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Updated: Aug 1, 2025
Isolation of Primary Murine Brain Microvascular Endothelial Cells
Published on: November 14, 2014
Microvascular Environment Influences Brain Microvascular Heterogeneity: Relative Roles of Astrocytes and
Manjusha Thakar1, Midrelle E Noumbissi1,2, Monique F Stins1,3
1Malaria Research Institute, Department Molecular Microbiology & Immunology, Johns Hopkins School Public Health, Baltimore, MD 21205, USA.
Abstract:
Postmortem neuropathology shows clear regional differences in many brain diseases. For example, brains from cerebral malaria (CM) patients show more hemorrhagic punctae in the brain's white matter (WM) than grey matter (GM). The underlying reason for these differential pathologies is unknown. Here, we assessed the effect of the vascular microenvironment on brain endothelial phenotype, focusing endothelial protein C receptor (EPCR). We demonstrate that the basal level of EPCR expression in cerebral microvessels is heterogeneous in the WM compared to the GM. We used in vitro brain endothelial cell cultures and showed that the upregulation of EPCR expression was associated with exposure to oligodendrocyte conditioned media (OCM) compared to astrocyte conditioned media (ACM). Our findings shed light on the origin of the heterogeneity of molecular phenotypes at the microvascular level and might help better understand the variation in pathology seen in CM and other neuropathologies associated with vasculature in various brain regions.
Insights
Brain white matter endothelial cells show varied protein C receptor expression compared to grey matter. This difference, influenced by oligodendrocyte cells, may explain regional brain disease pathology.
Area of Science:
- Neuroscience
- Pathology
- Vascular Biology
Background:
- Neuropathology reveals distinct regional differences in brain diseases, such as cerebral malaria (CM).
- Cerebral malaria patients exhibit more hemorrhagic punctae in white matter (WM) than grey matter (GM), but the cause is unknown.
- Understanding regional vascular differences is crucial for comprehending varied neuropathologies.
Purpose of the Study:
- To investigate the impact of the vascular microenvironment on brain endothelial cell phenotype.
- To focus on the expression of endothelial protein C receptor (EPCR) and its regional heterogeneity.
- To explore the cellular and molecular basis for differential brain pathologies.
Main Methods:
- Assessed EPCR expression in postmortem brain tissue, comparing WM and GM microvessels.
- Utilized in vitro brain endothelial cell cultures.
- Exposed endothelial cells to oligodendrocyte conditioned media (OCM) and astrocyte conditioned media (ACM) to study EPCR regulation.
Main Results:
- Demonstrated heterogeneous basal EPCR expression in WM microvessels compared to GM.
- Showed that oligodendrocyte conditioned media (OCM) significantly upregulates EPCR expression in brain endothelial cells.
- Astrocyte conditioned media (ACM) did not induce the same level of EPCR upregulation.
Conclusions:
- The study identifies oligodendrocyte-derived factors as key regulators of EPCR expression in brain endothelium.
- Findings suggest that regional differences in the brain's vascular microenvironment, specifically EPCR levels, contribute to varied neuropathology.
- This research provides insights into the origins of molecular heterogeneity in brain microvessels and its role in diseases like CM.
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