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Resolution Of Central Nervous System Astrocytic And Endothelial Sources Of Ccl2 Gene Expression During Evolving Neuroinflammation, Bandana Shrestha, Shujun Ge, Joel S. Pachter

UCHC Articles - Research

Background

The chemokine CCL2 is a critical mediator of neuroinflammation in diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). CCL2 drives mononuclear cell infiltration into the central nervous system (CNS), alters expression and distribution of microvascular endothelial tight junction proteins, and disrupts the blood–brain and blood-spinal cord barriers. Immunohistochemistry has consistently revealed astrocytes to be a source of this chemokine during neuroinflammation, while providing less uniform evidence that CNS endothelial cells may also express CCL2. Moreover, the relative contributions of these cell types to the CNS pool of CCL2 during MS/EAE are unclear and …

Cell-Selective Knockout And 3d Confocal Image Analysis Reveals Separate Roles For Astrocyte- And Endothelial-Derived Ccl2 In Neuroinflammation, Debayon Paul, Shujun Ge, Yen Lemire, Evan R. Jellison, David R. Serwanski, Joel S. Pachter

UCHC Articles - Research

Background

Expression of chemokine CCL2 in the normal central nervous system (CNS) is nearly undetectable, but is significantly upregulated and drives neuroinflammation during experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis which is considered a contributing factor in the human disease. As astrocytes and brain microvascular endothelial cells (BMEC) forming the blood–brain barrier (BBB) are sources of CCL2 in EAE and other neuroinflammatory conditions, it is unclear if one or both CCL2 pools are critical to disease and by what mechanism(s).

Methods

Mice with selective CCL2 gene knockout (KO) in astrocytes (Astro KO) or …