Abstract TP454: Immunological Responses in Patients With Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Pilot Study

Abstract

Introduction: Cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) are frequently observed after aneurysmal subarachnoid hemorrhage (aSAH) and contribute to neurocognitive decline and worse outcomes. We hypothesize that aSAH initiates a cascade of neuroinflammatory events which contributes to the development of DCI. Methods: Patients who presented with aSAH requiring external ventricular drainage (EVD) for concomitant hydrocephalus were prospectively enrolled. Cerebrospinal fluid (CSF) samples were collected at different time-points relative to index aSAH injury: acute (days 0-1); pre-vasospasm (days 2-5); vasospasm peak (days 6-9) and post-vasospasm (days 10+). Presence and severity of CVS were assessed using CTA/CTP scans and clinical exam. VEGF and MMP9 (immune affectors) protein levels in the CSF were quantified using ELISA. Mobilization of the immune system was characterized by quantification of innate and adaptive immune cells in the CSF using flow cytometry. Production of inflammatory effector proteins was evaluated using intracellular cytokine staining. Results: Of 13 patients analyzed, 6 (46.2%) experienced CVS. Levels of VEGF and MMP9 were consistently higher in aSAH patients who developed CVS, with the highest difference occurring at the acute phase. Similarly, cellularity analysis revealed elevated counts of monocytes (CD11b + ) in the CSF during the acute phase, with progressive decline at later phases. Microglia (CD45 dim CD11b + ) cells were found to be significantly increased at the post-vasospasm phase. A higher percentage of IFN-γ production cytotoxic T helper cells were found at the acute phase, while the later time points revealed an elevated leveled of CD45RA - CD27 + cytotoxic T cells. Conclusion: Our preliminary data shows an active production of proteins with known immunological functions, mobilization of innate cells, production of inflammatory mediators by adaptive immune cells and altered differentiation status. Our overall goal is to determine if there are potential targets of immunomodulatory therapies which can be used to prevent or treat vasospasms and its related deleterious outcomes.