ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Astrocytic dysfunction in epileptogenesis: consequence of altered potassium and glutamate homeostasis?
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.
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Who cites it
155 citing papers in PubMed, 343 citations in OpenAlex.
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- Dynamic modulation of the blood-brain barrier in the healthy brain.Nature reviews. Neuroscience · 2025Review
- Collapsing Perisomatic Inhibition Leads to Epileptic Fast-Ripple Oscillations Caused by Pseudosynchronous Firing of CA3 Pyramidal Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Liver X Receptor Beta Regulates Glial Dynamics and Cortical Network Remodeling in a Freezing Lesion-Cortical Dysplasia Model.CNS neuroscience & therapeutics · 2025Article
- Heart-brain axis, gliotransmitters and peripheral neurogenesis: Emerging regenerative roles of cardiac nexus glia in health and disease.World journal of cardiology · 2025Review
- Blood‑brain barrier dysfunction in epilepsy: Mechanisms, therapeutic strategies and future orientation (Review).International journal of molecular medicine · 2025Review
- Transcriptome Derived Artificial neural networks predict PRRC2A as a potent biomarker for epilepsy.Journal, genetic engineering & biotechnology · 2025Article
- Interplay of Neuroinflammation and Epilepsy in Glioblastoma Multiforme: Mechanisms and Therapeutic Implications.Journal of molecular neuroscience : MN · 2025Review
- Glutamate, a Key for Astrocytes to Participate in Brain Function and Diseases.Neurochemical research · 2025Review
- Astrocytic NHERF-1 Increases Seizure Susceptibility by Inhibiting Surface Expression of TREK-1.Glia · 2025Article
- Glutamate uptake is transiently compromised in the perilesional cortex following controlled cortical impact.Cerebral cortex (New York, N.Y. : 1991) · 2025Article
- Alpha-Pinene Decreases the Elevated Levels of Astrogliosis, Pyroptosis, and Autophagy Markers in the Hippocampus Triggered by Kainate in a Rat Model of Temporal Lobe Epilepsy.Molecular neurobiology · 2025Article
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- Regulation of Glutamate Transporter Type 1 by TSA and the Antiepileptic Mechanism of TSA.Neurochemical research · 2025Article
- Imaging blood-brain barrier dysfunction in drug-resistant epilepsy: A multi-center feasibility study.Epilepsia · 2025Article
- Astroglia's role in synchronized spontaneous neuronal activity: from physiology to pathology.Frontiers in cellular neuroscience · 2025Review
- Helminthic larval stage induces cellular apoptosis via caspase 9-mediated mitochondrial dysfunction.Frontiers in immunology · 2025Article
- RhoA/ROCK2 signaling pathway regulates Mn-induced alterations in tight junction proteins leading to cognitive dysfunction in mice.Current research in toxicology · 2025Article
95 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
Abstract
Focal epilepsy often develops following traumatic, ischemic, or infectious brain injury. While the electrical activity of the epileptic brain is well characterized, the mechanisms underlying epileptogenesis are poorly understood. We have recently shown that in the rat neocortex, long-lasting breakdown of the blood-brain barrier (BBB) or direct exposure of the neocortex to serum-derived albumin leads to rapid upregulation of the astrocytic marker GFAP (glial fibrillary acidic protein), followed by delayed (within 4-7 d) development of an epileptic focus. We investigated the role of astrocytes in epileptogenesis in the BBB-breakdown and albumin models of epileptogenesis. We found similar, robust changes in astrocytic gene expression in the neocortex within hours following treatment with deoxycholic acid (BBB breakdown) or albumin. These changes predict reduced clearance capacity for both extracellular glutamate and potassium. Electrophysiological recordings in vitro confirmed the reduced clearance of activity-dependent accumulation of both potassium and glutamate 24 h following exposure to albumin. We used a NEURON model to simulate the consequences of reduced astrocytic uptake of potassium and glutamate on EPSPs. The model predicted that the accumulation of glutamate is associated with frequency-dependent (>100 Hz) decreased facilitation of EPSPs, while potassium accumulation leads to frequency-dependent (10-50 Hz) and NMDA-dependent synaptic facilitation. In vitro electrophysiological recordings during epileptogenesis confirmed frequency-dependent synaptic facilitation leading to seizure-like activity. Our data indicate a transcription-mediated astrocytic transformation early during epileptogenesis. We suggest that the resulting reduction in the clearance of extracellular potassium underlies frequency-dependent neuronal hyperexcitability and network synchronization.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.