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

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-associ...

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Veröffentlicht in:Metabolic brain disease 2020-06, Vol.35 (5), p.809-818
Hauptverfasser: Mohammed, Ibrahim, Ijaz, Sahar, Mokhtari, Tahmineh, Gholaminejhad, Morteza, Mahdavipour, Marzieh, Jameie, Behnamedin, Akbari, Mohammad, Hassanzadeh, Gholamreza
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container_issue 5
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container_title Metabolic brain disease
container_volume 35
creator Mohammed, Ibrahim
Ijaz, Sahar
Mokhtari, Tahmineh
Gholaminejhad, Morteza
Mahdavipour, Marzieh
Jameie, Behnamedin
Akbari, Mohammad
Hassanzadeh, Gholamreza
description 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  
doi_str_mv 10.1007/s11011-020-00563-w
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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&amp;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  &lt; 0.001), and injection of EVs showed a significant reduction in the mRNA and protein levels in EVs group compared to SCI ( p  &lt; 0.001). H&amp;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  &lt; 0.05). 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H&amp;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  &lt; 0.001), and injection of EVs showed a significant reduction in the mRNA and protein levels in EVs group compared to SCI ( p  &lt; 0.001). H&amp;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  &lt; 0.05). 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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&amp;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  &lt; 0.001), and injection of EVs showed a significant reduction in the mRNA and protein levels in EVs group compared to SCI ( p  &lt; 0.001). H&amp;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  &lt; 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.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>32185593</pmid><doi>10.1007/s11011-020-00563-w</doi><tpages>10</tpages></addata></record>
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subjects Animal models
Apoptosis
Biochemistry
Biomedical and Life Sciences
Biomedicine
Blood-brain barrier
Caspase-1
Cells (biology)
Complex formation
Extracellular vesicles
Gene expression
Inflammasomes
Inflammation
Inflammatory response
Injection
Lipids
Membrane vesicles
Metabolic Diseases
Neural stem cells
Neurology
Neurosciences
Oncology
Original Article
Progenitor cells
Proteins
Recovery
Recovery of function
Rodents
Spinal cord injuries
Staining
Subventricular zone
Transplantation
Vesicles
title 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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