ArticleBrain : a journal of neurology2009
The cortical innate immune response increases local neuronal excitability leading to seizures.
Article in Brain : a journal of neurology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 163 citations in OpenAlex.
- Prolonged systemic inflammation worsens impairments to astrocyte CaAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Tri-Culture System Reveals an Activation Cascade From Microglia Through Astrocytes to Neurons During Neuroinflammation.Journal of neurochemistry · 2026Article
- Microglia-to-neuron signaling linksProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Microglia-to-neuron signaling increases lipid droplet metabolism, enhancing neuronal network activity.bioRxiv : the preprint server for biology · 2025Article
- Cerebrospinal fluid and serum cytokine profiles in severe viral encephalitis with implications for refractory status epilepticus: a retrospective observational study.Frontiers in immunology · 2025Observational
- PPARβ/δ Agonist GW0742 Modulates Microglial and Astroglial Gene Expression in a Rat Model of Temporal Lobe Epilepsy.International journal of molecular sciences · 2024Article
- Putative Role of Adenosine A1 Receptors in Exogenous Ketone Supplements-Evoked Anti-Epileptic Effect.International journal of molecular sciences · 2024Review
- Cell-specific IL-1R1 regulates the regional heterogeneity of microglial displacement of GABAergic synapses and motor learning ability.Cellular and molecular life sciences : CMLS · 2024Article
- The Emerging Role of Toll-Like Receptor-Mediated Neuroinflammatory Signals in Psychiatric Disorders and Acquired Epilepsy.Molecular neurobiology · 2024Review
- Therapeutic modulation of JAK-STAT, mTOR, and PPAR-γ signaling in neurological dysfunctions.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Long-term neuropsychological outcomes in children with febrile infection-related epilepsy syndrome (FIRES) treated with anakinra.Frontiers in neurology · 2023Article
- Opioids, microglia, and temporal lobe epilepsy.Frontiers in neurology · 2023Review
- Single-cell RNA-seq analyses inform necroptosis-associated myeloid lineages influence the immune landscape of pancreas cancer.Frontiers in immunology · 2023Article
- Microglia Remodelling and Neuroinflammation Parallel Neuronal Hyperactivation Following Acute Organophosphate Poisoning.International journal of molecular sciences · 2022Article
- Sepsis modulates cortical excitability and alters the local and systemic hemodynamic response to seizures.Scientific reports · 2022Article
- Neuronal hyperexcitability in Alzheimer's disease: what are the drivers behind this aberrant phenotype?Translational psychiatry · 2022Review
- Immunity, Ion Channels and Epilepsy.International journal of molecular sciences · 2022Review
- [European journal of nuclear medicine and molecular imaging · 2022Article
- Neuroinflammation and Proinflammatory Cytokines in Epileptogenesis.Molecular neurobiology · 2022Review
- An ultra-long new onset refractory status epilepticus: Winning the battle but losing the war?Epilepsy & behavior reports · 2022Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Brain glial cells, five times more prevalent than neurons, have recently received attention for their potential involvement in epileptic seizures. Microglia and astrocytes, associated with inflammatory innate immune responses, are responsible for surveillance of brain damage that frequently results in seizures. Thus, an intriguing suggestion has been put forward that seizures may be facilitated and perhaps triggered by brain immune responses. Indeed, recent evidence strongly implicates innate immune responses in lowering seizure threshold in experimental models of epilepsy, yet, there is no proof that they can play an independent role in initiating seizures in vivo. Here, we show that cortical innate immune responses alone produce profound increases of brain excitability resulting in focal seizures. We found that cortical application of lipopolysaccharide, binding to toll-like receptor 4 (TLR4), triples evoked field potential amplitudes and produces focal epileptiform discharges. These effects are prevented by pre-application of interleukin-1 receptor antagonist. Our results demonstrate how the innate immune response may participate in acute seizures, increasing neuronal excitability through interleukin-1 release in response to TLR4 detection of the danger signals associated with infections of the central nervous system and with brain injury. These results suggest an important role of innate immunity in epileptogenesis and focus on glial inhibition, through pharmacological blockade of TLR4 and the pro-inflammatory mediators released by activated glia, in the study and treatment of seizure disorders in humans.
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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.