Abstract
Reopening of the cerebral artery after occlusion often results in “no-reflow” that has been attributed to the death and contraction (rigor mortis) of pericytes. Since this hypothesis still needs to be confirmed, we explored the effects of oxygen glucose deprivation (OGD) on viability and cell death of primary rat pericytes, in the presence or absence of neurovascular unit-derived cytokines. Two morphodynamic parameters, single cell membrane mobility (SCMM) and fractal dimension (Df), were used to analyze the cell contractions and membrane complexity before and after OGD. We found a marginal reduction in cell viability after 2–6 h OGD; 24 h OGD caused a large reduction in viability and a large increase in the number of apoptotic and dead cells. Application of erythropoietin (EPO), or a combination of EPO and endothelial growth factor (VEGFA1−165) during OGD significantly reduced cell viability; application of Angiopoietin 1 (Ang1) during OGD caused a marginal, insignificant increase in cell viability. Simultaneous application of EPO, VEGFA1−165, and Ang1 significantly increased cell viability during 24 h OGD. Twenty minutes and one hour OGD both significantly reduced SCMM compared to pre-OGD values, while no significant difference was seen in SCMM before and after 3 h OGD. There was a significant decrease in membrane complexity (Df) at 20 min during the OGD that disappeared thereafter. In conclusion, OGD transiently affected cell mobility and shape, which was followed by apoptosis in cultured pericytes. Ang1 may have a potentiality for preventing from the OGD-induced apoptosis. Further studies could clarify the relationship between cell contraction and apoptosis during OGD.
Highlights
Pericytes wrap capillaries and express contractile proteins, so they could potentially regulate capillary diameter by constricting or relaxing their processes (Winkler et al, 2017)
The data from this study suggest that pericytes in primary culture represented a heterogenous population of cells; they could survive oxygen glucose deprivation (OGD) for relatively long periods of time, if rrEPO, rrVEGF, and rrAng1 were added in the cell culture medium
The only source of glucose during OGD could be from glycogen
Summary
Pericytes wrap capillaries and express contractile proteins, so they could potentially regulate capillary diameter by constricting or relaxing their processes (Winkler et al, 2017). Whether or not they really control cerebral blood flow (CBF) in vivo is not clear. A study that used loss-of-function pericyte-deficient mice has shown that pericyte degeneration reduces capillary blood flow responses to neuronal activity (Kisler et al, 2017).
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