Functional analysis of Pro-inflammatory properties within the cerebrospinal fluid after subarachnoid hemorrhage in vivo and in vitro.
BACKGROUND
To functionally characterize pro-inflammatory and vasoconstrictive properties of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage (SAH) in vivo and in vitro.


METHODS
The cerebrospinal fluid (CSF) of 10 patients suffering from SAH was applied to the transparent skinfold chamber model in male NMRI mice which allows for in vivo analysis of the microcirculatory response to a superfusat. Microvascular diameter changes were quantified and the numbers of rolling and sticking leukocytes were documented using intravital multifluorescence imaging techniques. Furthermore, the pro-inflammatory properties of CSF were assessed in vitro using a monocyte transendothelial migration assay.


RESULTS
CSF superfusion started to induce significant vasoconstriction on days 4 and 6 after SAH. In parallel, CSF superfusion induced a microvascular leukocyte recruitment, with a significant number of leukocytes rolling (day 6) and sticking (days 2-4) to the endothelium. CSF of patients presenting with cerebral edema induced breakdown of blood vessel integrity in our assay as evidenced by fluorescent marker extravasation. In accordance with leukocyte activation in vivo, significantly higher in vitro monocyte migration rates were found after SAH.


CONCLUSIONS
We functionally characterized inflammatory and vasoactive properties of patients' CSF after SAH in vivo and in vitro. This pro-inflammatory milieu in the subarachnoid space might play a pivotal role in the pathophysiology of early and delayed brain injury as well as vasospasm development following SAH.
Department of Neurosurgery, Charité Universitaetsmedizin, Augustenburger Platz 1, 13353 Berlin, Germany.
Ulf C
UC
Schneider
Jennifer
J
Schiffler
Nahid
N
Hakiy
Peter
P
Horn
Peter
P
Vajkoczy
D000328:Adult; D000368:Aged; D015901:Angiography, Digital Subtraction / Q000379:methods; D000818:Animals; D001929:Brain Edema / Q000209:etiology; D002465:Cell Movement / Q000502:physiology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000209:etiology*; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging; D009000:Monocytes / Q000502:physiology; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid / Q000150:complications*; D013997:Time Factors; D017585:Ultrasonography, Doppler, Transcranial; D020301:Vasospasm, Intracranial / Q000134:cerebrospinal fluid* / Q000209:etiology* / Q000473:pathology