Abstract TMP23: Inflammasome-derived Caspase-1 is Elevated in the Cerebrospinal Fluid of Subarachnoid Hemorrhage Patients and Correlated to Outcome

Abstract

Introduction: The role of neuroinflammation following aneurysmal subarachnoid hemorrhage (SAH) and its relationship to outcome is the subject of many ongoing studies. The proteolytic enzyme, caspase-1, activated by the inflammasome complex, is known to contribute to numerous downstream pro-inflammatory effects. In this study, we investigated caspase-1 activity in the cerebrospinal fluid (CSF) of SAH patients and its association to outcome. Methods: SAH patients were recruited from a regional stroke referral center. CSF samples from 18 SAH subjects were collected via an external ventricular drain and obtained within 72 hours of the onset of symptoms. For control subjects, we collected the CSF from 9 patients undergoing lumbar puncture with normal CSF and normal brain MRI. Caspase-1 activity was measured using commercially available luminescence assays. SAH subjects were categorized at hospital discharge into those with good outcomes (Glasgow Outcome Scale, GOS, of 4-5) and poor outcomes (GOS of 1-3). The levels of caspase-1 activity in various groups were analyzed using Mann-Whitney and Pearson correlation tests. Caspase-1 activity was also adjusted by initial severity of bleed using analysis of covariance (ANCOVA). Results: Caspase-1 levels from SAH patients were significantly higher than that measured from the control group (mean 1.06x10-2 vs 1.90x10-3 counts per second (CPS)/μl*min), p = 0.0002). Within the SAH group, 10 patients (55.6%) had good outcomes and 8 patients (44.4%) had poor outcomes. Caspase-1 activity was significantly higher in the poor outcome group (mean 1.54x10-2 vs 1.60x10-3 CPS/μl*min), p = 0.0012). Additionally, caspase-1 activity had a statistically significant correlation with GOS score (r = -0.60; p = 0.0100). When adjusted for initial severity of bleed, the difference in caspase-1 activity in good vs. poor outcome remained significant (adjusted mean 7.10x10-3 vs. 2.54x10-2 CPS/μl*min, p=0.004). Conclusions: The inflammasome-dependent protein caspase-1 is elevated in CSF early after SAH and higher in those with poor functional outcome. Inflammasome activity therefore may serve as a novel biomarker to predict outcome shortly after aneurysm rupture.