Mitochondrial hyperoxidation signals residual intracellular dysfunction after global ischemia in rat neocortex

M. Rosenthal, Z. C. Feng, C. N. Raffin, M. Harrison, Thomas Sick

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Reperfusion after global ischemia (10-60 min in duration) in rat neocortex most commonly provoked transient hyperoxidation of mitochondrial electron carriers, tissue hyperoxygenation, and CBF hyperemia. These responses were normally accompanied by recovery of K+ homeostasis and EEG spike activity. Goals of this research were to understand putative relationships among these postreperfusion events with special emphasis on determining whether mitochondrial hyperoxidation results from intracellular changes that may modulate residual damage. The amplitude of postischemic mitochondrial hyperoxidation (PIMHo) did not increase when CBF increased above an apparent threshold during reperfusion, and tissue hyperoxygenation was not required for PIMHo to occur or to continue. These findings suggest that PIMHo is not merely a response to increased CBF and tissue hyperoxygenation; rather, PIMHo is modulated, at least in part, by residual intracellular derangements that limit mitochondrial electron transport. This suggestion was supported by observations that NAD became hyperoxidized after reoxygenation in anoxic hippocampal slices. Also, PIMHo occurred and subsequently resolved in many animals, but K+(o) never was cleared fully to baseline and/or EEG spike activity never was evident. One suggestion is that PIMHo signals or initiates residual intracellular derangements that in turn impair electrical and metabolic recovery of cerebral neurons after ischemia; an alternative suggestion is that PIMHo and tissue hyperoxygenation are not the sole factors modulating the immediate restoration of electrical activity after ischemia. Present data also support the following: Decreased oxygen consumption, despite adequate oxygen delivery, likely contributes to tissue hyperoxygenation after ischemia; and mitochondrial hyperoxidation is modulated by a limitation in the supply of electrons to the mitochondrial respiratory chain.

Original languageEnglish
Pages (from-to)655-665
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume15
Issue number4
StatePublished - Jan 1 1995

Fingerprint

Neocortex
Ischemia
Electron Transport
Reperfusion
Electroencephalography
Electrons
Hyperemia
Anniversaries and Special Events
Oxygen Consumption
NAD
Homeostasis
Oxygen
Neurons
Research

Keywords

  • Cerebral cortex
  • Cytochrome a,a
  • Ischemia
  • Oxygen
  • Potassium
  • Reperfusion

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Neuroscience(all)

Cite this

Mitochondrial hyperoxidation signals residual intracellular dysfunction after global ischemia in rat neocortex. / Rosenthal, M.; Feng, Z. C.; Raffin, C. N.; Harrison, M.; Sick, Thomas.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 15, No. 4, 01.01.1995, p. 655-665.

Research output: Contribution to journalArticle

Rosenthal, M. ; Feng, Z. C. ; Raffin, C. N. ; Harrison, M. ; Sick, Thomas. / Mitochondrial hyperoxidation signals residual intracellular dysfunction after global ischemia in rat neocortex. In: Journal of Cerebral Blood Flow and Metabolism. 1995 ; Vol. 15, No. 4. pp. 655-665.
@article{f8c0fe316a14426895d21e608851dec1,
title = "Mitochondrial hyperoxidation signals residual intracellular dysfunction after global ischemia in rat neocortex",
abstract = "Reperfusion after global ischemia (10-60 min in duration) in rat neocortex most commonly provoked transient hyperoxidation of mitochondrial electron carriers, tissue hyperoxygenation, and CBF hyperemia. These responses were normally accompanied by recovery of K+ homeostasis and EEG spike activity. Goals of this research were to understand putative relationships among these postreperfusion events with special emphasis on determining whether mitochondrial hyperoxidation results from intracellular changes that may modulate residual damage. The amplitude of postischemic mitochondrial hyperoxidation (PIMHo) did not increase when CBF increased above an apparent threshold during reperfusion, and tissue hyperoxygenation was not required for PIMHo to occur or to continue. These findings suggest that PIMHo is not merely a response to increased CBF and tissue hyperoxygenation; rather, PIMHo is modulated, at least in part, by residual intracellular derangements that limit mitochondrial electron transport. This suggestion was supported by observations that NAD became hyperoxidized after reoxygenation in anoxic hippocampal slices. Also, PIMHo occurred and subsequently resolved in many animals, but K+(o) never was cleared fully to baseline and/or EEG spike activity never was evident. One suggestion is that PIMHo signals or initiates residual intracellular derangements that in turn impair electrical and metabolic recovery of cerebral neurons after ischemia; an alternative suggestion is that PIMHo and tissue hyperoxygenation are not the sole factors modulating the immediate restoration of electrical activity after ischemia. Present data also support the following: Decreased oxygen consumption, despite adequate oxygen delivery, likely contributes to tissue hyperoxygenation after ischemia; and mitochondrial hyperoxidation is modulated by a limitation in the supply of electrons to the mitochondrial respiratory chain.",
keywords = "Cerebral cortex, Cytochrome a,a, Ischemia, Oxygen, Potassium, Reperfusion",
author = "M. Rosenthal and Feng, {Z. C.} and Raffin, {C. N.} and M. Harrison and Thomas Sick",
year = "1995",
month = "1",
day = "1",
language = "English",
volume = "15",
pages = "655--665",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Mitochondrial hyperoxidation signals residual intracellular dysfunction after global ischemia in rat neocortex

AU - Rosenthal, M.

AU - Feng, Z. C.

AU - Raffin, C. N.

AU - Harrison, M.

AU - Sick, Thomas

PY - 1995/1/1

Y1 - 1995/1/1

N2 - Reperfusion after global ischemia (10-60 min in duration) in rat neocortex most commonly provoked transient hyperoxidation of mitochondrial electron carriers, tissue hyperoxygenation, and CBF hyperemia. These responses were normally accompanied by recovery of K+ homeostasis and EEG spike activity. Goals of this research were to understand putative relationships among these postreperfusion events with special emphasis on determining whether mitochondrial hyperoxidation results from intracellular changes that may modulate residual damage. The amplitude of postischemic mitochondrial hyperoxidation (PIMHo) did not increase when CBF increased above an apparent threshold during reperfusion, and tissue hyperoxygenation was not required for PIMHo to occur or to continue. These findings suggest that PIMHo is not merely a response to increased CBF and tissue hyperoxygenation; rather, PIMHo is modulated, at least in part, by residual intracellular derangements that limit mitochondrial electron transport. This suggestion was supported by observations that NAD became hyperoxidized after reoxygenation in anoxic hippocampal slices. Also, PIMHo occurred and subsequently resolved in many animals, but K+(o) never was cleared fully to baseline and/or EEG spike activity never was evident. One suggestion is that PIMHo signals or initiates residual intracellular derangements that in turn impair electrical and metabolic recovery of cerebral neurons after ischemia; an alternative suggestion is that PIMHo and tissue hyperoxygenation are not the sole factors modulating the immediate restoration of electrical activity after ischemia. Present data also support the following: Decreased oxygen consumption, despite adequate oxygen delivery, likely contributes to tissue hyperoxygenation after ischemia; and mitochondrial hyperoxidation is modulated by a limitation in the supply of electrons to the mitochondrial respiratory chain.

AB - Reperfusion after global ischemia (10-60 min in duration) in rat neocortex most commonly provoked transient hyperoxidation of mitochondrial electron carriers, tissue hyperoxygenation, and CBF hyperemia. These responses were normally accompanied by recovery of K+ homeostasis and EEG spike activity. Goals of this research were to understand putative relationships among these postreperfusion events with special emphasis on determining whether mitochondrial hyperoxidation results from intracellular changes that may modulate residual damage. The amplitude of postischemic mitochondrial hyperoxidation (PIMHo) did not increase when CBF increased above an apparent threshold during reperfusion, and tissue hyperoxygenation was not required for PIMHo to occur or to continue. These findings suggest that PIMHo is not merely a response to increased CBF and tissue hyperoxygenation; rather, PIMHo is modulated, at least in part, by residual intracellular derangements that limit mitochondrial electron transport. This suggestion was supported by observations that NAD became hyperoxidized after reoxygenation in anoxic hippocampal slices. Also, PIMHo occurred and subsequently resolved in many animals, but K+(o) never was cleared fully to baseline and/or EEG spike activity never was evident. One suggestion is that PIMHo signals or initiates residual intracellular derangements that in turn impair electrical and metabolic recovery of cerebral neurons after ischemia; an alternative suggestion is that PIMHo and tissue hyperoxygenation are not the sole factors modulating the immediate restoration of electrical activity after ischemia. Present data also support the following: Decreased oxygen consumption, despite adequate oxygen delivery, likely contributes to tissue hyperoxygenation after ischemia; and mitochondrial hyperoxidation is modulated by a limitation in the supply of electrons to the mitochondrial respiratory chain.

KW - Cerebral cortex

KW - Cytochrome a,a

KW - Ischemia

KW - Oxygen

KW - Potassium

KW - Reperfusion

UR - http://www.scopus.com/inward/record.url?scp=0029073811&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029073811&partnerID=8YFLogxK

M3 - Article

C2 - 7790415

AN - SCOPUS:0029073811

VL - 15

SP - 655

EP - 665

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 4

ER -