The deleterious or beneficial effects of different agents in intracerebral hemorrhage: think big, think small, or is hematoma size important?
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Keep
Richard F
RF
Department of Neurosurgery, University of Michigan, 5550 Kresge I, Ann Arbor, MI 48109-0532, USA. rkeep@umich.edu
Xi
Guohua
G
Hua
Ya
Y
Hoff
Julian T
JT
D000818:Animals; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000175:diagnosis* / Q000188:drug therapy*; D019143:Evolution, Molecular; D006406:Hematoma / Q000175:diagnosis* / Q000473:pathology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007501:Iron / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology; D017628:Microglia / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D015854:Up-Regulation
D007501:Iron; D006419:Heme Oxygenase (Decyclizing); D013917:Thrombin