Epilepsy is one of the most common chronic neurological disorders. Furthermore, it is associated to diminished health-related quality of life and is thus considered a major public health problem. In spite of the large number of available and ongoing development of several new antiepileptic drugs (AEDs), a high percentage of patients with epilepsy (35-40%) are resistant to pharmacotherapy. A hypothesis to explain pharmacoresistance in epilepsy suggests that overexpression of multidrug resistance proteins, such as P-glycoprotein, on the endothelium of the blood brain barrier represents a challenge for effective AED delivery and concentration levels in the brain. Proven therapeutic strategies to control pharmacoresistant epilepsy include epilepsy surgery and neuromodulation. Unfortunately, not all patients are candidates for these therapies. Nanotechnology represents an attractive strategy to overcome the limited brain access of AEDs in patients with pharmacoresistant epilepsy. This manuscript presents a review of evidences supporting this idea.
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http://dx.doi.org/10.2741/709 | DOI Listing |
Adv Sci (Weinh)
January 2025
McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, H3A 2B4, Canada.
Excitation-inhibition (E/I) imbalance is theorized as a key mechanism in the pathophysiology of epilepsy, with ample research focusing on elucidating its cellular manifestations. However, few studies investigate E/I imbalance at the macroscale, whole-brain level, and its microcircuit-level mechanisms and clinical significance remain incompletely understood. Here, the Hurst exponent, an index of the E/I ratio, is computed from resting-state fMRI time series, and microcircuit parameters are simulated using biophysical models.
View Article and Find Full Text PDFIntroduction: Hereditary bleeding disorders stem from the absence or insufficient levels of particular clotting proteins, essential for facilitating coagulation in the clotting cascade. Among the most prevalent are hemophilia A (deficiency of Factor VIII), hemophilia B (deficiency of Factor IX), and von Willebrand disease. Management of pharmacoresistant epilepsy is more difficult in a patient with bleeding disorder due to increased risk of bleeding during surgery.
View Article and Find Full Text PDFJ Cancer Res Clin Oncol
December 2024
Department of Neurosurgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Purpose: Analysis of autofluorescence holds promise for brain tumor delineation and diagnosis. Therefore, we investigated the potential of a commercial confocal laser scanning endomicroscopy (CLE) system for clinical imaging of brain tumors.
Methods: A clinical CLE system with fiber probe and 488 nm laser excitation was used to acquire images of tissue autofluorescence.
ACS Pharmacol Transl Sci
December 2024
Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia.
Epilepsy affects more than 70 million individuals of all ages worldwide and remains one of the most severe chronic noncommunicable neurological diseases globally. Several neurotransmitters, membrane protein channels, receptors, enzymes, and, more recently noted, various pathways, such as inflammatory and mTORC complexes, play significant roles in the initiation and propagation of seizures. Over the past two decades, significant developments have been made in the diagnosis and treatment of epilepsy.
View Article and Find Full Text PDFMolecules
November 2024
Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare, serious, and pharmacoresistant epileptic disorder often linked to gain-of-function mutations in the gene. encodes the sodium-activated potassium channel known as SLACK, making small molecule inhibitors of SLACK channels a compelling approach to the treatment of EIMFS and other epilepsies associated with mutations. In this manuscript, we describe a hit optimization effort executed within a series of 2-aryloxy--(pyrimidin-5-yl)acetamides that were identified via a high-throughput screen.
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