ArticleEpilepsia2021
Blocking receptor for advanced glycation end products (RAGE) or toll-like receptor 4 (TLR4) prevents posttraumatic epileptogenesis in mice.
Article in Epilepsia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- Deconstructing the RAGE signaling maze: the molecular key to opening a new dimension of ovarian anti-aging.Experimental & molecular medicine · 2026Review
- Innate immune signalling, neuroinflammation and network plasticity in temporal lobe epilepsy.Frontiers in pharmacology · 2026Review
- Neuroprotective Effects of the Nonsteroidal Anti-inflammatory Drug Celecoxib Against Caspase-1-dependent Pyroptosis Partially by Suppressing the HMGB1/TLR4 Pathway.Cellular and molecular neurobiology · 2025Article
- "Targeting Neuroimmune Pathways in Epilepsy: Advances in Mechanisms and Emerging Therapeutics".Neurochemical research · 2025Review
- Post-traumatic epilepsy: bridging pathogenesis, diagnosis, and pharmacotherapeutic strategies.Frontiers in pharmacology · 2025Review
- Ulinastatin modulates NLRP3 inflammasome pathway in PTZ-induced epileptic mice: A potential mechanistic insight.Heliyon · 2024Article
- mTOR and neuroinflammation in epilepsy: implications for disease progression and treatment.Nature reviews. Neuroscience · 2024Review
- Targeting CCL5 signaling attenuates neuroinflammation after seizure.CNS neuroscience & therapeutics · 2023Article
- Inhibition of TRPC3 channels by a novel pyrazole compound confers antiseizure effects.Epilepsia · 2022Article
- Silencing TLR4 using an ultrasound-targeted microbubble destruction-based shRNA system reduces ischemia-induced seizures in hyperglycemic rats.Open life sciences · 2022Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
objectiveEffective treatment for the prevention of posttraumatic epilepsy is still not available. Here, we sought to determine whether blocking receptor for advanced glycation end products (RAGE) or toll-like receptor 4 (TLR4) signaling pathways would prevent posttraumatic epileptogenesis.
methodsIn a mouse undercut model of posttraumatic epilepsy, daily injections of saline, RAGE monoclonal antibody (mAb), or TAK242, a TLR4 inhibitor, were made for 1 week. Their effects on seizure susceptibility and spontaneous epileptic seizures were evaluated with a pentylenetetrazol (PTZ) test in 2 weeks and with continuous video and wireless electroencephalography (EEG) monitoring between 2 and 6 weeks after injury, respectively. Seizure susceptibility after undercut in RAGE knockout mice was also evaluated with the PTZ test. The lesioned cortex was analyzed with immunohistology.
resultsUndercut animals treated with RAGE mAb or TAK242 showed significantly higher seizure threshold than saline-treated undercut mice. Consistently, undercut injury in RAGE knockout mice did not cause a reduction in seizure threshold in the PTZ test. EEG and video recordings revealed a significant decrease in the cumulative spontaneous seizure events in the RAGE mAb- or TAK242-treated group (p < 0.001, when the RAGE mAb or TAK242 group is compared with the saline group). The lesioned cortical tissues of RAGE mAb- or TAK242-treated undercut group showed higher neuronal densities of Nissl staining and higher densities of glutamic acid decarboxylase 67-immunoreactive interneurons than the saline-treated undercut group. Immunostaining to GFAP and Iba-1 revealed lower densities of astrocytes and microglia in the cortex of the treatment groups, suggesting reduced glia activation. SIGNIFICANCE: RAGE and TLR4 signaling are critically involved in posttraumatic epileptogenesis. Blocking these pathways early after traumatic brain injury is a promising strategy for preventing posttraumatic epilepsy.
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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.