Abstract TP426: Candidate CSF Cytokine and Chemokine Biomarkers for Vasospasm and Poor Outcome in Human Subarachnoid Hemorrhage
Introduction: Growing evidence suggest inflammation plays a key role in the pathogenesis of vasospasm (VSP) and secondary ischemic injury following subarachnoid hemorrhage (SAH). While elevations of select pro-inflammatory cytokines such interleukin (IL) 6 in cerebrospinal fluid (CSF) are linked to VSP in SAH, it is unclear which cytokines are measurable in SAH CSF. We explore a panel of cytokines and chemokines during peak VSP time window in human SAH in search for novel CSF biomarkers.
Methods: CSF samples were collected through external ventricular drain from a prospective SAH cohort. Clinical outcome was evaluated at 3- and 6-months using modified Rankin scores (mRS). Poor outcome was defined as mRS>2. Angiographic VSP was defined as >50% reduction in caliber of any vessel on post-SAH day 7 cerebral angiogram. In 29 SAH subjects, we compared post-SAH day 5 CSF biomarker profile with respect to outcome and VSP using Milliplex panel (EMD Millipore) with 42 biomarkers. Continuous variables were compared using Wilcoxon rank sum test. Benjamin-Hochberg correction was used for multiple comparisons.
Results: VSP occurred in 45% of the SAH cohort, and 52% of this cohort had good outcome at 3 month. Of the 42 biomarkers, 39 were measurable in SAH CSF. Elevated CSF IL-4 showed strongest trend towards association with good outcome at 3-month (p=0.0049) and at 6-months (p=0.02). Other CSF biomarkers showing trend toward association with outcome include epidermal growth factor (p=0.035), fractalkine (p=0.045), and platelet-derived growth factor AA (p=0.024). Elevation of a different cluster of biomarkers showed trend towards association with VSP: IL-5 (p=0.041), IL-17A (p=0.049), and IL-2 (p=0.047). No single marker reached significance at p<0.05 level after adjustment for multiple comparisons.
Conclusions: Differential expression of cytokine and chemokines are present in CSF post SAH. Results from this small pilot study suggest a possible association between elevation of CSF anti-inflammatory cytokine IL-4 and good SAH outcome. This is consistent with animal studies showing IL-4 attenuates ischemic injury and promotes neuroprotection. Larger targeted studies are necessary to investigate the role of cytokines and specifically CSF IL-4 in SAH outcome.
- © 2012 by American Heart Association, Inc.