hUC-MSC extracellular vesicles protect against hypoxic-ischemic brain injury by promoting NLRP3 ubiquitination
Hypoxic-ischemic brain injury (HIBD) is a major cause of neonatal mortality and long-term neurological deficits, with limited treatment options. Extracellular vesicles (EVs) from human umbilical cord mesenchymal stem cells (hUC-MSC-EVs) have shown promise in neuroprotection, but the mechanisms remai...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2024-12-01
|
| Series: | Biomolecules & Biomedicine |
| Subjects: | |
| Online Access: | https://www.bjbms.org/ojs/index.php/bjbms/article/view/10706 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841557145160515584 |
|---|---|
| author | Shanshan Xiao Ying Lv Xuejing Hou Shuqiang Qu |
| author_facet | Shanshan Xiao Ying Lv Xuejing Hou Shuqiang Qu |
| author_sort | Shanshan Xiao |
| collection | DOAJ |
| description | Hypoxic-ischemic brain injury (HIBD) is a major cause of neonatal mortality and long-term neurological deficits, with limited treatment options. Extracellular vesicles (EVs) from human umbilical cord mesenchymal stem cells (hUC-MSC-EVs) have shown promise in neuroprotection, but the mechanisms remain unclear. This study explores how hUC-MSC-EVs protect neonatal rats from HIBD. hUC-MSC-EVs were isolated, characterized, and administered to neonatal rats subjected to HIBD. Behavioral reflexes and brain infarction were assessed, along with cellular and molecular analyses of hippocampal tissue. An in vitro oxygen–glucose deprivation/reoxygenation (OGD/R) model was used to simulate ischemic conditions in rat primary microglia. Results demonstrated that hUC-MSC-EVs significantly improved neurological outcomes, reduced brain infarction, and decreased microglial activation and pyroptosis. These effects were linked to the inhibition of NLRP3 inflammasome activation and enhanced ubiquitination via the protein kinase A (PKA) pathway. Blocking PKA partially reversed these protective effects. Here we highlight that hUC-MSC-EVs provide neuroprotection by regulating the NLRP3 inflammasome, offering a potential therapeutic strategy for HIBD. These findings expand the understanding of EV-mediated neuroprotection and suggest broader applications for ischemia-related conditions, with potential for clinical translation.
|
| format | Article |
| id | doaj-art-32a5459a65664d42b00966164b18f9d6 |
| institution | Kabale University |
| issn | 2831-0896 2831-090X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
| record_format | Article |
| series | Biomolecules & Biomedicine |
| spelling | doaj-art-32a5459a65664d42b00966164b18f9d62025-01-06T16:39:06ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2024-12-0110.17305/bb.2024.10706hUC-MSC extracellular vesicles protect against hypoxic-ischemic brain injury by promoting NLRP3 ubiquitinationShanshan Xiao0Ying Lv1Xuejing Hou 2Shuqiang Qu3Department of Pediatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Pediatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Pediatrics, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Pediatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaHypoxic-ischemic brain injury (HIBD) is a major cause of neonatal mortality and long-term neurological deficits, with limited treatment options. Extracellular vesicles (EVs) from human umbilical cord mesenchymal stem cells (hUC-MSC-EVs) have shown promise in neuroprotection, but the mechanisms remain unclear. This study explores how hUC-MSC-EVs protect neonatal rats from HIBD. hUC-MSC-EVs were isolated, characterized, and administered to neonatal rats subjected to HIBD. Behavioral reflexes and brain infarction were assessed, along with cellular and molecular analyses of hippocampal tissue. An in vitro oxygen–glucose deprivation/reoxygenation (OGD/R) model was used to simulate ischemic conditions in rat primary microglia. Results demonstrated that hUC-MSC-EVs significantly improved neurological outcomes, reduced brain infarction, and decreased microglial activation and pyroptosis. These effects were linked to the inhibition of NLRP3 inflammasome activation and enhanced ubiquitination via the protein kinase A (PKA) pathway. Blocking PKA partially reversed these protective effects. Here we highlight that hUC-MSC-EVs provide neuroprotection by regulating the NLRP3 inflammasome, offering a potential therapeutic strategy for HIBD. These findings expand the understanding of EV-mediated neuroprotection and suggest broader applications for ischemia-related conditions, with potential for clinical translation. https://www.bjbms.org/ojs/index.php/bjbms/article/view/10706Mesenchymal stem cellsMSCsextracellular vesiclesEVshypoxia-ischemiaHI |
| spellingShingle | Shanshan Xiao Ying Lv Xuejing Hou Shuqiang Qu hUC-MSC extracellular vesicles protect against hypoxic-ischemic brain injury by promoting NLRP3 ubiquitination Biomolecules & Biomedicine Mesenchymal stem cells MSCs extracellular vesicles EVs hypoxia-ischemia HI |
| title | hUC-MSC extracellular vesicles protect against hypoxic-ischemic brain injury by promoting NLRP3 ubiquitination |
| title_full | hUC-MSC extracellular vesicles protect against hypoxic-ischemic brain injury by promoting NLRP3 ubiquitination |
| title_fullStr | hUC-MSC extracellular vesicles protect against hypoxic-ischemic brain injury by promoting NLRP3 ubiquitination |
| title_full_unstemmed | hUC-MSC extracellular vesicles protect against hypoxic-ischemic brain injury by promoting NLRP3 ubiquitination |
| title_short | hUC-MSC extracellular vesicles protect against hypoxic-ischemic brain injury by promoting NLRP3 ubiquitination |
| title_sort | huc msc extracellular vesicles protect against hypoxic ischemic brain injury by promoting nlrp3 ubiquitination |
| topic | Mesenchymal stem cells MSCs extracellular vesicles EVs hypoxia-ischemia HI |
| url | https://www.bjbms.org/ojs/index.php/bjbms/article/view/10706 |
| work_keys_str_mv | AT shanshanxiao hucmscextracellularvesiclesprotectagainsthypoxicischemicbraininjurybypromotingnlrp3ubiquitination AT yinglv hucmscextracellularvesiclesprotectagainsthypoxicischemicbraininjurybypromotingnlrp3ubiquitination AT xuejinghou hucmscextracellularvesiclesprotectagainsthypoxicischemicbraininjurybypromotingnlrp3ubiquitination AT shuqiangqu hucmscextracellularvesiclesprotectagainsthypoxicischemicbraininjurybypromotingnlrp3ubiquitination |