ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1691814
This article is part of the Research TopicDecoding Chronic Inflammation: The Role of Immune Cell CommunicationView all 5 articles
Adipose-derived stem cell exosomes suppress NLRP3-mediated neuronal pyroptosis to attenuate seizures in a kainic acid-induced temporal lobe epilepsy model
Provisionally accepted
- 1Yiwu Central Hospital, Yiwu, China
- 2First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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Background: Pyroptosis-mediated neuroinflammation represents a critical pathological mechanism in drug-resistant temporal lobe epilepsy (TLE),while Adipose-derived stem cell exosomes (ADSC-Exos) may target this process through NLRP3 inflammasome inhibition. Our study investigated the therapeutic effects of ADSC-Exos by mitigating NLRP3-driven pyroptosis in TLE. Methods: We isolated ADSC-Exos, the characteristics of which were confirmed. The Kainic acid-induced mouse TLE model were used to assess the in vivo effect of ADSC-Exos. To evaluate ADSC-Exos penetration, brain tissues were collected for fluorescence quantification. TUNEL and Nissl staining were used to evaluate hippocampal neuronal damage. Pyroptosis markers were detected by Western blot, qRT-PCR, and immunofluorescence. Bioinformatics analysis was performed to explore potential miRNAs in ADSC-Exos that might contribute to their therapeutic effects. Results: Intravenously injected ADSC-Exos efficiently crossed the blood-brain barrier, peaking in brain accumulation at 4 hours post-administration. Treatment with ADSC-Exos resulted in a 48.9% reduction in seizure duration (p<0.0001) and a 42% reduction in spontaneous recurrent seizure frequency (p<0.0001) in temporal lobe epilepsy. Furthermore, ADSC-Exos exhibited significant neuroprotection while suppressing key pyroptosis-related proteins, including NLRP3, Caspase-1, GSDMD, and IL-1β. Bioinformatics analysis further identified 16 candidate miRNAs in ADSC-Exos potentially mediating these therapeutic effects. Conclusions: ADSC-Exos exert neuroprotective effects in temporal lobe epilepsy in association with regulation of the NLRP3-associated pyroptosis pathway, thereby suppressing neuroinflammation and neuronal death, highlighting their potential therapeutic value.
Keywords: adipose-derived stem cells, Exosomes, Temporal Lobe Epilepsy, NLRP3, pyroptosis
Received: 24 Aug 2025; Accepted: 14 Oct 2025.
Copyright: © 2025 Ding, Chen, E, Zhou, Zhao, Chen, Dong, Dai and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yucang He, heyucang0@163.com
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