Neuroprotective Effects of Early TLR4 Blockade with Compound C34 in Temporal Lobe Epilepsy: Alleviation of Neuroinflammation and Apoptosis
| Author | Roya Varmazyar | en |
| Author | Nima Naderi | en |
| Author | Hanieh Javid | en |
| Author | Rasoul Ghasemi | en |
| Author | Hamid Gholami Pourbadie | en |
| Issued Date | 2025-12-31 | en |
| Abstract | 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-α, which contribute to neuronal injury and apoptosis. The TLR4 signaling pathway promotes neuroinflammation through nuclear factor kappa-B (NF-κB) 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-κB1 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-κB1, TNF-α, and caspase-3 were analyzed using western blotting. Neuronal death in the hippocampus was assessed using hematoxylin and eosin (H&E) staining. Results: The results demonstrated that early inhibition of TLR4 by C34, administered immediately after seizure induction, significantly reduced NF-κB1, TNF-α, 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. | en |
| DOI | https://doi.org/10.5812/ijpr-159165 | en |
| Keyword | Apoptosis | en |
| Keyword | C34 | en |
| Keyword | NF-κB1 | en |
| Keyword | Pilocarpine | en |
| Keyword | Status Epilepticus | en |
| Keyword | TLR4 | en |
| Keyword | TNF-a | en |
| Publisher | Brieflands | en |
| Title | Neuroprotective Effects of Early TLR4 Blockade with Compound C34 in Temporal Lobe Epilepsy: Alleviation of Neuroinflammation and Apoptosis | en |
| Type | Research Article | en |