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Purpose: Temporal lobe epilepsy is associated with the inflammatory process related to the basic mechanisms that lead to seizure susceptibility and brain damage. Platelet‐activating factor (PAF), a potent, short‐lived phospholipid mediator of inflammation, participates in physiologic signaling in the brain. However, after seizures, PAF accumulates in the brain and activates intracellular signaling...
PurposeThe chemokine fractalkine/CX3CL1 and its receptor CX3CR1 are widely expressed in the central nervous system (CNS). Recent evidence showed that CX3CL1 participates in inflammatory responses that are common features of CNS disorders, such as epilepsy. Mesial temporal lobe epilepsy (MTLE) is the prevalent form of focal epilepsy in adults, and hippocampal sclerosis (HS) represents the most common...
Patients who have sustained brain injury or had developmental brain lesions present a non‐negligible risk for developing delayed epilepsy. Finding therapeutic strategies to prevent development of epilepsy in at‐risk patients represents a crucial medical challenge. Noncoding microRNA molecules (miRNAs) are promising candidates in this area. Indeed, deregulation of diverse brain‐specific miRNAs has...
Objective
Epilepsy affects 60 million people worldwide. Despite the development of antiepileptic drugs, up to 35% of patients are drug refractory with uncontrollable seizures. Toll‐like receptors (TLRs) are central components of the nonspecific innate inflammatory response. Because TLR3 was recently implicated in neuronal plasticity, we hypothesized that it may contribute to the development of epilepsy...
This study aimed to determine the role C5aR1 plays in mediating immune responses acutely after pilocarpine‐induced status epilepticus (SE), specifically those of brain‐infiltrating leukocytes. Three days following pilocarpine SE, we determined by flow cytometry the brain immune cell phenotypes and measured key proinflammatory and antiinflammatory cytokine expression by infiltrating leukocytes and...
This study examined whether Toll‐like receptors 2 (TLR2) contribute to rapid kindling epileptogenesis. A TLR2 agonist, lipoteichoic acid (LTA), LTA antibody (LTA‐A), or normal saline (control) was administered daily over 3 consecutive days, unilaterally into ventral hippocampus of adult male Wistar rats. Thirty minutes after the last injection, the animals were subjected to a rapid kindling procedure...
Objective
Status epilepticus (SE) is a life‐threatening and commonly drug‐refractory condition. Novel therapies are needed to rapidly terminate seizures to prevent mortality and morbidity. Monoacylglycerol lipase (MAGL) is the key enzyme responsible for the hydrolysis of the endocannabinoid 2‐arachidonoylglycerol (2‐AG) and a major contributor to the brain pool of arachidonic acid (AA). Inhibiting...
Objective
Accumulating evidence suggests that brain inflammation, elicited by epileptogenic insults, is involved in epilepsy development. Noninvasive nuclear imaging of brain inflammation in animal models of epileptogenesis represents a diagnostic in vivo approach with potential for direct translation into the clinic. Here, we investigated up‐regulation of the translocator protein (TSPO) indicative...
Objective
Mesiotemporal lobe epilepsy is the most common type of drug‐resistant partial epilepsy, with a specific history that often begins with status epilepticus due to various neurological insults followed by a silent period. During this period, before the first seizure occurs, a specific lesion develops, described as unilateral hippocampal sclerosis (HS). It is still challenging to determine...
Owing to the complexity of the pathophysiological mechanisms driving epileptogenesis following traumatic brain injury (TBI), effective preventive treatment approaches are not yet available for posttraumatic epilepsy (PTE). Neuroinflammation appears to play a critical role in the pathogenesis of the acquired epilepsies, including PTE, but despite a large preclinical literature demonstrating the ability...
Epilepsy is a common neurological disorder that increases the risk of morbidity and mortality. Autoimmune epilepsy is a subset of epilepsy that occurs in the setting of autoimmunity, such as in autoimmune encephalitis (AIE). AIE is an autoimmune disorder characterized by immune‐mediated neuroinflammation resulting in a variety of neurological symptoms, including psychiatric disturbance, cognitive...
Objective
Neuroinflammation is a major theme in epilepsy, which has been characterized in acquired epilepsy but is poorly understood in genetic epilepsy. γ‐Aminobutyric acid type A receptor subunit gene mutations are significant causes of epilepsy, and we have studied the pathophysiology directly resulting from defective receptor channels. Here, we determined the proinflammatory factors in a genetic...
Objective
Neuroinflammation associated with anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis may facilitate seizures. We previously showed that intraventricular administration of cerebrospinal fluid from patients with anti‐NMDAR encephalitis to mice precipitates seizures, thereby confirming that antibodies are directly pathogenic. To determine whether interleukin (IL)‐1‐mediated inflammation...
Objective
Medial temporal lobe epilepsy (MTLE) is a drug‐resistant focal epilepsy that can be caused by a broad spectrum of different inciting events, including tumors, febrile seizures, and viral infections. In human epilepsy surgical resections as well as in animal models, an involvement of the adaptive immune system was observed. We here analyzed the presence of T cells in various subgroups of...
Alzheimer's disease (AD) can increase the risk of epilepsy by up to 10‐fold compared to healthy age‐matched controls. However, the pathological mechanisms that underlie this increased risk are poorly understood. Because disruption in brain glutamate homeostasis has been implicated in both AD and epilepsy, this might play a mechanistic role in the pathogenesis of epilepsy in AD. Prior to the formation...
Objective
Effective treatment for the prevention of posttraumatic epilepsy is still not available. Here, we sought to determine whether blocking receptor for advanced glycation end products (RAGE) or toll‐like receptor 4 (TLR4) signaling pathways would prevent posttraumatic epileptogenesis.
Methods
In a mouse undercut model of posttraumatic epilepsy, daily injections of saline, RAGE monoclonal...
Currently no sensitive and specific biomarkers exist to predict drug‐resistant epilepsy. We determined whether blood levels of high‐mobility group box 1 (HMGB1), a mediator of neuroinflammation implicated in drug‐resistant epilepsies, identifies patients with drug‐resistant seizures. Patients with drug‐resistant epilepsy express significantly higher levels of blood HMGB1 than those with drug‐responsive,...
Objective
Although epilepsies and neurodegenerative disorders show pathophysiological similarities, their direct functional associations are unclear. Here, we tested the hypothesis that experimental seizures can induce tau hyperphosphorylation and amyloidogenic modifications over time, with intersections with neuroinflammation.
Methods
We used a model of mesial temporal lobe epilepsy (MTLE) where...
Objective
We previously demonstrated that interleukin‐1 receptor‐mediated immune activation contributes to seizure severity and memory loss in anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis. In the present study, we assessed the role of the myeloid differentiation primary response gene 88 (MyD88), an adaptor protein in Toll‐like receptor signaling, in the key phenotypic characteristics of...
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