Unraveling the neuroprotective effect of perampanel and lacosamide combination in the corneal kindling model for epilepsy in mice.

Background: Scientific evidence to guide clinicians on the use of different antiseizure drugs in combination therapy is either very limited or lacking. In this study, the impact of lacosamide and perampanel alone and in combination was tested in corneal kindling model in mice, which is a cost-effective mechanism for screening of antiseizure drugs.

Methods: The impact of lacosamide (5 mg/kg) and perampanel (0.

ECM stiffness regulates lung fibroblast survival through RasGRF1 dependent signaling.

Extracellular matrix stiffness is one of the multiple mechanical signals that alters cellular behavior. During studies exploring the effect of matrix rigidity on lung fibroblast survival we discovered that enhanced survival on stiff substrates is dependent on elevated Ras activity, owing to the activation of the GEF, RasGRF1. Mechanistically, we found that the increased Ras activity lead to the activation of both the AKT and ERK pathways.

Co-administration of coenzyme Q10 and curcumin mitigates cognitive deficits and exerts neuroprotective effects in aluminum chloride-induced Alzheimer's disease in aged mice.

Aluminum chloride (AlCl), a known neurotoxic and Alzheimerogenic metal disrupts redox homeostasis which plays a pivotal role in pathophysiology of neurodegenerative disorders, particularly cognitive decline. The current study was designed to unveil the long-term neuroprotective outcomes and efficacy of CoQ10 and curcumin low dose (100 mg/kg each) combination in 18-months old geriatric male Balb/c mice subjected to AlCl-prompted memory derangements (200 mg/kg in water bottles) for 28 days. The neuroprotective properties driven by antioxidant mechanisms were assessed via observing cellular pathology in key-memory related brain regions including the cornuammonis (CA3 and DG) and cortex 2/3 layer.

Probiotics by Modulating Gut-Brain Axis Together With Brivaracetam Mitigate Seizure Progression, Behavioral Incongruities, and Prevented Neurodegeneration in Pentylenetetrazole-Kindled Mice.

Background: The microbiota-gut-brain axis (MGBA) is a central nexus that integrates higher cognitive and emotional centers of the central nervous system (CNS) within the intricate functioning of the intestine. Accumulating evidence suggests that dysbiosis in the taxonomic diversity of gut flora plays a salient role in the progression of epilepsy and comorbid secondary complications.

Methods: In the current study, we investigated the impact of long-term oral bacteriotherapy (probiotics; 10 mL/kg; 10 colony-forming unit/ml) as an adjunctive treatment intervention with brivaracetam (BRV; 10 mg/kg) over 21 days on pentylenetetrazole (PTZ) induced augmented epileptic response and associated electrographical and behavioral perturbations in mice.

Brivaracetam and rufinamide combination increased seizure threshold and improved neurobehavioral deficits in corneal kindling model of epilepsy.

Background: Besides seizures, a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy, which further debilitates their quality of life. This study provides an in-depth characterization of the impact of brivaracetam and rufinamide individually and in combination at 10 and 20 mg/kg doses, respectively, on corneal kindling-induced generalized seizures and behavioral alterations. Furthermore, observed convulsive frequency and behavioral changes were correlated to post-kindling-induced changes in the activity of markers of oxidative stress.

Neuroprotective potential of topiramate, pregabalin and lacosamide combination in a rat model of acute SE and intractable epilepsy: Perspectives from electroencephalographic, neurobehavioral and regional degenerative analysis.

The lithium-pilocarpine model is commonly used to recapitulate characteristics of human intractable focal epilepsy. In the current study, we explored the impact of topiramate (TPM) alone and in combination with pregabalin and lacosamide administration for 6 weeks on the evolution of spontaneous recurrent seizures (SRS) and disease-modifying potential on associated neuropsychiatric comorbidities. In addition, redox impairments and neurodegeneration in hippocampus regions vulnerable to temporal lobe epilepsy (TLE) were assessed by cresyl violet staining.

Neuroprotective Effect of Brivaracetam and Perampanel Combination on Electrographic Seizures and Behavior Anomalies in Pentylenetetrazole-Kindled Mice.

Pentylenetetrazole (PTZ)-induced kindling is a broadly used experimental model to study the anticonvulsive potential of new and existing chemical moieties with the aim of discovering drugs hindering seizure progression and associated neurological comorbidities. In the present study, the impact of brivaracetam (BRV) (10 and 20 mg/kg) as monotherapy as well as in combination with 0.25 mg/kg of perampanel (PRP) was investigated on seizure progression with simultaneous electroencephalographic changes in PTZ kindling mouse model.

Ameliorative effect of Nyctanthes arbor-tristis L. by suppression of pentylenetetrazole-induced kindling in mice: An insight from EEG, neurobehavioral and in-silico studies.

Epilepsy is an abiding condition associated with recurrent seizure attacks along with associated neurological and psychological emanation owing to disparity of excitatory and inhibitory neurotransmission. The current study encompasses the assessment of the Nyctanthes arbor-tristis L. methanolic extract (Na.

Optogenetically controlled inflammasome activation demonstrates two phases of cell swelling during pyroptosis.

Inflammasomes are multiprotein platforms that control caspase-1 activation, which process the inactive precursor forms of the inflammatory cytokines IL-1β and IL-18, leading to an inflammatory type of programmed cell death called pyroptosis. Studying inflammasome-driven processes, such as pyroptosis-induced cell swelling, under controlled conditions remains challenging because the signals that activate pyroptosis also stimulate other signaling pathways. We designed an optogenetic approach using a photo-oligomerizable inflammasome core adapter protein, apoptosis-associated speck-like containing a caspase recruitment domain (ASC), to temporally and quantitatively manipulate inflammasome activation.

Perampanel increases seizure threshold in pentylenetetrazole-kindled mice and improves behavioral dysfunctions by modifying mRNA expression levels of BDNF/TrkB and inflammatory markers.

Perampanel (PER), a novel 3rd-generation antiseizure drug that modulates altered post-synaptic glutamatergic storming by selectively inhibiting AMPA receptors, is recently approved to treat intractable forms of seizures. However, to date, presumably consequences of long-term PER therapy on the comorbid deleterious psychiatric disturbances and its correlation with neuroinflammatory parameters are not fully investigated in chronic models of epilepsy. Therefore, we investigated the real-time effect of PER on brain electroencephalographic (EEG) activity, behavioral alterations, redox balance, and relative mRNA expression in pentylenetetrazole (PTZ) induced kindling.

Unveiling the potential of perampanel and pregabalin in addressing pentylenetetrazole-induced electrographic alterations and neurobehavioral anomalies.

Chemical kindling is broadly used experimental model to investigate novel treatments on the process of epileptogenesis and coexisting behavioral comorbidities. The current study aimed to investigate the low dose perampanel (PER) (0.125 and 0.

Demaghi, a polyherbal formulation, mitigates aluminum chloride-induced neurological impairment in mice: Insights from phytochemical analysis and behavioral assessment.

Herbal products have been very popular in Pakistan for their curative significance against various disorders. Demaghi (DEMG) is a widely used herbal product claimed to own natural substances having neuroprotective potential. The current study aims to scientifically validate the chemical composition as well as its neuroprotective claims of this widely used herbal tonic.

Mitigation of behavioral deficits and cognitive impairment by antioxidant and neuromodulatory potential of in D-galactose treated rats.

Plants and their parts have been extensively used for the therapeutic purposes such as aging due to their powerful antioxidative belongings. Presently, we intended to examine the consequence of fruit peel of (M.M) on D-galactose (D-Gal) persuaded anxiety and/or depression profile, cognition and serotonin metabolism in rats.

Effects of long-term extract supplementation on fear, cognition and brain antioxidant levels.

Introduction: is an indigenous plant known for various remedial properties. The present study aimed to evaluate the neuroprotective potential of methanolic extract (AA) bark as current scientific trend is searching plant for neurodegenerative diseases, worldwide.

Methodology: In experiments, the AA was analyzed for phenols, flavonoids, antioxidative and cholinesterase inhibitory properties with subsequent detailed characterization for secondary metabolites.

Tiagabine suppresses pentylenetetrazole-induced seizures in mice and improves behavioral and cognitive parameters by modulating BDNF/TrkB expression and neuroinflammatory markers.

Tiagabine (Tia), a new-generation antiseizure drug that mimics the GABAergic signaling by inhibiting GABA transporter type-1, is the least studied molecule in chronic epilepsy models with comorbid neurobehavioral and neuroinflammatory parameters. Therefore, the current study investigated the effects of Tia in a real-time manner on electroencephalographic (EEG) activity, behavioral manifestations and mRNA expression in pentylenetetrazole (PTZ)-kindled mice. Male BALB/c mice were treated with tiagabine (0.

HSF1-Activated Non-Coding Stress Response: Satellite lncRNAs and Beyond, an Emerging Story with a Complex Scenario.

In eukaryotes, the heat shock response is orchestrated by a transcription factor named Heat Shock Factor 1 (HSF1). HSF1 is mostly characterized for its role in activating the expression of a repertoire of protein-coding genes, including the heat shock protein (HSP) genes. Remarkably, a growing set of reports indicate that, upon heat shock, HSF1 also targets various non-coding regions of the genome.

Short- and Mid-Term Outcomes of Endovascular Stenting for the Treatment of Post-Thrombotic Syndrome due to Iliofemoral and Caval Occlusive Disease: A Multi-Centric Study from the French Society of Diagnostic and Interventional Cardiovascular Imaging (SFICV).

Purpose: To assess the results of endovascular treatment in a large population of patients suffering from post-thrombotic syndrome (PTS) due to iliocaval occlusive disease.

Methods: In this retrospective multi-center study, 698 patients treated by stenting for PTS in 15 French centers were analyzed. Primary, primary assisted, and secondary patency rates were assessed, and clinical efficacy was evaluated using Villalta and Chronic Venous Insufficiency Questionnaire in 20 questions (CIVIQ-20) scores.

A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model.

The purpose of this study is to use a multi-technique approach to detect the effects of spatially fractionated X-ray Microbeam (MRT) and Minibeam Radiation Therapy (MB) and to compare them to seamless Broad Beam (BB) irradiation. Healthy- and Glioblastoma (GBM)-bearing male Fischer rats were irradiated in-vivo on the right brain hemisphere with MRT, MB and BB delivering three different doses for each irradiation geometry. Brains were analyzed post mortem by multi-scale X-ray Phase Contrast Imaging-Computed Tomography (XPCI-CT), histology, immunohistochemistry, X-ray Fluorescence (XRF), Small- and Wide-Angle X-ray Scattering (SAXS/WAXS).

Haploinsufficiency of ARFGEF1 is associated with developmental delay, intellectual disability, and epilepsy with variable expressivity.

Purpose: ADP ribosylation factor guanine nucleotide exchange factors (ARFGEFs) are a family of proteins implicated in cellular trafficking between the Golgi apparatus and the plasma membrane through vesicle formation. Among them is ARFGEF1/BIG1, a protein involved in axon elongation, neurite development, and polarization processes. ARFGEF1 has been previously suggested as a candidate gene for different types of epilepsies, although its implication in human disease has not been well characterized.