Mitochondrial dysfunction in aging rat brain following transient global ischemia

Kui Xu, Michelle Puchowicz, Xiaoyan Sun, Joseph C. Lamanna

Research output: Chapter in Book/Report/Conference proceedingConference contribution

15 Citations (Scopus)

Abstract

Aged rat brain is more sensitive to reperfusion injury induced by cardiac arrest and resuscitation. The mitochondrial respiratory chain, the major source of free radicals during reperfusion, is likely to be the target of lipid peroxidation. Previous work has shown a higher mortality and lower hippocampal neuronal survival in older rats. 4-hydroxy-2-nonenal (HNE), a major product of lipid peroxidation, was found to be elevated in cortex and brainstem after resuscitation. In this study we investigated the acute changes of mitochondrial function in aging rat brain following cardiac arrest and resuscitation; the effect of an antioxidant, alpha-phenyl-tert-butyl-nitrone (PBN) was also tested. Fischer 344 rats, 6 and 24-month old, were subjected to cardiac arrest (7-10 minutes) and allowed to recover 1 hour after resuscitation. Mitochondria of cortex and brainstem were isolated and assayed for respiratory function. Compared to their respective non-arrested control group, 1h untreated groups (both 6 month and 24 month) had similar state 3 (ADP-stimulated) but higher state 4 (resting state) respiratory rates. The respiratory control ratio (state 3/state 4) of cortex in the 1h untreated group was 26% lower than the non-arrested control group; similar results were found in brainstem. The decreased mitochondrial respiratory function was improved by PBN treatment. HNE-modified mitochondrial proteins were elevated 1h after resuscitation, with an evident change in the aged. Treatment with PBN reduced the elevated HNE production in mitochondria of cortex. The data suggest (i) there is increased sensitivity to lipid peroxidation with aging, (ii) mitochondrial respiratory function related to coupled oxidation decreases following cardiac arrest and resuscitation, and (iii) treatment with antioxidant, such as PBN, reduces the oxidative damage following cardiac arrest and resuscitation.

Original languageEnglish (US)
Title of host publicationOxygen Transport to Tissue XXIX
PublisherSpringer New York
Pages379-386
Number of pages8
ISBN (Print)9780387749105
DOIs
StatePublished - Jan 1 2008

Publication series

NameAdvances in Experimental Medicine and Biology
Volume614
ISSN (Print)0065-2598

Fingerprint

Resuscitation
Rats
Brain
Ischemia
Aging of materials
Heart Arrest
Lipid Peroxidation
Brain Stem
Mitochondria
Lipids
Antioxidants
Induced Heart Arrest
Control Groups
Mitochondrial Proteins
Inbred F344 Rats
Respiratory Rate
Electron Transport
Reperfusion Injury
Adenosine Diphosphate
Reperfusion

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Xu, K., Puchowicz, M., Sun, X., & Lamanna, J. C. (2008). Mitochondrial dysfunction in aging rat brain following transient global ischemia. In Oxygen Transport to Tissue XXIX (pp. 379-386). (Advances in Experimental Medicine and Biology; Vol. 614). Springer New York. https://doi.org/10.1007/978-0-387-74911-2_42

Mitochondrial dysfunction in aging rat brain following transient global ischemia. / Xu, Kui; Puchowicz, Michelle; Sun, Xiaoyan; Lamanna, Joseph C.

Oxygen Transport to Tissue XXIX. Springer New York, 2008. p. 379-386 (Advances in Experimental Medicine and Biology; Vol. 614).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Xu, K, Puchowicz, M, Sun, X & Lamanna, JC 2008, Mitochondrial dysfunction in aging rat brain following transient global ischemia. in Oxygen Transport to Tissue XXIX. Advances in Experimental Medicine and Biology, vol. 614, Springer New York, pp. 379-386. https://doi.org/10.1007/978-0-387-74911-2_42
Xu K, Puchowicz M, Sun X, Lamanna JC. Mitochondrial dysfunction in aging rat brain following transient global ischemia. In Oxygen Transport to Tissue XXIX. Springer New York. 2008. p. 379-386. (Advances in Experimental Medicine and Biology). https://doi.org/10.1007/978-0-387-74911-2_42
Xu, Kui ; Puchowicz, Michelle ; Sun, Xiaoyan ; Lamanna, Joseph C. / Mitochondrial dysfunction in aging rat brain following transient global ischemia. Oxygen Transport to Tissue XXIX. Springer New York, 2008. pp. 379-386 (Advances in Experimental Medicine and Biology).
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