ArticleStem cell research & therapy2024
Cell-specific extracellular vesicle-encapsulated exogenous GABA controls seizures in epilepsy.
Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 35 citations in OpenAlex.
- Stem cell-based therapeutics in epilepsy: current advances and future prospects.Stem cells translational medicine · 2026Review
- A systematic safety assessment of zuranolone: real-world adverse event analysis from the FAERS database.Archives of women's mental health · 2026Article
- Pharmacological inhibition of RE1 silencing transcription factor disrupts SOX2 expression and neurogenesis in human induced pluripotent stem cells derived neuronal models.Metabolic brain disease · 2025Article
- The Role of Extracellular Vesicles in Neuropsychiatric Disorders.Advanced pharmaceutical bulletin · 2025Review
- Targeting GABA signaling in type 1 diabetes and its complications- an update on the state of the art.Pharmacological reports : PR · 2025Review
- Potential of extracellular vesicle cargo as molecular signals in Schizophrenia: a scoping review.Schizophrenia (Heidelberg, Germany) · 2025Review
- Host-membrane lipid composition controlsFrontiers in immunology · 2025Article
- Single-cell, single-nucleus and xenium-based spatial transcriptomics analyses reveal inflammatory activation and altered cell interactions in the hippocampus in mice with temporal lobe epilepsy.Biomarker research · 2024Article
- MISEV2023 provides an updated and key reference for researchers studying the basic biology and applications of extracellular vesicles.Stem cells translational medicine · 2024Article
- Extracellular vesicle therapy in neurological disorders.Journal of biomedical science · 2024Review
- Cell and molecular targeted therapies for diabetic retinopathy.Frontiers in endocrinology · 2024Review
- Geraniol Ameliorates Pentylenetetrazol-Induced Epilepsy, Neuroinflammation, and Oxidative Stress via Modulating the GABAergic Tract: In vitro and in vivo studies.Drug design, development and therapy · 2024Article
- Anticonvulsant role of nitric oxide synthase inhibitors in epilepsy (Review).Medicine internationalReview
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEpilepsy affects ∼60 million people worldwide. Most antiseizure medications in the market act on voltage-gated sodium or calcium channels, indirectly modulating neurotransmitter GABA or glutamate levels or multiple targets. Earlier studies made significant efforts to directly deliver GABA into the brain with varied success. Herein, we have hypothesized to directly deliver exogenous GABA to the brain with epilepsy through extracellular vesicles (EVs) from human GABA-producing cells and their progenitors as EVs largely mimic their parent cell composition.
methodsHuman neural stem cells (NSCs), medial ganglionic eminence (MGE) cells, and GABAergic interneurons (INs) were generated from induced pluripotent stem cells (iPSCs) and characterized. EVs were isolated from NSCs, MGE cells, and INs and characterized for size and distribution, morphological features, and molecular markers. Exogenous GABA was passively loaded to the isolated EVs as a zwitterion at physiological pH, and the encapsulated dose of GABA was quantified. Epilepsy was developed through status epilepticus induction in Fisher rats by administration of repeated low doses of kainic acid. The extent of the seizures was measured for 10 h/ day for 3-6 months by video recording and its evaluation for stage III, IV and V seizures as per Racine scale. EVs from INs, MGE cells, and NSCs encapsulated with exogenous GABA were sequentially tested in the 4
resultsExogenic GABA could enter the brain through EVs. Treatment with EVs from INs and MGE cells encapsulated with GABA significantly reduced total seizures, stage V seizures, and total time spent in seizure activity. EVs from NSCs encapsulated with GABA demonstrated limited seizure control. Exogenic GABA alone and EVs from INs and MGE cells individually failed to control seizures. Further, exogenic GABA with EVs from MGE cells improved depressive behavior while partially improving memory functions. Co-localization studies confirmed exogenous GABA with presynaptic vesicles in the hippocampus, indicating the interaction of exogenous GABA in the brain with epilepsy.
conclusionFor the first time, the study demonstrated that exogenous GABA could be delivered to the brain through brain cell-derived EVs, which could regulate seizures in temporal lobe epilepsy. It is identified that the cellular origin of EVs plays a vital role in seizure control with exogenous GABA.
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