2. Academic Validation
  3. Exosomes derived from neural stem cells contribute to cerebral ischemia/reperfusion injury via inhibiting autophagy in rats

Exosomes derived from neural stem cells contribute to cerebral ischemia/reperfusion injury via inhibiting autophagy in rats

  • J Neuroimmunol. 2026 Apr:413:578875. doi: 10.1016/j.jneuroim.2026.578875.
Li Xiong 1,  Siying Huo 2,  Yuan Yang 2,  Qi Zhang 2,  Junjie Li 2,  Wenya Bai 2,  Jia Liu 3,  Jianlin Shao 4
Affiliations

Affiliations

  • 1 Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, PR China; Department of Anesthesiology, The Third People's Hospital of Yibin, Sichuan Province, PR China.
  • 2 Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, PR China.
  • 3 Department of Laboratory Zoology, Kunming Medical University, PR China. Electronic address: [email protected].
  • 4 Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, PR China. Electronic address: [email protected].
PMID: 41619451 DOI: 10.1016/j.jneuroim.2026.578875
Abstract

Background: Cerebral ischemia-reperfusion injury (CIRI) represents a critical pathological mechanism underlying stroke. Exosomes (EXOs) are biological vesicles released by cells, containing active components and functional properties of their cell of origin. This study investigates the impact of human neural stem cell-derived exosomes (hNSC-EXOs) on the CIRI rat model, focusing on neuronal Autophagy, and provides a novel theoretical foundation for future clinical interventions in CIRI management.

Methods: PKH26-labeled hNSC-EXOs were traced in vivo and in vitro. After establishing CIRI model, hNSC-EXOs were administered for treatment. Brain injury and variations in inflammatory factors were compared at 24 h after operation. The impact of hNSC-EXOs on neuronal Autophagy was examined by detecting the expression of Beclin-1, Atg-5, and LC3B, and observing the changes in the number of autophagosomes using TEM of the right cerebral cortex of rats.

Results: The average particle size and concentration of hNSC-EXO were 64.47 nm and 8.96 × 1010/ml, respectively. PKH26-labeled hNSC-EXOs was taken up by BV2 and HT22 cells, and was mainly located in the brain injury area in vivo, with their total flux showing a time-dependent characteristic. hNSC-EXO treatment reduced the neurological score, cerebral infarct volume, and cerebral edema in the CIRI model. Brain tissue staining showed that hNSC-EXO attenuated Nissl body damage and neuronal Apoptosis in the CIRI model. Regarding inflammatory factors, hNSC-EXO increased serum levels of IL-4 and IL-10, and decreased levels of TNF-α, iNOS, and IL-6 in the CIRI model. Notably, hNSC-EXO reduced the expression of Beclin-1, Atg-5, and LC3 and the number of autophagosomes in the brain tissue of the CIRI model.

Conclusion: hNSC-EXOs exert an antagonistic effect with CIRI, effectively inhibiting excessive neuronal Autophagy, reducing the inflammatory response and neuronal Apoptosis.

Keywords

Autophagy; Cerebral ischemia-reperfusion injury; Exosomes; Inflammation; Neural stem cell.

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