Exosome-based therapy for epilepsy: a systematic review and meta-analysis of preclinical studies

This study aims to quantitatively assess the efficacy of exosome therapy for epilepsy through a systematic review and meta-analysis of preclinical animal experiments. We seek to clarify its overall effects on seizure reduction, cognitive function preservation, and neuroinflammation suppression.

A systematic search was conducted across four English-language and four Chinese databases to include epilepsy animal studies. Continuous outcomes were synthesized using standardized mean differences (SMD) and 95% confidence intervals (CI), with fixed or random effects models selected based on heterogeneity.

A total of eight preclinical studies were included. The overall meta-analysis revealed that exosome treatment significantly reduced the duration of seizures (SMD = -2.30, 95% CI -4.24 to -0.36), decreased the frequency of spontaneous recurrent seizures (SMD = -1.38, 95% CI -2.17 to -0.58), and prolonged the seizure latency (SMD = 1.49, 95% CI 0.08-2.90). In terms of cognitive function, exosomes significantly shortened the escape latency in the Morris water maze (SMD = -1.38, 95% CI -2.17 to -0.58), increased the percentage of time spent in the target quadrant (SMD = 3.69, 95% CI 0.30-7.08), and enhanced the number of platform crossings (SMD = 1.41, 95% CI 0.60-2.21), with no significant changes in swimming speed. Neuropathological analysis indicated that exosome treatment significantly increased the number of hippocampal neurons (SMD = 4.48, 95% CI 1.46-7.49) and markedly reduced levels of glial fibrillary acidic protein (GFAP) (SMD = -3.61, 95% CI -7.08 to -0.14), ionized calcium-binding adaptor molecule 1 (IBA-1) (SMD = -10.27, 95% CI -20.29 to -0.25), tumor necrosis factor-alpha (TNF-α) (SMD = -2.95, 95% CI -4.21 to -1.69), and interleukin-1 beta (IL-1β) (SMD = -7.39, 95% CI -14.64 to -0.13). Although some outcomes exhibited heterogeneity and publication bias, the corrected primary effects remained statistically significant. The source of exosomes, administration route, and dosage may be critical variables influencing their efficacy.

Exosome therapy improves seizure phenotypes and protects cognitive function in epilepsy models by suppressing neuroinflammation to promote neuronal survival, providing evidence for further mechanistic and clinical translation studies.