{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:18:52Z","timestamp":1787728732728,"version":"build-2784847793"},"reference-count":31,"publisher":"Brieflands","issue":"1","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["brieflands.com"],"crossmark-restriction":false},"short-container-title":["Iran J Pharm Res"],"abstract":"<jats:p>Background: Temporal lobe epilepsy (TLE) is a chronic neurological disorder characterized by hippocampal necrosis and apoptosis. Neuroinflammation plays a critical role in the pathophysiology of TLE, with toll-like receptor 4 (TLR4) serving as a key mediator. Activation of TLR4 leads to the release of pro-inflammatory cytokines, such as IL-6 and TNF-\u03b1, which contribute to neuronal injury and apoptosis. The TLR4 signaling pathway promotes neuroinflammation through nuclear factor kappa-B (NF-\u03baB) activation, further exacerbating neuronal damage over time. Therefore, timely inhibition of TLR4 may help mitigate neuroinflammation and alleviate epilepsy symptoms. Objectives: This study aimed to determine whether early inhibition of TLR4 can regulate seizures and apoptosis by targeting the NF-\u03baB1 signaling pathway. Methods: The TLR4 inhibitor C34 was administered intraventricularly to two experimental groups. The first group received the injection immediately after pilocarpine-induced seizures, while the second group was treated 24 hours post-pilocarpine injection. The expression levels of NF-\u03baB1, TNF-\u03b1, and caspase-3 were analyzed using western blotting. Neuronal death in the hippocampus was assessed using hematoxylin and eosin (H&amp;E) staining. Results: The results demonstrated that early inhibition of TLR4 by C34, administered immediately after seizure induction, significantly reduced NF-\u03baB1, TNF-\u03b1, and caspase-3 expression levels compared to the group that received C34, 24 hours later. Additionally, early treatment with C34 significantly prevented pilocarpine-induced neuronal death in the hippocampus compared to the late treatment group. Conclusions: These findings highlight the importance of early intervention in reducing neuronal death and suppressing neuroinflammation in an epilepsy model. Inhibiting TLR4 immediately after seizure induction may serve as a potential therapeutic strategy to minimize inflammation-mediated neuronal damage in TLE. Further research is needed to explore the long-term effects of TLR4 inhibition in epilepsy treatment.<\/jats:p>","DOI":"10.5812\/ijpr-159165","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T04:11:21Z","timestamp":1741579881000},"update-policy":"https:\/\/doi.org\/10.5812\/crossmark_update_policy","source":"Crossref","is-referenced-by-count":2,"title":["Neuroprotective Effects of Early TLR4 Blockade with Compound C34 in Temporal Lobe Epilepsy: Alleviation of Neuroinflammation and 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