Abstract TP487: Comprehensive Profiling of Secreted Factors in the Cerebrospinal Fluid of Moyamoya Disease Patients

Abstract

Background: Moyamoya disease (MMD) is a chronic cerebrovascular disease characterized by progressive occlusion of the internal carotid arteries leading to ischemic and hemorrhagic events. The underlying pathogenesis of MMD remains unclear. In this study we investigated key secreted molecules in the cerebrospinal fluid (CSF) of MMD patients including relation to the extent of neovascularization and eventual functional outcomes. Methods: This study included intraoperative CSF collected from 32 controls (Chiari malformation and cranial nerve hyperactive syndromes) and 73 MMD patients (ischemic: 39; hemorrhagic: 34) that underwent combined direct and indirect superficial temporal artery-middle cerebral artery revascularization procedure. 62 factors were analyzed using multiplex luminex assay, including angiogenic growth factors, cytokines, and chemokines. Cellular retinoic acid binding protein (CRBP1) was also measured using ELISA. Functional outcome was assessed using the modified Rankin scale score (mRS). Matsushima criteria was used for grading the neovascularization. Results: Forty molecules were significantly elevated in both MMD subtypes in comparison with controls. The common top highly secreted CSF proteins included platelet-derived growth factor bb, chemokine ligand 5 and plasminogen activator inhibitor 1 (p<0.001). CRBP1 and other growth factors such as brain-derived nerve growth factor and basic fibroblast growth factor were also elevated in both MMD subtypes (p<0.01). Our results also revealed a number of proteins not previously reported in MMD. Ingenuity pathway analysis indicated that the ischemic and hemorrhagic MMD subtypes exhibited similar cellular/molecular functions and pathways including cellular activation, migration and inflammatory response. Interestingly, while neuro-inflammation and dendritic cell pathways were activated in MMD patients, lipid signaling pathways involving nuclear receptors PPAR and LXR/RXR signaling were inhibited. Conclusions: CSF analysis revealed that a number of cytokines, chemokines and growth factors are elevated in both MMD subtypes. These molecules potentially contribute to the pathogenesis of MMD and could be potential future therapeutic targets.