Published Online
on June 2, 2005

A more recent version of this article appeared on July 1, 2005

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Submitted on January 17, 2005
Revised on April 15, 2005
Accepted on May 2, 2005

The Deleterious or Beneficial Effects of Different Agents in Intracerebral Hemorrhage. Think Big, Think Small, or Is Hematoma Size Important?

Richard F. Keep PhD^*; Guohua Xi MD; Ya Hua MD; and Julian T. Hoff MD

From the Departments of Neurosurgery (R.F.K., G.X. Y.H., J.T.H.) and Physiology (R.F.K.), University of Michigan, Ann Arbor, Mich.

^* To whom correspondence should be addressed. E-mail: rkeep{at}umich.edu.

Background and Purpose--Thrombin, heme oxygenase, complement, microglia activation, and leukocyte infiltration are all actively upregulated in intracerebral hemorrhage (ICH). Experimental evidence suggests that all these factors are involved in ICH-induced brain injury. This suggests a scenario whereby ICH actively (through gene and protein upregulation) induces pathways that result in brain injury.

Summary of Review--In this comment, we suggest a potential answer to this conundrum. The upregulation of these factors may have been an evolutionary adaptation to limit brain injury during small hematomas (microbleeds). There is evidence that low levels of thrombin and heme oxygenase limit brain injury. In contrast, the excessive upregulation of these same factors may have a harmful effect after a large hematoma.

Conclusion--The mechanisms upregulated to limit brain injury after microbleeds may also induce injury after large hematomas. The effect of hematoma size on the mechanisms involved in ICH-induced brain injury and the implications of any such effect on clinical therapies merit further investigation.

Key words: inflammation • iron • thrombin

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