ArticleNeurobiology of disease2015
Toll-like receptor 4 enhancement of non-NMDA synaptic currents increases dentate excitability after brain injury.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 59 citations in OpenAlex.
- Neuronal toll-like receptor-4 regulation of matrix metalloproteinase-9 activity mediates dentate circuit dysfunction after traumatic brain injury.Journal of neuroinflammation · 2026Article
- Neuronal Toll-like Receptor-4 regulation of Matrix Metalloproteinase-9 Activity Mediates Dentate Circuit Dysfunction after Traumatic Brain Injury.bioRxiv : the preprint server for biology · 2026Article
- Administration of monophosphoryl lipid A shortly after traumatic brain injury blocks the following spatial and avoidance memory loss and neuroinflammation.Scientific reports · 2024Article
- Gentiopicroside Attenuates Lithium/Pilocarpine-Induced Epilepsy Seizures by Down-Regulating NR2B/CaMKII/CREB and TLR4/NF-κB Signaling Pathways in the Hippocampus of Mice.Pharmaceuticals (Basel, Switzerland) · 2024Article
- An overview of preclinical models of traumatic brain injury (TBI): relevance to pathophysiological mechanisms.Frontiers in cellular neuroscience · 2024Review
- Early deficits in dentate circuit and behavioral pattern separation after concussive brain injury.Experimental neurology · 2023Article
- Anti-inflammatory drugs prevent memory and hippocampal plasticity deficits following initial binge-like alcohol exposure in adolescent male rats.Psychopharmacology · 2022Article
- Article
- Long-Term Effects of Moderate Concussive Brain Injury During Adolescence on Synaptic and Tonic GABA Currents in Dentate Granule Cells and Semilunar Granule Cells.Frontiers in neuroscience · 2022Article
- Hyperacute Excitotoxic Mechanisms and Synaptic Dysfunction Involved in Traumatic Brain Injury.Frontiers in molecular neuroscience · 2022Review
- Blocking receptor for advanced glycation end products (RAGE) or toll-like receptor 4 (TLR4) prevents posttraumatic epileptogenesis in mice.Epilepsia · 2021Article
- Sensory Neuron TLR4 mediates the development of nerve-injury induced mechanical hypersensitivity in female mice.Brain, behavior, and immunity · 2021Article
- Magnesium Citrate Increases Pain Threshold and Reduces TLR4 Concentration in the Brain.Biological trace element research · 2021Article
- Review
- Presynaptic L-Type CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- CurrentCurrent opinion in biomedical engineering · 2020Article
- Toll-like Receptor 4 Signaling in Neurons Enhances Calcium-Permeable α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Currents and Drives Post-Traumatic Epileptogenesis.Annals of neurology · 2020Article
- Kaempferol Treatment after Traumatic Brain Injury during Early Development Mitigates Brain Parenchymal Microstructure and Neural Functional Connectivity Deterioration at Adolescence.Journal of neurotrauma · 2020Article
- Converging early responses to brain injury pave the road to epileptogenesis.Journal of neuroscience research · 2019Review
- Animal Models of Traumatic Brain Injury and Assessment of Injury Severity.Molecular neurobiology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Concussive brain injury results in neuronal degeneration, microglial activation and enhanced excitability in the hippocampal dentate gyrus, increasing the risk for epilepsy and memory dysfunction. Endogenous molecules released during injury can activate innate immune responses including toll-like receptor 4 (TLR4). Recent studies indicate that immune mediators can modulate neuronal excitability. Since non-specific agents that reduce TLR4 signaling can limit post-traumatic neuropathology, we examined whether TLR4 signaling contributes to early changes in dentate excitability after brain injury. Concussive brain injury caused a transient increase in hippocampal TLR4 expression within 4h, which peaked at 24h. Post-injury increase in TLR4 expression in the dentate gyrus was primarily neuronal and persisted for one week. Acute, in vitro treatment with TLR4 ligands caused bidirectional modulation of dentate excitability in control and brain-injured rats, with a reversal in the direction of modulation after brain injury. TLR4 antagonists decreased, and agonist increased, afferent-evoked dentate excitability one week after brain injury. NMDA receptor antagonist did not occlude the ability of LPS-RS, a TLR4 antagonist, to decrease post-traumatic dentate excitability. LPS-RS failed to modulate granule cell NMDA EPSCs but decreased perforant path-evoked non-NMDA EPSC peak amplitude and charge transfer in both granule cells and mossy cells. Our findings indicate an active role for TLR4 signaling in early post-traumatic dentate hyperexcitability. The novel TLR4 modulation of non-NMDA glutamatergic currents, identified herein, could represent a general mechanism by which immune activation influences neuronal excitability in neurological disorders that recruit sterile inflammatory responses.
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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.