia in rat brain. Cell Mol Neurobiol 26:1139–1149. doi: 10.1007/s10571-006-9036-x CrossRefGoogle Scholar
- Meng X, Cleveland JC Jr, Rowland RT, Mitchell MB, Brown JM, Banerjee A, Harken AH (1996) Norepinephrine-induced sustained myocardial adaptation to ischemia is dependent on alpha 1-adrenoceptors and protein synthesis. J Mol Cell Cardiol 28:2017–2025. doi: 10.1006/jmcc.1996.0194 PubMedCrossRefGoogle Scholar
- Puisieux F, Deplanque D, Bulckaen H, Maboudou P, Gele P, Lhermitte M, Lebuffe G, Bordet R (2004) Brain ischemic preconditioning is abolished by antioxidant drugs but does not up-regulate superoxide dismutase and glutathion peroxidase. Brain Res 1027:30–37. doi: 10.1016/j.brainres.2004.08.067 PubMedCrossRefGoogle Scholar