Improving the efficiency of antiseizure medication entering the brain is the key to reducing its peripheral toxicity. A combination of intranasal administration and nanomedicine presents a practical approach for treating epileptic seizures via bypassing the blood-brain barrier. In this study, phenytoin (PHT) loaded layered double hydroxide nanoparticles (BSA-LDHs-PHT) were fabricated via a coprecipitation - hydrothermal method for epileptic seizure control. In this study, we expound on the preparation method and characterization of BSA-LDHs-PHT. In-vitro drug release experiment shows both rapid and continuous drug release from BSA-LDHs-PHT, which is crucial for acute seizure control and chronic epilepsy therapy. In-vivo biodistribution assays after intranasal administration indicate excellent brain targeting ability of BSA-LDHs. Compared to BSA-Cyanine5.5, BSA-LDHs-Cyanine5.5 were associated with a higher brain/peripheral ratio across all tested time points. Following intranasal delivery with small doses of BSA-LDHs-PHT, the latency of seizures in the pentylenetetrazole-induced mouse models was effectively improved. Collectively, the present study successfully designed and applied BSA-LDHs-PHT as a promising strategy for treating epileptic seizures with an enhanced therapeutic effect.
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http://dx.doi.org/10.1186/s12951-024-02405-8 | DOI Listing |
Sci Rep
December 2024
Developmental Neurosciences, Great Ormond Street Institute of Child Health, University College London, London, UK.
Network hypersynchrony is emerging as an important system-level mechanism underlying seizures, as well as cognitive and behavioural impairments, in children with structural brain abnormalities. We investigated patterns of single neuron action potential behaviour in 206 neurons recorded from tubers, transmantle tails of tubers and normal looking cortex in 3 children with tuberous sclerosis. The patterns of neuronal firing on a neuron-by-neuron (autocorrelation) basis did not reveal any differences as a function of anatomy.
View Article and Find Full Text PDFAnn Clin Transl Neurol
December 2024
Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P. R. China.
Background: Variants in the GABRA2 gene, which encodes the α2 subunit of the γ-aminobutyric acid A receptor, have been linked to a rare form of developmental and epileptic encephalopathy (DEE) referred to as DEE78. Only eight patients have been reported globally. This study presents the clinical presentation and genetic analysis of a Chinese family with a child diagnosed with DEE78, due to a novel GABRA2 variant.
View Article and Find Full Text PDFAnn Clin Transl Neurol
December 2024
Department of Neurology, Movement Disorders Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Autosomal-dominant variants in the CPT1C gene have been associated with hereditary spastic paraplegia type 73 (SPG73), which typically presents with slowly progressive lower limb weakness and spasticity and is therefore considered a pure form of hereditary spastic paraplegia. However, we report two unrelated males with novel CPT1C variants (NM_001199753.2: patient 1: c.
View Article and Find Full Text PDFEpilepsia
December 2024
Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
Objective: The 5xFAD mouse model of Alzheimer disease (AD) recapitulates amyloid-beta (Aβ) deposition and pronounced seizure susceptibility observed in patients with AD. Forty-hertz audiovisual stimulation is a noninvasive technique that entrains gamma neural oscillations and can reduce Aβ pathology and modulate glial expression in AD models. We hypothesized that 40-Hz sensory stimulation would improve seizure susceptibility in 5xFAD mice and this would be associated with reduction of plaques and modulation of glial phenotypes.
View Article and Find Full Text PDFNeurol Neurochir Pol
December 2024
Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland.
Introduction And State Of The Art: Systemic lupus erythematosus (SLE) is an autoimmune disease that affects many organs throughout its course, most frequently the joints, skin and kidneys. Both the central (CNS) and peripheral (PNS) nervous systems are also often affected. T he involvement of the CNS has a negative prognosis in lupus patients.
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