Published online before print September 7, 2006, doi: 10.1161/01.STR.0000244060.83388.76
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2006;37:2445.)
© 2006 American Heart Association, Inc.
Editorials |
Intracerebral Hematoma
Beyond the Mass Lesion
From the Department of Neurology, University of California, San Francisco, and Veterans Affairs Medical Center, San Francisco, Calif.
Correspondence to Raymond A. Swanson, Department of Neurology, Veterans Affairs Medical Center, 4150 Clement St, San Francisco, CA 94121. E-mail raymond.swanson@va.gov
Key Words: intracranial hemorrhage • mitochondria
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
See related article, pages 2457–2462.
The signs and symptoms of acute intracranial hemorrhage are those of a rapidly developing mass lesion, compounded over time by surrounding edema, and sometimes by brain herniation. These are dramatic, debilitating, and often fatal events, but does the pathophysiology of intracranial hemorrhage extend beyond that of mass effect? Blood contains several factors that are potentially, and in some cases definitively, neurotoxic. Chief among these are hemoglobin and its breakdown products, heme and iron, which exhibit neurotoxicity at low micromolar concentrations through mechanisms involving iron-catalyzed production of reactive oxygen species.1,2 Brain has a variety of defense mechanisms to prevent the formation of reactive iron from blood hemoglobin, including inducible and constitutive heme oxygenases and iron-binding proteins,3 but these are easily overwhelmed by frank hemorrhage.4 Indirect evidence for hematoma toxicity on surrounding brain has come from studies showing reduced extraction of blood oxygen by perihematoma brain tissue.5 Given that heme and iron are potent mitochondrial toxins, one explanation for reduced oxygen extraction in the vicinity of a brain hematoma is a reduced capacity for oxygen use by mitochondria in this region.
The study by Kim-Han et al6 provides additional support for this idea. This study measured rates of oxygen use by mitochondria isolated from the margins of intracerebral hematomas in 6 human subjects. These measurements revealed a roughly 40% reduction in state 3 respiration and 3-fold increase in state 4 respiration in perihematoma samples, relative to putatively normal mitochondria taken from epilepsy surgery sites. State 3
Related Article:
Stroke 2006 37: 2457-2462.