Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats.
OBJECTIVE
The mechanisms of brain edema formation following spontaneous intracerebral hemorrhage (ICH) are not well understood. In previous studies, no significant edema formation has been found 24 hours after infusion of packed red blood cells (RBCs) into the brain of a rat or pig; however, there is evidence that hemoglobin can be neurotoxic. In this study, the authors reexamined the role of RBCs and hemoglobin in edema formation after ICH.


METHODS
The experiments involved infusion of whole blood, packed RBCs, lysed RBCs, rat hemoglobin, or thrombin into the right basal ganglia of Sprague-Dawley rats. The animals were killed at different time points and brain water and ion contents were measured. The results showed that lysed autologous erythrocytes, but not packed erythrocytes, produced marked brain edema 24 hours after infusion and that this edema formation could be mimicked by hemoglobin infusion. Although infusion of packed RBCs did not produce dramatic brain edema during the first 2 days, it did induce a marked increase in brain water content 3 days postinfusion. Edema formation following thrombin infusion peaked at 24 to 48 hours. This is earlier than the peak in edema formation that follows ICH, suggesting that there is a delayed, nonthrombin-mediated, edemogenic component of ICH.


CONCLUSIONS
These results demonstrate that RBCs play a potentially important role in delayed edema development after ICH and that RBC lysis and hemoglobin toxicity may be useful targets for therapeutic intervention.
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Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor 48109-0532, USA. guohuaxi@umich.edu
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D000818:Animals; D001929:Brain Edema / Q000097:blood* / Q000209:etiology*; D002543:Cerebral Hemorrhage / Q000097:blood* / Q000150:complications*; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D008297:Male; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D013997:Time Factors; D014867:Water / Q000378:metabolism
D006454:Hemoglobins; D014867:Water; D012964:Sodium; D011188:Potassium