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Delayed Postconditionig Initiates Additive Mechanism Necessary for Survival of Selectively Vulnerable Neurons After Transient Ischemia in Rat Brain

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Abstract

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.

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ACKNOWLEDGMENTS

This work was supported by grants SK-VEGA 2/3219/23 and APVT 51-0219-04. We gratefully acknowledge the expert technical assistance of Viera Ujháziová, Dana Jurušová, and Zuzana Burdová.

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Authors and Affiliations

  1. Institute of Neurobiology, Slovak Academy of Sciences, Košice, Slovakia

    Jozef Burda, Viera Danielisová, Miroslava Némethová, Miroslav Gottlieb & Milina Matiašová

  2. Department of Histology and Embryology, Faculty of Medicine, University of P. J. Šafárik, Košice, Slovakia

    Iveta Domoráková, Eva Mechírová & Marianna Feriková

  3. Department of Biochemistry, Hospital Ramon y Cajal, Madrid, Spain

    Matilde Salinas

  4. Faculty Hospital of L. Pasteur, Košice, Slovakia

    Rastislav Burda

  5. Institute of Neurobiology, Slovak Academy of Sciences, Šoltésovej 4, 040 01, Košice, Slovakia

    Jozef Burda

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  1. Jozef Burda
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Burda, J., Danielisová, V., Némethová, M. et al. Delayed Postconditionig Initiates Additive Mechanism Necessary for Survival of Selectively Vulnerable Neurons After Transient Ischemia in Rat Brain. Cell Mol Neurobiol 26, 1139–1149 (2006). https://doi.org/10.1007/s10571-006-9036-x

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