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Subventricular zone-derived extracellular vesicles promote functional recovery in rat model of spinal cord injury by inhibition of NLRP3 inflammasome complex formation

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Abstract

Spinal cord injury (SCI) is the destruction of spinal cord motor and sensory resulted from an attack on the spinal cord, which can cause significant physiological damage. The inflammasome is a multiprotein oligomer resulting in inflammation; the NLRP3 inflammasome composed of NLRP3, apoptosis-associated speck-like protein (ASC), procaspase-1, and cleavage of procaspase-1 into caspase-1 initiates the inflammatory response. Subventricular Zone (SVZ) is the origin of neural stem/progenitor cells (NS/PCs) in the adult brain. Extracellular vesicles (EVs) are tiny lipid membrane bilayer vesicles secreted by different types of cells playing an important role in cell-cell communications. The aim of this study was to investigate the effect of intrathecal transplantation of EVs on the NLRP3 inflammasome formation in SCI rats. Male wistar rats were divided into three groups as following: laminectotomy group, SCI group, and EVs group. EVs was isolated from SVZ, and characterized by western blot and DLS, and then injected into the SCI rats. Real-time PCR and western blot were carried out for gene expression and protein level of NLRP3, ASC, and Caspase-1. H&E and cresyl violet staining were performed for histological analyses, as well as BBB test for motor function. The results indicated high level in mRNA and protein level in SCI group in comparison with laminectomy (p < 0.001), and injection of EVs showed a significant reduction in the mRNA and protein levels in EVs group compared to SCI (p < 0.001). H&E and cresyl violet staining showed recovery in neural cells of spinal cord tissue in EVs group in comparison with SCI group. BBB test showed the promotion of motor function in EVs group compared to SCI in 14 days (p < 0.05). We concluded that the injection of EVs could recover the motor function in rats with SCI and rescue the neural cells of spinal cord tissue by suppressing the formation of the NLRP3 inflammasome complex.

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Acknowledgements

This study was funded by Tehran University of Medical Sciences (No. 97-01-103-37391).

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Authors and Affiliations

  1. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Ibrahim Mohammed, Sahar Ijaz, Morteza Gholaminejhad, Marzieh Mahdavipour, Mohammad Akbari & Gholamreza Hassanzadeh

  2. CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China

    Tahmineh Mokhtari

  3. Department of Psychology, University of Chinese Academy of Sciences, Beijing, China

    Tahmineh Mokhtari

  4. Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran

    Behnamedin Jameie

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  1. Ibrahim Mohammed
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Mohammed, I., Ijaz, S., Mokhtari, T. et al. Subventricular zone-derived extracellular vesicles promote functional recovery in rat model of spinal cord injury by inhibition of NLRP3 inflammasome complex formation. Metab Brain Dis 35, 809–818 (2020). https://doi.org/10.1007/s11011-020-00563-w

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