The Chemokine CCL2 Mediates the Seizure-enhancing Effects of Systemic Inflammation.
Chiara CerriSacha GenovesiManuela AllegraFrancesco PistilloUrsula PüntenerAngelo GuglielmottiV Hugh PerryYuri BozziMatteo CaleoPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2016)
Substantial evidence points to a role for inflammation in epilepsy, but currently there is little insight as to how inflammatory pathways impact on seizure generation. Here, we examine the molecular mediators linking peripheral inflammation with seizure susceptibility in mice with mesial temporal lobe epilepsy. We show that a systemic inflammatory challenge via lipopolysaccharide administration potently enhances seizure frequency and upregulates the expression of the chemokine CCL2. Remarkably, selective pharmacological interference with CCL2 or its receptor CCR2 suppresses lipopolysaccharide-induced seizure enhancement. Thus, CCL2/CCR2 signaling plays a key role in linking systemic inflammation with seizure susceptibility.
Keyphrases
- temporal lobe epilepsy
- lipopolysaccharide induced
- oxidative stress
- inflammatory response
- liver injury
- liver fibrosis
- drug induced
- dendritic cells
- poor prognosis
- toll like receptor
- signaling pathway
- metabolic syndrome
- adipose tissue
- skeletal muscle
- lps induced
- high fat diet induced
- insulin resistance
- chemotherapy induced