Some reports have described that a high fructose diet is associated with a deficit of hippocampus-dependent cognitive functions. In this study, we have evaluated the effects of fructose on spatial memory and molecular markers in the hippocampus and prefrontal cortex and analyzed whether those alterations are reversible. Male Wistar rats (n = 60) began their treatment during adolescence. A group was forced to drink a solution of 10% fructose for twelve weeks. Another group was subjected to the same fructose intake schedule, but later fructose was removed, and tap water was provided for four weeks. After treatments, spatial memory was evaluated with Barnes maze. Different neurogenesis, inflammation, astrocyte, and energy homeostasis markers were evaluated with immunofluorescence, ELISA, and Western blot. Changes were analyzed using two-way repeated-measures ANOVA, one-way ANOVA, and Tukeýs posthoc test (p < 0.05). Results showed that after long-term consumption of fructose, there was an impairment of spatial memory. This deficit was concomitant with the abolition of hippocampal neurogenesis and significant increases of IL-1b in the hippocampus and prefrontal cortex. Levels of COX-2 were decreased in the hippocampus. Besides, fructose induced a significant increase in GFAP and a decrease of glutamine synthetase. Likewise, energy homeostasis-associated neuropeptide orexin-A and their receptors (ORX R1 and ORX R2) were significantly increased. The spatial memory deficit, neuroinflammation, and changes in some proteinś expression were permanent one month after the fructose elimination from the diet. These results suggest that fructose induces substantial hippocampal and cortical changes, and those are irreversible after a shift in the diet.

Biological treatments involve the application of metallic material coatings to enhance biocompatibility and properties. In invasive therapies, metallic electrodes are utilized, which are implanted in patients. One of these invasive therapeutic procedures is deep brain stimulation (DBS), an effective therapy for addressing the motor disorders observed in patients with Parkinson’s disease (PD). This therapy involves the implantation of electrodes (IEs) into the subthalamic nucleus (STN). However, there is still a need for the optimization of these electrodes. Plasma-synthesized polypyrrole doped with iodine (PPPy/I) has been reported as a biocompatible and anti-inflammatory biomaterial that promotes nervous system regeneration. Given this information, the objective of the present study was to develop and characterize a PPPy/I-coated electrode for implantation into the STN. The characterization results indicate a uniform coating along the electrode, and physical–chemical characterization studies were conducted on the polymer. Subsequently, the IEs, both coated and uncoated with PPPy/I, were implanted into the STN of male rats of the Wistar strain to conduct an electrographic recording (EG-R) study. The results demonstrate that the IE coated with PPPy/I exhibited superior power and frequency signals over time compared to the uncoated IE (p < 0.05). Based on these findings, we conclude that an IE coated with PPPy/I has optimized functional performance, with enhanced integrity and superior signal quality compared to an uncoated IE. Therefore, we consider this a promising technological development that could significantly improve functional outcomes for patients undergoing invasive brain therapies.

It has been proposed that interictal epileptiform discharges observed in epilepsy-related structures, such as the hippocampus contributes to epileptogenesis. Intermittent fasting (IF) produces anticonvulsant effects protecting against experimentally induced seizures. It has been suggested that protective effects could be associated with astrocytic metabolic changes. However, it is unknown whether IF modifies the epileptogenic process. Therefore, this work aimed to analyze the impact of IF on interictal epileptiform discharges in the rat hippocampus and their possible correlation with astrocytic activation. Male Wistar rats were divided into two groups: one group had free access to food, while the other group was subjected to IF (food was provided for 2 h a day). Both groups underwent a hippocampal electrical kindling protocol with 36 stimulations. Our results showed that IF inhibited the incidence of generalized seizures induced by kindling and significantly reduced the total spectral power of interictal epileptiform discharges in the hippocampus. Furthermore, IF prevented the rise in fasting blood glucose and reduced seizure-induced astrogliosis by preventing the GFAP expression and the morphological complexity of astrocytes in the hippocampal CA3 region. These results support the notion that IF modifies epileptogenesis by modulating hippocampal hyperexcitability during the interictal stage, which could be associated with reductions in glucose metabolism and astrogliosis. Graphical Abstract

Gliomas, including glioblastomas (GB) and high-grade astrocytomas (HGA), are the most common brain tumors in adults, with poor survival rates around 15 months. Hormonal factors, particularly progesterone receptor (PR) activation, promote tumor growth. Current treatment involves surgery, radiotherapy and chemotherapy (temozolomide), but survival rates remain low. Repurposing mifepristone (MF), a contraceptive drug, shows promise for GB treatment, warranting further study. PR expression in U87, U251 and C6 cell lines were assessed using immunofluorescence and Western Blot. PR isoforms were quantified by densitometry. Progesterone (P4) and 5α-dihydroprogesterone (5α-DHP) synthesis were evaluated using LC/MS. MF's effect on cell viability was determined by IC₅₀ and IC₂₀ values. Its impact on non-tumoral cells and 3D glioma sphere formation was also analyzed. The effects of in situ administration of MF were assessed in vivo using a rat model with C6 glioma implants. Clinical outcomes were evaluated in GB patients receiving MF alongside standard treatment. PR was predominantly nuclear in all cell lines, with U87 showing the highest PR-B isoform levels. Only U251 synthesized 5α-DHP significantly. MF reduced viability in U251, U87 and C6 cells without affecting non-tumoral cells. Sphere formation efficiency decreased with MF treatment. In rats, MF reduced tumor volume dose-dependently. Clinically, MF improved patient survival from 165 to 588days and enhanced quality of life without severe adverse effects. MF effectively reduces GB cell viability, sphere formation efficacy and tumor volume. These findings support further investigation of MF as a therapeutic strategy in GB treatment. Our research highlights the critical role PR in GB progression using in vitro and in vivo models. MF, a PR modulator, effectively reduced cell viability and sphere formation in cellular assays and significantly decreased tumor volume in an in vivo study. The pilot trial demonstrated the pharmacological safety of using MF as an adjuvant in GB treatment. Patients treated with MF showed a significant increase in survival, with an 80% survival rate at 1 year compared to 0% in those who were treated with the standard treatment.

El cannabidiol (CBD), uno de los principales componentes de la planta Cannabis sativa, tiene propiedades farmacológicas con potencial terapéutico, por lo que ha sido objeto de estudio en los últimos años. Al momento, sólo ha sido aprobado legalmente para el tratamiento de las convulsiones farmacorresistentes en pacientes pediátricos. Los avances realizados en la investigación de las acciones terapéuticas del CBD en epilepsia, se han sustentado principalmente en el empleo de modelos animales. Con estos modelos animales se han evaluado un amplio rango de dosis, con diversas vías y esquemas de administración. A nivel clínico, se han evaluado las interacciones farmacocinéticas/farmacodinámicas entre el CBD y otros fármacos antiepilépticos, a fin de establecer su utilidad como coadyuvante, realizando ajustes de dosis y valorando la presencia de efectos adversos (como la inducción enzimática en el hígado). Además, el CBD es una molécula que interactúa con múltiples blancos moleculares y que además posee propiedades antioxidantes y antiinflamatorias intrínsecas. Esta información nos ha demostrado que los efectos anticonvulsivantes del CBD aún no han sido explorados a detalle en el tratamiento de la epilepsia farmacorresistente, donde las opciones terapéuticas son limitadas. Tampoco se han evaluado los mecanismos moleculares involucrados en sus efectos anticonvulsivos, donde la administración intracerebral del CBD podría facilitar esta tarea. Con el desarrollo de esta revisión, esperamos que el lector tenga una visión general del estado actual del CBD como una molécula con potencial terapéutico para el tratamiento no solo de la epilepsia sino también de la epilepsia farmacorresistente.