Chemokines and chemokine receptors in CNS pathology

Głąbiński, Andrzej; Ransohoff, R. M.

doi:10.3109/13550289909029740

Cited by 170 publications

(94 citation statements)

References 76 publications

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“…The protective action of reparixin demonstrates the pathogenic role of inflammation induced by chemokines, particularly PMN chemoattractants acting on CXCR1/2, in cerebral ischemia (27,28). This is in agreement with the notion that PMN infiltration is important in post-ischemic damage in the brain as suggested by several studies using anti-leukocyte strategies in experimental stroke (2).…”

Section: Discussionsupporting

confidence: 77%

The Interleukin-8 (IL-8/CXCL8) Receptor Inhibitor Reparixin Improves Neurological Deficits and Reduces Long-term Inflammation in Permanent and Transient Cerebral Ischemia in Rats

Villa

Triulzi

Cavalieri

et al. 2007

Mol Med

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Leukocyte infiltration is viewed as a pharmacological target in cerebral ischemia. We previously reported that reparixin, a CXCL8 receptor blocker that inhibits neutrophil infiltration, and related molecules can reduce infarct size in a rat model of transient middle cerebral artery occlusion (MCAO). The study aims were to compare the effects of reparixin in transient and permanent MCAO using varied treatment schedules and therapeutic windows to evaluate effects on long-term neurological deficits and late inflammatory response. Reparixin, administered for 1 to 3 days, 3.5 to 6 h after MCAO, ameliorates neurological function recovery and inhibits long-term inflammation. The infarct size reduction at 24 h, evaluated by TTC staining, is more pronounced in transient MCAO. MRI analysis identified a decrease in the progression of infarct size by reparixin that was more evident at 48 h in permanent MCAO, and was associated with a significantly improved recovery from long-term neurological deficits.

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Section: Discussionsupporting

confidence: 77%

The Interleukin-8 (IL-8/CXCL8) Receptor Inhibitor Reparixin Improves Neurological Deficits and Reduces Long-term Inflammation in Permanent and Transient Cerebral Ischemia in Rats

Villa

Triulzi

Cavalieri

et al. 2007

Mol Med

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“…CCL2 (MCP-1) and its receptor CCR2 are involved in CNS pathologies such as multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) 67 , CNS trauma 68 and are known as mediators of leukocyte migration into the CNS under neuroinflammatory conditions 69,70 In vitro BBB models have to be seen as autonomous systems, isolated from body regulation, but still endowed with major in vivo properties and a potential for regulation by environmental cues. No "ideal" in vitro BBB model has been proposed yet 71,72,73 because the endothelial cell monolayers lack a number of important constituents of the neuro-glia vascular unit (NGVU) and are isolated from blood and body regulation.…”

Section: Molecular and Functional Characterizationmentioning

confidence: 99%

Setting-up an <em>In Vitro</em> Model of Rat Blood-brain Barrier (BBB): A Focus on BBB Impermeability and Receptor-mediated Transport

Molino¹,

Jabès²,

Lacassagne

et al. 2014

JoVE

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Citation: Molino, Y., Jabès, F., Lacassagne, E., Gaudin, N., Khrestchatisky, M. Setting-up an In Vitro Model of Rat Blood-brain Barrier (BBB): A Focus on BBB Impermeability and Receptor-mediated Transport. J. Vis. Exp. (88), e51278, doi:10.3791/51278 (2014). AbstractThe blood brain barrier (BBB) specifically regulates molecular and cellular flux between the blood and the nervous tissue. Our aim was to develop and characterize a highly reproducible rat syngeneic in vitro model of the BBB using co-cultures of primary rat brain endothelial cells (RBEC) and astrocytes to study receptors involved in transcytosis across the endothelial cell monolayer. Astrocytes were isolated by mechanical dissection following trypsin digestion and were frozen for later co-culture. RBEC were isolated from 5-week-old rat cortices. The brains were cleaned of meninges and white matter, and mechanically dissociated following enzymatic digestion. Thereafter, the tissue homogenate was centrifuged in bovine serum albumin to separate vessel fragments from nervous tissue. The vessel fragments underwent a second enzymatic digestion to free endothelial cells from their extracellular matrix. The remaining contaminating cells such as pericytes were further eliminated by plating the microvessel fragments in puromycin-containing medium. They were then passaged onto filters for co-culture with astrocytes grown on the bottom of the wells. RBEC expressed high levels of tight junction (TJ) proteins such as occludin, claudin-5 and ZO-1 with a typical localization at the cell borders. The transendothelial electrical resistance (TEER) of brain endothelial monolayers, indicating the tightness of TJs reached 300 ohm·cm 2 on average. The endothelial permeability coefficients (Pe) for lucifer yellow (LY) was highly reproducible with an average of 0.26 ± 0.11 x 10 -3 cm/min. Brain endothelial cells organized in monolayers expressed the efflux transporter P-glycoprotein (P-gp), showed a polarized transport of rhodamine 123, a ligand for P-gp, and showed specific transport of transferrin-Cy3 and DiILDL across the endothelial cell monolayer. In conclusion, we provide a protocol for setting up an in vitro BBB model that is highly reproducible due to the quality assurance methods, and that is suitable for research on BBB transporters and receptors.

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“…Chemokines, together with proinflammatory cytokines, have been proposed to play a decisive role in leukocyte attachment to the blood-brain barrier endothelium. Furthermore, chemokines have been recognized as the key mediators of cerebral leukocyte extravasation and accumulation (3,28,64). Chemokines are low-molecularweight chemoattractant peptides that are divided into four subfamilies, termed CXC (␣), CC (␤), C (␥), and CX 3 C (␦), primarily based on the position of the first two N-terminal conserved cysteine residues but also based on functional and genetic similarities (5,6,55,65).…”

mentioning

confidence: 99%

Chemokine Gene Expression in Astrocytes of Borna Disease Virus-Infected Rats and Mice in the Absence of Inflammation

Sauder

Hallensleben

Pagenstecher

et al. 2000

J Virol

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Borna disease virus (BDV) causes CD8؉ T-cell-mediated meningoencephalitis in immunocompetent mice and rats, thus providing a valuable animal model for studying the mechanisms of virus-induced central nervous system (CNS) immunopathology. Chemokine-mediated leukocyte recruitment to the CNS is a crucial step in the development of neurological disease. We found increased mRNA levels of IP-10 and other chemokines in brains of adult rats following infection with BDV. The marked increase in chemokine gene expression at about day 8 postinfection seemed to immediately precede the inflammatory process. In brains of rats infected as newborns, in which inflammation was only mild and transient, sustained expression of IP-10 and RANTES genes was observed. In situ hybridization studies revealed that astrocytes were the major source of IP-10 mRNAs in brains of rats infected as newborns and as adults. In brains of infected mice lacking CD8 ؉ T cells (␤2m 0/0 ), transcripts encoding IP-10 and RANTES were also observed. IP-10 transcripts were also present in a small number of scattered astrocytes of infected knockout mice lacking mature B and T cells as well as functional alpha/beta and gamma interferon receptors, indicating that BDV can induce chemokine synthesis in the absence of interferons and other B-or T-cell-derived cytokines. These data provide strong evidence that CNS-resident cells are involved in the early localized host immune response to infection with BDV and support the concept that chemokines are pivotal for the initiation of virus-induced CNS inflammation.

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Chemokines and chemokine receptors in CNS pathology

Cited by 170 publications

References 76 publications

The Interleukin-8 (IL-8/CXCL8) Receptor Inhibitor Reparixin Improves Neurological Deficits and Reduces Long-term Inflammation in Permanent and Transient Cerebral Ischemia in Rats

The Interleukin-8 (IL-8/CXCL8) Receptor Inhibitor Reparixin Improves Neurological Deficits and Reduces Long-term Inflammation in Permanent and Transient Cerebral Ischemia in Rats

Setting-up an <em>In Vitro</em> Model of Rat Blood-brain Barrier (BBB): A Focus on BBB Impermeability and Receptor-mediated Transport

Chemokine Gene Expression in Astrocytes of Borna Disease Virus-Infected Rats and Mice in the Absence of Inflammation

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