Inhibition of 2-AG hydrolysis differentially regulates blood brain barrier permeability after injury

Journal of Neuroinflammation
Justin R PiroTarek A Samad

Abstract

Acute neurological insults caused by infection, systemic inflammation, ischemia, or traumatic injury are often associated with breakdown of the blood-brain barrier (BBB) followed by infiltration of peripheral immune cells, cytotoxic proteins, and water. BBB breakdown and extravasation of these peripheral components into the brain parenchyma result in inflammation, oxidative stress, edema, excitotoxicity, and neurodegeneration. These downstream consequences of BBB dysfunction can drive pathophysiological processes and play a substantial role in the morbidity and mortality of acute and chronic neurological insults, and contribute to long-term sequelae. Preserving or rescuing BBB integrity and homeostasis therefore represents a translational research area of high therapeutic potential. Induction of general and localized BBB disruption in mice was carried out using systemic administration of LPS and focal photothrombotic ischemic insult, respectively, in the presence and absence of the monoacylglycerol lipase (MAGL) inhibitor, CPD-4645. The effects of CPD-4645 treatment were assessed by gene expression analysis performed on neurovascular-enriched brain fractions, cytokine and inflammatory mediator measurement, and functional assess...Continue Reading

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Citations

Aug 2, 2019·Stroke; a Journal of Cerebral Circulation·Sang-Ho ChoiAfonso C Silva
Dec 14, 2018·Cellular and Molecular Life Sciences : CMLS·Roberto VillaseñorLudovic Collin
Jan 1, 2021·CNS Neuroscience & Therapeutics·Xiaowen HuangJunlei Chang
Apr 13, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Katja SchmitzIrmgard Tegeder
Jun 3, 2021·International Journal of Molecular Sciences·Ludmila A KasatkinaEva M Sturm

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Methods Mentioned

BETA
ELISA
protein assay
RNA-seq
transgenic

Software Mentioned

quantMode
R
lmFit
DAVID
ImageJ
limma
Bioconductor
GENCODE
edgeR package
Image Studio

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