Adipose-derived stem cell exosomes suppress NLRP3-mediated neuronal pyroptosis to attenuate seizures in a kainic acid-induced temporal lobe epilepsy model.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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. 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. 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

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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