ArticleJournal of neuroinflammation2021
IL-1β and HMGB1 are anti-neurogenic to endogenous neural stem cells in the sclerotic epileptic human hippocampus.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Advancing the Paradigm of Temporal Lobe Epilepsy as a Network Disease: The Promise of Biomarkers and Targeted Disease Modification.International journal of molecular sciences · 2026Review
- Anti-Inflammatory and Antioxidant Strategies in Epilepsy: From Molecular Mechanisms to Threshold Management.International journal of molecular sciences · 2026Review
- Restoring Septohippocampal Cholinergic Signaling Rescues Surgery-Induced Neurogenesis and Memory Deficits in Aged Mice.Aging cell · 2026Article
- Therapeutic mechanisms of umbilical cord mesenchymal stem cell-derived exosomes in ischemic stroke: A transcriptomic and metabolomic study.Neural regeneration research · 2026Article
- Current review on inducible nitric oxide synthase and Src tyrosine kinase inhibitors as disease-modifiers in preclinical models of epilepsy.Histology and histopathology · 2026Review
- Innate immune signalling, neuroinflammation and network plasticity in temporal lobe epilepsy.Frontiers in pharmacology · 2026Review
- Engram cell vulnerability in neurodegeneration: from mechanistic insights to therapeutic horizons.Frontiers in aging neuroscience · 2026Review
- Gut microbiota-neuroinflammation axis: A new mechanism and therapeutic target for comorbid depression in epilepsy.Brain, behavior, & immunity - health · 2025Review
- Triptolide Inhibits Epileptic Seizures by Rescuing the Neuroinflammation-Related GABAergic Dysfunction in Mice.CNS neuroscience & therapeutics · 2025Article
- Costunolide normalizes neuroinflammation and improves neurogenesis deficits in a mouse model of depression through inhibiting microglial Akt/mTOR/NF-κB pathway.Acta pharmacologica Sinica · 2025Article
- HMGB1 blood levels and neurological outcomes after traumatic brain injury: Insights from an exploratory study.Epilepsia open · 2025Article
- Research progress on the role of inflammatory mediators in the pathogenesis of epilepsy.Ibrain · 2025Review
- Increased expression of NLRP3 associated with elevated levels of HMGB1 in children with febrile seizures: a case-control study.BMC pediatrics · 2024Article
- The Role of Histone Deacetylases in NLRP3 Inflammasomesmediated Epilepsy.Current molecular medicine · 2024Review
- Impact of Vitamin D and IL-1β on Quality of Life in Pediatric Drug-Resistant Epilepsy.Journal of multidisciplinary healthcare · 2024Article
- Toll-like receptors as a missing link in Notch signaling cascade during neurodevelopment.Frontiers in molecular neuroscience · 2024Article
- Connexin 43 Promotes Neurogenesis via Regulating Aquaporin-4 after Cerebral Ischemia.Neurotoxicity research · 2023Article
- A high-density 3-dimensional culture model of human glioblastoma for rapid screening of therapeutic resistance.Biochemical pharmacology · 2023Article
- Interactions between astrocytes and extracellular matrix structures contribute to neuroinflammation-associated epilepsy pathology.Frontiers in molecular medicine · 2023Review
- Cuproptosis-related genes signature and validation of differential expression and the potential targeting drugs in temporal lobe epilepsy.Frontiers in pharmacology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe dentate gyrus exhibits life-long neurogenesis of granule-cell neurons, supporting hippocampal dependent learning and memory. Both temporal lobe epilepsy patients and animal models frequently have hippocampal-dependent learning and memory difficulties and show evidence of reduced neurogenesis. Animal and human temporal lobe epilepsy studies have also shown strong innate immune system activation, which in animal models reduces hippocampal neurogenesis. We sought to determine if and how neuroinflammation signals reduced neurogenesis in the epileptic human hippocampus and its potential reversibility.
methodsWe isolated endogenous neural stem cells from surgically resected hippocampal tissue in 15 patients with unilateral hippocampal sclerosis. We examined resultant neurogenesis after growing them either as neurospheres in an ideal environment, in 3D cultures which preserved the inflammatory microenvironment and/or in 2D cultures which mimicked it.
results3D human hippocampal cultures largely replicated the cellular composition and inflammatory environment of the epileptic hippocampus. The microenvironment of sclerotic human epileptic hippocampal tissue is strongly anti-neurogenic, with sustained release of the proinflammatory proteins HMGB1 and IL-1β. IL-1β and HMGB1 significantly reduce human hippocampal neurogenesis and blockade of their IL-1R and TLR 2/4 receptors by IL1Ra and Box-A respectively, significantly restores neurogenesis in 2D and 3D culture.
conclusionOur results demonstrate a HMGB1 and IL-1β-mediated environmental anti-neurogenic effect in human TLE, identifying both the IL-1R and TLR 2/4 receptors as potential drug targets for restoring human hippocampal neurogenesis in temporal lobe epilepsy.
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