Epilepsy is a chronic brain disease that affects approximately 65 million people worldwide. However, despite the continuous development of antiepileptic drugs, over 30% patients with epilepsy progress to drug-resistant epilepsy. For this reason, it is a high priority objective in preclinical research to find novel therapeutic targets and to develop effective drugs that prevent or reverse the molecular mechanisms underlying epilepsy progression. Among these potential therapeutic targets, we highlight currently available information involving signaling pathways (Wnt/β-catenin, Mammalian Target of Rapamycin (mTOR) signaling and zinc signaling), enzymes (carbonic anhydrase), proteins (erythropoietin, copine 6 and complement system), channels (Transient Receptor Potential Vanilloid Type 1 (TRPV1) channel) and receptors (galanin and melatonin receptors). All of them have demonstrated a certain degree of efficacy not only in controlling seizures but also in displaying neuroprotective activity and in modifying the progression of epilepsy. Although some research with these specific targets has been done in relation with epilepsy, they have not been fully explored as potential therapeutic targets that could help address the unsolved issue of drug-resistant epilepsy and develop new antiseizure therapies for the treatment of epilepsy.

Epilepsy is a common neurological disease characterized by recurrent unpredictable seizures. For the last 30 years, microdialysis sampling has been used to measure changes in excitatory and inhibitory neurotransmitter concentrations before, during, and after seizures. These advances have fostered breakthroughs in epilepsy research by identifying neurochemical changes associated with seizures and correlating them to electrophysiological data. Recent advances in methodology may be useful in further delineating the chemical underpinnings of seizures. A new model of ictogenesis has been developed that allows greater control over the timing of seizures that are similar to spontaneous seizures. This model will facilitate making chemical measurements before and during a seizure. Recent advancements in microdialysis sampling, including the use of segmented flow, "fast" liquid chromatography (LC), and capillary electrophoresis with laser induced fluorescence (CE-LIF) have significantly improved temporal resolution to better than 1-min, which could be used to measure transient, spontaneous neurochemical changes associated with seizures. Microfabricated sampling probes that are markedly smaller than conventional probes and allow for a much greater spatial resolution have been developed. They may allow the targeting of specific brain regions important to epilepsy studies. Coupling microdialysis sampling to optogenetics and light-stimulated release of neurotransmitters may also prove useful for studying epileptic seizures.

The use of Cannabis for medicinal purposes has been documented since ancient times, where one of its principal cannabinoids extracted from Cannabis sativa, cannabidiol (CBD), has emerged over the last few years as a promising molecule with anti-seizure potential. Here, we present an overview of recent literature pointing out CBD’s pharmacological profile (solubility, metabolism, drug-drug interactions, etc.,), CBD’s interactions with multiple molecular targets as well as advances in preclinical research concerning its anti-seizure effect on both acute seizure models and chronic models of epilepsy. We also highlight the recent attention that has been given to other natural cannabinoids and to synthetic derivatives of CBD as possible compounds with therapeutic anti-seizure potential. All the scientific research reviewed here encourages to continue to investigate the probable therapeutic efficacy of CBD and its related compounds not only in epilepsy but also and specially in drug-resistant epilepsy, since there is a dire need for new and effective drugs to treat this disease.

Introduction: Spontaneous ventriculomegaly has been observed in rats that were presumed normal. Because the external phenotype of these animals is unremarkable, they can be inadvertently included in behavioral experiments, despite the considerable enlargement of the ventricular system, reduced cortical thickness, and hippocampal atrophy upon imaging. Given the role of such structures in memory consolidation, we evaluated long‐term memory retention while decision making in rats with spontaneous ventriculomegaly.Methods: We studied adult male Sprague Dawley rats, identified as having spontaneous ventriculomegaly, while performing baseline magnetic resonance imaging scanning intended for a different research protocol. Control (n = 7) and experimental (n = 6) animals were submitted to a delayed‐alternation task (no delay, 30, 60, and 180 s) and an object‐in‐context recognition task. During the first task, we evaluated the number of correct choices as well as the latency to reach any of the cavities located at the end of each branch arm during each trial. The second task assessed the rodents’ ability to remember where they had previously encountered a specific object, calculating the context recognition index.Results: When compared to control animals, rats with spontaneous ventriculomegaly required significantly more training sessions to reach the 80% criterion during the training phase. Moreover, they showed reduced delayed‐alternation performance in the evaluated times, reaching significance only at 180 s. Increased latencies while trying to reach the cavity were also observed. Evaluation of the long‐term memory formation during the object‐in‐context recognition task showed that subjects with ventriculomegaly spent less time investigating the familiar object, resulting in a significantly decreased recognition index value.Conclusion: Our results are the first to show how spontaneous ventriculomegaly‐induced cerebral structural damage affects decision‐making behaviors, particularly when comparing between immediate and delayed trials. Moreover, this lesion disrupts the animals’ ability to recall or express contextual information.

Previously we demonstrated that noninvasive transcranial focal electrical stimulation (TFS) with sub-effective doses of diazepam reduces status epilepticus (SE)-induced neuronal damage. However, it was unclear if this neuroprotective effect is a consequence of the decrease in the glutamate release. The aim of the present study was to evaluate the effects of TFS on γ-Aminobutyric acid (GABA) and glutamate release in the hippocampus during pilocarpine-induced SE. After pilocarpine administration, the rats showed progressive behavioral changes that culminated in SE with a significant increase of GABA and glutamate (95 and 128% respectively), even more evident at the end of the experiment (120 and 182% respectively), 5 hours after pilocarpine injection and was associated with the prevalence of high-voltage rhythmic spikes and increased spectral power in the 4-90 Hz bands. The TFS application during the SE decreased the convulsive expression, the prevalence of high-voltage rhythmic spikes and spectral power in 4-8 Hz and 30-90 Hz bands. These effects were associated with lower release of GABA and glutamate in the hippocampus. These results support the anticonvulsive and neuroprotective effects induced by TFS.