Diisopropylfluorophosphate-induced status epilepticus drives complex glial cell phenotypes in adult male mice.

Organophosphate pesticides and nerve agents (OPs), are characterized by cholinesterase inhibition. In addition to severe peripheral symptoms, high doses of OPs can lead to seizures and status epilepticus (SE). Long lasting seizure activity and subsequent neurodegeneration promote neuroinflammation leading to profound pathological alterations of the brain.

Ketogenic diet and Neuroinflammation.

The high-fat, low-carbohydrate ketogenic diet (KD) is an established treatment for drug-resistant epilepsy with a proven efficacy. The KD is being explored for Febrile Infection-Related Epilepsy Syndrome (FIRES) and epileptic encephalopathies. There is growing evidence that KD works by targeting dysregulated adaptive and innate immunity that occurs in drug-resistant epilepsy and in refractory status epilepticus.

Characterization of organophosphate-induced brain injuries in a convulsive mouse model of diisopropylfluorophosphate exposure.

Organophosphate (OP) compounds constitute a class of highly toxic molecules, characterized by irreversible cholinesterase (ChE) inhibition. Being either pesticides or chemical warfare agents, they present a major health issue in some countries, as well as a terrorist or military threat. Prompted by the need for suitable animal models to test novel medical countermeasures, we developed a new convulsive mouse model of OP poisoning using diisopropylfluorophosphate (DFP).

Anti-ictogenic and antiepileptogenic properties of perampanel in mature and immature rats.

Objective: Perampanel (PER) is a selective noncompetitive antagonist at α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, the first of its class approved for the adjunctive treatment of partial onset seizures and generalized seizures. This study explored anti-ictogenic and antiepileptogenic effects of PER in rats at different stages of development.

Methods: Using a rapid kindling model in postnatal day 14 (P14), P21, P28, and P60 rats, we studied two doses of PER: 1 and 2 mg/kg injected intraperitoneally 30 min before afterdischarge assessment.

Different response to antiepileptic drugs according to the type of epileptic events in a neonatal ischemia-reperfusion model.

Perinatal arterial stroke is the most frequent form of cerebral infarction in children. Neonatal seizures are the most frequent symptom during the neonatal period. The current management of perinatal stroke is based on supportive care.

Pro-epileptogenic effects of viral-like inflammation in both mature and immature brains.

Background: Infectious encephalitides are most often associated with acute seizures during the infection period and are risk factors for the development of epilepsy at later times. Mechanisms of viral encephalitis-induced epileptogenesis are poorly understood. Here, we evaluated the contribution of viral encephalitis-associated inflammation to ictogenesis and epileptogenesis using a rapid kindling protocol in rats.

Ketogenic diet exhibits anti-inflammatory properties.

The ketogenic diet (KD) is an established treatment for refractory epilepsy, including some inflammation-induced epileptic encephalopathies. In a lipopolysaccharide (LPS)-induced fever model in rats, we found that animals given the KD for 14 days showed less fever and lower proinflammatory cytokine levels than control animals. However, KD rats exhibited a decrease in circulating levels of arachidonic acid and long-chain n-3 polyunsaturated fatty acids (PUFAs), suggesting that the anti-inflammatory effect of KD was probably not due to an increase in anti-inflammatory n-3 PUFA derivatives.

Anti-ictogenic and antiepileptogenic properties of brivaracetam in mature and immature rats.

Objective: Brivaracetam (BRV) is a new antiepileptic drug candidate rationally designed for high affinity and selectivity for the synaptic vesicle protein 2A. This study explored anti-ictogenic and antiepileptogenic effects of BRV in rats at different stages of development.

Methods: Using a rapid kindling model in P14, P21, P28, and P60 rats, we studied two doses of BRV: 10 and 100 mg/kg injected intraperitoneally 30 min before afterdischarge assessment.

Inflammation and epilepsy in the developing brain: clinical and experimental evidence.

There is an increasing evidence to support a role of inflammatory processes in epilepsy. However, most clinical and experimental studies have been conducted in adult patients or using adult rodents. The pediatric epilepsies constitute a varied group of diseases that are most frequently age specific.

Outcome of status epilepticus. What do we learn from animal data?

Status Epilepticus (SE) is a life-threatening neurologic disorder defined as 5 minutes or more of a continuous seizure. SE can represent an exacerbation of a preexisting seizure disorder, the initial manifestation of a seizure disorder, or an insult other than a seizure disorder. In humans, there are several differences between SE that occurs in adults and children.

Stiripentol exhibits higher anticonvulsant properties in the immature than in the mature rat brain.

Purpose: After the first positive experimental data in rodents in the early 1970s demonstrating the anticonvulsant effect of stiripentol (STP), in vitro studies showed that STP acts directly on γ-aminobutyric acid A (GABAA ) receptors. Chloride influx is higher when these receptors contain an α3 subunit, leading to the hypothesis that STP might exhibit higher efficacy in the immature brain.

Methods: We explored this issue by studying the efficacy of STP in P21 and P75 rats using the pentylenetetrazol model of acute seizures or the lithium-pilocarpine status epilepticus model.

A novel RAB33B mutation in Smith-McCort dysplasia.

Smith-McCort dysplasia (SMC) is a rare autosomal recessive spondylo-epi-metaphyseal dysplasia with skeletal features identical to those of Dyggve-Melchior-Clausen syndrome (DMC) but with normal intelligence and no microcephaly. Although both syndromes were shown to result from mutations in the DYM gene, which encodes the Golgi protein DYMECLIN, a few SMC patients remained negative in DYM mutation screening. Recently, autozygosity mapping and exome sequencing in a large SMC family have allowed the identification of a missense mutation in RAB33B, another Golgi protein involved in retrograde transport of Golgi vesicles.