Retinoic acid, a metabolite of vitamin A, acts through either genomic or nongenomic actions. The genomic action of retinoids exerts effects on gene transcription through interaction with retinoid receptors such as retinoic acid receptors (RARα, β, and γ) and retinoid X receptors (RXRα, β, and γ) that are primarily concentrated in amygdala, pre-frontal cortex, and hippocampal areas in the brain. In response to retinoid binding, RAR/RXR heterodimers undergo major conformational changes and orchestrate the transcription of specific gene networks. Previous experimental studies have reported that retinoic acid exerts an antiepileptogenic effect through diverse mechanisms, including the modulation of gap junctions, neurotransmitters, long-term potentiation, calcium channels and some genes. To our knowledge, there are no previous or current clinical trials evaluating the use of retinoic acid for seizure control.

Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid proliferation, invasiveness, therapeutic resistance, and an immunosuppressive tumor microenvironment. A subpopulation of glial stem-like cells (GSCs) within GBM tumors contributes significantly to tumor initiation, progression, and relapse, displaying remarkable adaptability to oxidative stress and metabolic reprogramming. Recent evidence implicates the atypical kinases RIOK1 and RIOK2 in promoting GBM growth and proliferation through their interaction with oncogenic pathways such as AKT and c-Myc. Concurrently, the redox-sensitive Nrf2/Keap1 axis regulates antioxidant defenses and supports GSC survival and chemoresistance. Additionally, aberrant activation of the canonical Wnt/β-catenin pathway in GSCs enhances their self-renewal, immune evasion, and resistance to standard therapies, particularly under oxidative stress conditions. This review integrates current knowledge on how redox homeostasis and key signaling pathways converge to sustain GSC maintenance and GBM malignancy. Finally, we discuss emerging redox-based therapeutic strategies designed to target GSC resilience, modulate the tumor immune microenvironment, and surmount treatment resistance.

Epilepsy is a neurological disorder that involves abnormal and recurrent neuronal discharges, producing epileptic seizures. Recently, it has been proposed that the Wnt signaling pathway is essential for central nervous system development and function because it modulates important processes such as hippocampal neurogenesis, synaptic clefting, and mitochondrial regulation. Wnt/β-catenin signaling regulates changes induced by epileptic seizures, including neuronal death. Several genetic studies associate Wnt/β-catenin signaling with neuronal excitability and epileptic activity. Mutations and chromosomal defects underlying syndromic or inherited epileptic seizures have been identified. However, genetic factors underlying the susceptibility of an individual to develop epileptic seizures have not been fully studied yet. In this review, we describe the genes involved in neuronal excitability in epileptogenic zones dependent on the Wnt/β-catenin pathway.

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Background: Epilepsy is a common neurological disorder characterized by abnormal and recurrent neuronal discharges that result in epileptic seizures. The dentate nuclei of the cerebellum receive excitatory input from different brain regions. Purkinje cell loss due to chronic seizures could lead to decreased inhibition of these excitatory neurons, resulting in the activation of apoptotic cascades in the dentate nucleus. Objective: The present study was designed to determine whether there is a presence of apoptosis (either intrinsic or extrinsic) in the dentate nucleus, the final relay of the cerebellar circuit, following kindling-induced seizures. Methods: In order to determine this, seizures were triggered via the amygdaloid kindling model. Following 0, 15, or 45 stimuli, rats were sacrificed, and the cerebellum was extracted. It was posteriorly prepared for the immunohistochemical analysis with cell death biomarkers: TUNEL, Bcl-2, truncated Bid (tBid), Bax, cytochrome C, and cleaved caspase 3 (active form). Our findings reproduce results obtained in other parts of the cerebellum. Results: We found a decrease of Bcl-2 expression, an anti-apoptotic protein, in the dentate nucleus of kindled rats. We also determined the presence of TUNEL-positive neurons, which confirms the presence of apoptosis in the dentate nucleus. We observed the expression of tBid, Bax, as well as cytochrome C and cleaved caspase-3, the main executor caspase of apoptosis. Conclusion: There is a clear activation of both the intrinsic and extrinsic apoptotic pathways in the cells of the dentate nucleus of the cerebellum of rats subjected to amygdaloid kindling.

Many neurotoxic substances produce toxic effects on the nervous system. Given the neurotoxic substances found in the human body, certain people have been regarded as having a propensity to epileptic seizures. In many situations, the neurotransmission processes of these toxins are similar to the physiopathology of epilepsy. Epileptic models have been developed to induce seizures in animals, allowing researchers to study convulsive seizure mechanisms. Pentylenetetrazol, kainic acid, pilocarpine, penicillin, aluminum, bicuculline, picrotoxine, 4-aminopyridine, strictine, domoic acid, and other compounds fall under this category. However, there are some drugs used in clinical practice that can cause neurotoxicity as well. In this chapter, the predominant substances and drugs involved in epileptogenesis through neurotoxicity effects are reviewed. Throughout this chapter, we attempt to describe the mechanisms documented in the literature, in which epileptic seizures cause neurotoxicity in the brain by themselves, as shown with excitotoxicity mediated by glutamate and ions involved.