Moyamoya disease (MMD) is characterized by progressive occlusion of the intracranial internal carotid arteries, leading to ischemic and hemorrhagic events. Significant clinical differences exist between ischemic and hemorrhagic MMD. To understand the molecular profiles in the cerebrospinal fluid (CSF) of MMD patients, we investigated 62 secreted factors in both MMD subtypes (ischemic and hemorrhagic) and examined their relationship with preoperative perfusion status, the extent of postoperative angiographic revascularization, and functional outcomes. Intraoperative CSF was collected from 32 control and 71 MMD patients (37 ischemic and 34 hemorrhagic). Multiplex Luminex assay analysis showed that 41 molecules were significantly elevated in both MMD subtypes when compared to controls, including
platelet-derived growth factor-BB (
PDGF-BB),
plasminogen activator inhibitor 1 (PAI-1), and
intercellular adhesion molecule 1 (ICAM1) (p < 0.001). Many of these secreted
proteins have not been previously reported in MMD, including
interleukins (IL-2, IL-4, IL-5, IL-7, IL-8, IL-9, IL-17, IL-18, IL-22, and IL-23) and C-X-C motif
chemokines (CXCL1 and CXCL9). Pathway analysis indicated that both MMD subtypes exhibited similar cellular/molecular functions and pathways, including cellular activation, migration, and inflammatory response. While
neuroinflammation and dendritic cell pathways were activated in MMD patients,
lipid signaling pathways involving
nuclear receptors,
peroxisome proliferator-activated receptor (
PPAR), and
liver X receptors (LXR)/
retinoid X receptors (RXR) signaling were inhibited.
IL-13 and
IL-2 were negatively correlated with preoperative cerebral perfusion status, while 7 factors were positively correlated with the extent of postoperative revascularization. These elevated
cytokines,
chemokines, and
growth factors in CSF may contribute to the pathogenesis of MMD and represent potential future therapeutic targets.