Abstract
Unregulated neuro-inflammation mediates seizures in temporal lobe epilepsy (TLE). Our aim was to determine the effect of CD40–CD40L activation in experimental seizures. CD40 deficient mice (CD40KO) and control mice (wild type, WT) received pentenyltetrazole (PTZ) or pilocarpine to evaluate seizures and status epilepticus (SE) respectively. In mice, anti-CD40L antibody was administered intranasally before PTZ. Brain samples from human TLE and post-seizure mice were processed to determine CD40–CD40L expression using histological and molecular techniques. CD40 expression was higher in hippocampus from human TLE and in cortical neurons and hippocampal neural terminals after experimental seizures. CD40–CD40L levels increased after seizures in the hippocampus and in the cortex. After SE, CD40L/CD40 levels increased in cortex and showed an upward trend in the hippocampus. CD40KO mice demonstrated reduction in seizure severity and in latency compared to WT mice. Anti-CD40L antibody limited seizure susceptibility and seizure severity. CD40L–CD40 interaction can serve as a target for an immuno-therapy for TLE.
Highlights
Unregulated neuro-inflammation mediates seizures in temporal lobe epilepsy (TLE)
Since epilepsy research currently aims to understand the fundamental role of inflammation in seizure development, we studied the CD40L–CD40 activation in experimental seizures induced by pentylenetetrazol (PTZ) or pilocarpine in wild type (WT) and CD40 receptor-deficient adult mice (CD40KO) using animal models for translational clinical seizures
Using an immunohistological approach in hippocampal cryosections obtained from patients (n = 4) that underwent neurosurgical treatment for Temporal Lobe Epilepsy (TLE), the CD40 immunoreactivity (IR) was highly expressed in hippocampal regions (Fig. 1)
Summary
Unregulated neuro-inflammation mediates seizures in temporal lobe epilepsy (TLE). Our aim was to determine the effect of CD40–CD40L activation in experimental seizures. Most patients with TLE respond favorably to current anti-epileptic drugs (AED), almost 30% of TLE patients have limbic seizures that become refractory to medical treatments, requiring surgical resection of parts of the temporal lobe These patients have an increased risk of adverse drug reactions to AED, cognitive impairments, psychiatric comorbidities, or early m ortality[3,4]. Since epilepsy research currently aims to understand the fundamental role of inflammation in seizure development, we studied the CD40L–CD40 activation in experimental seizures induced by pentylenetetrazol (PTZ) or pilocarpine in wild type (WT) and CD40 receptor-deficient adult mice (CD40KO) using animal models for translational clinical seizures. We observed that CD40L–CD40 expression increased in the brain after seizures
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