Hemoglobin crystals: a pro-inflammatory potential confounder of rat experimental intracerebral hemorrhage.
In vivo rat hemoglobin crystallization has been reported in lung, liver and kidney, but never following central nervous system injury. In the present study, we examined hemoglobin crystallization following experimental intracerebral hemorrhage (ICH) and its effects on inflammation. Ninety-one rat brains, subjected to either autologous or collagenase ICH, and vehicle controls, were retrospectively examined. In both models, hemoglobin crystals were present in most brains at 24 and 48 h. They were especially prominent at 24 h in autologous ICH brains (2.5% of the hematoma vs 0.6% in collagenase animals; p=0.0001) and, at 5 h, were only present in autologous ICH brains. Crystals were diminishing at 48 h and were absent at 7 days. Crystals appeared in clusters around blood vessels. In both models, at 24 h, crystals appeared strongly chemotactic for neutrophils. This effect was most pronounced in autologous ICH brains (2628+/-182 neutrophils/mm(2) hematoma crystals vs 327+/-54 neutrophils/mm(2) hematoma; p<0.0001). In these animals up to 30% of the total neutrophilic infiltrate was located around crystals. A greater overall neutrophilic infiltrate was seen in autologous ICHs with higher percentages of crystalline hemoglobin (p=0.04 for trend). Although hemoglobin crystallization occurs in both models of ICH, it is particularly prominent following autologous ICH. Accordingly, hemoglobin crystallization may exaggerate the importance of inflammation in this model.
Kleinig
Timothy J
TJ
Discipline of Pathology, University of Adelaide, Adelaide, SA, Australia. timothy.kleinig@adelaide.edu.au
Helps
Stephen C
SC
Ghabriel
Mounir N
MN
Manavis
Jim
J
Leigh
Christopher
C
Blumbergs
Peter C
PC
Vink
Robert
R
D000818:Animals; D002543:Cerebral Hemorrhage / Q000097:blood* / Q000473:pathology*; D003460:Crystallization; D004195:Disease Models, Animal; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism*; D007249:Inflammation / Q000097:blood / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012189:Retrospective Studies; D013997:Time Factors
D006454:Hemoglobins