gms | German Medical Science

Objective: Inflammatory mechanisms have become an interesting target for early and delayed brain injury after acute subarachnoid hemorrhage (SAH). To functionally characterize pro-inflammatory and vasoconstrictive properties of cerebrospinal fluid after SAH in vivo and in vitro.

Methods: 1. The cerebrospinal fluid (CSF) of 10 patients suffering from SAH was applied to the transparent skinfold chamber model in male C57BL/6 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. A correlation to the appearance (clinical, angiography, dopplersonography, Xenon-CT) of cerebral vasospasm was performed 2. The pro-inflammatory properties of CSF were assessed in vitro using a transendothelial monocyte migration assay.

Results: In the skinfold chamber CSF superfusion started to induce significant vasoconstriction on days 2 and 4 after SAH, i.e. days before the clinical diagnosis of cerebral vasospasm. In parallel, CSF superfusion induced a massive microvascular leukocyte recruitment, with high numbers of leukocytes rolling and sticking to the endothelium. CSF of patients presenting with SAH-associated 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: This study reveals a variety of vasoactive properties of patients' CSF after SAH that reach peak activities days before the clinical manifestation of cerebral vasospasm. The pro-inflammatory milieu in the subarachnoid space might play a pivotal role in the pathophysiology of SAH, the induction of cerebral vasospasm and the mechanisms of secondary brain injury.