Multiplex Profiling of Secreted Factors in the Cerebrospinal Fluid of Moyamoya Disease Patients

Abstract

Abstract INTRODUCTION Moyamoya disease (MMD) is characterized by progressive occlusion of the internal cerebral arteries. We profiled 62 secreted factors in the cerebrospinal fluid (CSF) of MMD patients, and correlated the levels with the extent of neovascularization and functional outcomes following a revascularization procedure. METHODS CSF from angiographically confirmed MMD was collected. All MMD patients had undergone the revascularization procedure usually in the form of direct superficial temporal artery to middle cerebral artery bypass. Three groups were classified: 32 controls (Chiari or microvascular decompression), 37 patients with MMD (ischemic), and 34 patients with MMD (hemorrhagic). CSF proteins were measured using the multiplex luminex assay. Differential differences were conducted with least mean square (LMS) with CHEX4 as a covariate. All P-values are corrected by the Tukey test. An ELISA was also used to quantitate the level of cellular retinoic acid binding proteins (CRBP1) in CSF samples. Functional outcomes were assessed using the modified Rankin scale score (mRS), and Matsushima criteria was used for grading the neovascularization. RESULTS A total of 40 of 62 secreted factors were significantly elevated in both MMD groups in relation to controls. The most highly secreted CSF proteins include platelet-derived growth factor bb, chemokine ligand 5, and plasminogen activator inhibitor 1 (P < .001). CRBP1 and other growth factors such as brain-derived nerve growth factor, basic fibroblast growth factor, and vascular endothelial growth factor were elevated in both MMD groups (P < .01). These factors are involved in the inflammatory responses, including activation and migration of immune cells and angiogenesis. We also observed several unique genes that differ between the 2 MMD groups (ischemic vs hemorrhagic). CONCLUSION CSF analysis revealed that a number of cytokines, chemokines, and growth factors are elevated in the MMD. Increased CRBP1 in MMD is consistent with the literature and potentially causes an increase of growth factors and cytokines contributing to the pathogenesis.