Abstract
Background: Systemic inflammation with elevated oxidative stress causing neuroinflammation is considered a major factor in the pathogenesis of Parkinson’s disease (PD).The interface between systemic circulation and the brain parenchyma is the blood - brain barrier (BBB), which also plays a role in maintaining neurovascular homeostasis. Relatedly, intermediate vascular inflammation causing BBB dysfunction is a key component of PD pathogenesis. Vascular cell adhesion molecule-1 (VCAM-1) and microRNAs (miRNAs) regulate brain endothelial function, neoangiogenesis, and, in turn, neuronal homeostasis regulation, such that their dysregulation can result in neurodegeneration, such as gray matter atrophy, in PD. In this study, our aim was to evaluate the associations among specific levels of gray matter atrophy, peripheral vascular adhesion molecules, miRNAs, and clinical disease severity in order to achieve a clearer understanding of PD pathogenesis.Methods: Blood samples were collected from 33 patients with PD and 27 healthy volunteers, and the levels of VCAM-1 and several miRNAs in those samples were measured. Voxel-based morphometry (VBM) analysis was performed using 3T magnetic resonance imaging (MRI) and SPM (Statistical Parametric Mapping software program). The associations among the vascular parameter, miRNAs, gray matter volume and clinical disease severity measurements were evaluated by partial correlation analysis.Results: The levels of VCAM-1, miRNA-22 and miRNA-29a expression were significantly elevated in the PD patients. The gray matter volume atrophy in the left parahippocampus, bilateral posterior cingulate gyrus, fusiform gyrus, left temporal gyrus, and cerebellum was significantly correlated with increased clinical disease severity, the upregulation of miRNA levels, and increased vascular inflammation.Conclusions: Patients with PD seem to have abnormal levels of vascular inflammatory markers and miRNAs in the peripheral circulation, and these levels are correlated with specific brain volume changes. This study reinforces the associations among peripheral inflammation, the BBB interface, and gray matter atrophy in PD, and further demonstrates that BBB dysfunction with neurovascular impairment may play an important role in PD progression.
Lipopolysaccharide animal models of Parkinson’s disease: Recent progress and relevance to clinical disease
