Effect of cerebral endothelial glycocalyx on capillary stalling and cerebral blood flow

Abstract

To maintain healthy brain, proper regulation and patency of cerebral microcirculation is important. Endothelial glycocalyx is located in luminal side of vessel wall which has been proposed to have several functions such as cell to cell interaction regulation, sheer stress sensing and vessel permeability regulation but its’ function in brain is still elusive. Meanwhile, brief interruption of capillary flow, i.e. capillary stalling, has been observed not only in normal conditions but also in several diseases that is considered to contribute to disease. Capillary stalling has been considered to be occurred by leukocyte plugging but whether cerebral endothelial glycocalyx (cEG) induces capillary stalling is unknown. Utilizing in vivo imaging techniques, I studied cEG and capillary stalling. In addition, capillary stalling and cEG were quantified in subcortical vascular dementia (SVaD) mouse model. I found less extent of cEG were observed in stalled capillary segments of normal mouse. In addition, enzymatic degradation of cEG induced capillary stalling mainly by leukocyte plugging. Longitudinal cerebral microcirculation imaging revealed increased capillary stalling and reduced cEG extent. In addition, SVaD pathological features, such as gliosis and blood brain barrier disruption, were correlated with severity of capillary stalling. Transcriptomic analysis revealed expression of cEG related genes were changed in SVaD model. In summary, I propose the cEG as a novel modulator of cerebral blood flow.