Perihematomal mitochondrial dysfunction after intracerebral hemorrhage.
OBJECTIVE
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 approximately 40% lower than that of control patients (


METHODS
129+/-39 versus ICH: 76+/-28 nmol O2/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.
Kim-Han
Jeong Sook
JS
Department of Neurology, Washington University, St. Louis, MO, USA.
Kopp
Sarah J
SJ
Dugan
Laura L
LL
Diringer
Michael N
MN
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000328:Adult; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000378:metabolism* / Q000601:surgery; D002560:Cerebrovascular Circulation; D005260:Female; D006406:Hematoma / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D007501:Iron / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption
D000255:Adenosine Triphosphate; D007501:Iron; D010100:Oxygen