DNA Cell Biol 2016 Jun 11;35(6):257-60. Epub 2016 May 11.

2 Neuroscience Institute , National Research Council (CNR), Pisa, Italy .

Epilepsy is a chronic disorder characterized by spontaneous recurrent seizures. Several lines of evidence demonstrate that inflammatory processes within the brain parenchyma contribute to recurrence and precipitation of seizures. In both epileptic patients and animal models, seizures upregulate inflammatory mediators, which in turn may enhance brain excitability. We recently showed that the C-C motif ligand 2 (CCL2) chemokine (also known as monocyte chemoattractant protein-1 [MCP-1]) mediates the seizure-promoting effects of inflammation. Systemic inflammatory challenge in chronically epileptic mice markedly enhanced seizure frequency and upregulated CCL2 expression in the brain. Selective pharmacological blockade of CCL2 synthesis or C-C chemokine receptor type 2 (CCR2) significantly suppressed inflammation-induced seizures. These results have important implications for the development of novel anticonvulsant therapies: drugs interfering with CCL2 signaling are used clinically for several human disorders and might be redirected for use in pharmacoresistant epilepsy. Here we review the role of CCL2/CCR2 signaling in linking systemic inflammation with seizure susceptibility and discuss some open questions that arise from our recent studies.

J Neurosci 2016 Mar;36(13):3777-88

Neuroscience Institute, National Research Council, 56124 Pisa, Italy,

Unlabelled: Epilepsy is a chronic disorder characterized by spontaneous recurrent seizures. Brain inflammation is increasingly recognized as a critical factor for seizure precipitation, but the molecular mediators of such proconvulsant effects are only partly understood. The chemokine CCL2 is one of the most elevated inflammatory mediators in patients with pharmacoresistent epilepsy, but its contribution to seizure generation remains unexplored. Read More

J Neuroinflammation 2014 Jul 28;11:132. Epub 2014 Jul 28.

Université de Nice Sophia Antipolis, Nice 06103, France.

Background: Genetic and environmental factors are critical elements influencing the etiology of major depression. It is now accepted that neuroinflammatory processes play a major role in neuropsychological disorders. Neuroinflammation results from the dysregulation of the synthesis and/or release of pro- and anti-inflammatory cytokines with central or peripheral origin after various insults. Read More

J Neurosci 2017 Aug 17;37(33):7878-7892. Epub 2017 Jul 17.

Department of Cell Biology and Neuroscience, School of Arts and Sciences, Rutgers University, Piscataway, New Jersey 08854, and

Elevated levels of chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 have been reported in patients with temporal lobe epilepsy and in experimental seizures. However, the functional significance and molecular mechanism underlying CCL2-CCR2 signaling in epileptic brain remains largely unknown. In this study, we found that the upregulated CCL2 was mainly expressed in hippocampal neurons and activated microglia from mice 1 d after kainic acid (KA)-induced seizures. Read More

Expert Opin Investig Drugs 2011 Jun 6;20(6):745-56. Epub 2011 Apr 6.

Medical College of Korea University, Ansan Hospital, Division of Nephrology, Department of Internal Medicine, Ansan City, Korea.

Introduction: C-C chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1, and its receptor, C-C chemokine receptor 2 (CCR2), play important roles in various inflammatory diseases. Recently, it has been reported that the CCL2/CCR2 pathway also has an important role in the pathogenesis of metabolic syndrome through its association with obesity and related systemic complications.

Areas Covered: This review focuses on the roles of CCR2 in the pathogenesis of adipose tissue inflammation and other organ damage associated with metabolic syndrome, which is still a matter of debate in many studies. Read More