1,721,022 research outputs found
Epilepsy, Seizures, and Inflammation: Role of the C-C Motif Ligand 2 Chemokine
No full textEpilepsy 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
Autism with epilepsy: a clinical and genetic study. Research Protocol
No full textAbstract: Autism spectrum disorder (ASD) is a common neurodevelopmental condition affecting
~1% of people worldwide. Core ASD features present with impaired social communication abilities,
repetitive and stereotyped behaviors, and atypical sensory responses and are often associated with a
series of comorbidities. Among these, epilepsy is frequently observed. The co-occurrence of ASD
and epilepsy is currently thought to result from common abnormal neurodevelopmental pathways,
including an imbalanced excitation/inhibition ratio. However, the pathological mechanisms involved
in ASD-epilepsy co-morbidity are still largely unknown. Here, we propose a research protocol aiming
to investigate electrophysiological and genetic features in subjects with ASD and epilepsy. This study
will include a detailed electroencephalographic (EEG) and blood transcriptomic characterization of
subjects with ASD with and without epilepsy. The combined approach of EEG and transcriptomic
studies in the same subjects will contribute to a novel stratification paradigm of the heterogeneous
ASD population based on quantitative gene expression and neurophysiological biomarkers. In
addition, our protocol has the potential to indicate new therapeutic options, thus amending the
current condition of absence of data and guidelines for the treatment of ASD with epileps
Editorial: autism Spectrum disorders: developmental trajectories, Neurobiological Basis, treatment Update
Full text linkChemokines as new inflammatory players in the pathogenesis of epilepsy
No full textA large series of clinical and experimental studies supports a link between inflammation and epilepsy, indicating that inflammatory processes within the brain are important contributors to seizure recurrence and precipitation. Systemic inflammation can precipitate seizures in children suffering from epileptic encephalopathies, and hallmarks of a chronic inflammatory state have been found in patients with temporal lobe epilepsy. Research performed on animal models of epilepsy further corroborates the idea that seizures upregulate inflammatory mediators, which in turn may enhance brain excitability and neuronal degeneration. Several inflammatory molecules and their signaling pathways have been implicated in epilepsy. Among these, the chemokine pathway has increasingly gained attention. Chemokines are small cytokines secreted by blood cells, which act as chemoattractants for leukocyte migration. Recent studies indicate that chemokines and their receptors are also produced by brain cells, and are involved in various neurological disorders including epilepsy. In this review, we will focus on a subset of pro-inflammatory chemokines (namely CCL2, CCL3, CCL5, CX3CL1) and their receptors, and their increasingly recognized role in seizure control
Editorial: Autism Spectrum Disorders: Developmental Trajectories, Neurobiological Basis, Treatment Update, Volume 2
Full text linkIntrahippocampal infusion of botulinum neurotoxin E (BoNT/E) reduces spontaneous recurrent seizures in a mouse model of mesial temporal lobe epilepsy
No full textAutism Spectrum Disorders: developmental trajectories, neuobiological basis, treatment outcome
No full text
Botulinum neurotoxin E (Bont/E) reduces Ca1 neuron loss and granule cell dispersion, with no effects on chronic seizures, in a mouse model of temporal lobe epilepsy
No full textMesial temporal lobe epilepsy (MTLE) is often the result of an early insult that induces a reorganization in hippocampal circuitry leading, after a latent period, to chronic epilepsy. Hippocampal rearrangements during the latent phase include neuronal loss, axonal and dendritic plasticity, neurogenesis, and cell repositioning, but the role of these changes in epilepsy development is unclear. Here we have tested whether administration of the synaptic blocker botulinum neurotoxin E (BoNT/E) interferes with development of spontaneous seizures and histopathological changes following an episode of status epilepticus (SE). SE was induced by unilateral intrahippocampal injection of kainic acid in mice and BoNT/E was delivered to the same hippocampus 3 h later. We found that treatment with BoNT/E prolonged the duration of the latent period but did not block the occurrence of spontaneous seizures. At the histopathological level, BoNT/E reduced loss of CA1 pyramidal neurons and dispersion of den..
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