Perihematomal mitochondrial dysfunction after intracerebral hemorrhage

Jeong Sook Kim-Han, Sarah A. Kopp, Laura L. Dugan, Michael N. Diringer

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

BACKGROUND AND PURPOSE - Recent measurements in intracerebral hemorrhage (ICH) patients suggest a primary reduction in brain metabolism is responsible for reduced cerebral blood flow and low oxygen extraction surrounding the hematoma. We sought to determine whether reduced mitochondrial respiratory function could account for reduced metabolic demand in ICH patients. METHODS - Brain-tissue samples from 6 patients with acute spontaneous ICH and 6 control patients undergoing brain resection for management of seizure were evaluated. Only tissue removed from the brain adjacent to the hematoma was studied. Specimens were collected in the operating room; mitochondrial studies were begun within 1-hour. Mitochondrial oxygen consumption was measured after the addition of pyruvate, malate, and ADP, followed by oligomycin and carbonylcyanide. RESULTS - The ICH patients ranged in age from 40 to 54 years; 2 were female and half black. Hemorrhages were located in the temporal lobe (3), cerebellum (2) and parietal lobe (1). The average State 3 (active) O2 consumption for mitochondria from ICH patients was ≈40% lower than that of control patients (Controls: 129±39 versus ICH: 76±28 nmol O 2/min per mg protein). With increasing time from hemorrhage to testing there was a progressive decline in State 3 respiration. Reduced State 3 respiration was evident even at 6 hours, whereas at 72 hours, there was essentially no O2 consumption. CONCLUSIONS - These data support the hypothesis that mitochondrial dysfunction and not ischemia is responsible for reduced oxygen metabolism in ICH. They point to a new direction for investigation and development of therapeutic interventions for ICH patients.

Original languageEnglish
Pages (from-to)2457-2462
Number of pages6
JournalStroke
Volume37
Issue number10
DOIs
StatePublished - Oct 2006

Keywords

  • Intracerebral hemorrhage
  • Mitochondria
  • Secondary injury

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