Exosomes derived from mesenchymal stem cells alleviate white matter damage in neonatal rats by targeting the NLRP3 inflammasome.
10.7499/j.issn.1008-8830.2504160
- Author:
Chao WANG
1
;
Yan-Ping ZHU
;
BAYIERCAICIKE
;
Yu-Qing FENG
;
Yan-Mei WANG
Author Information
1. Department of Neonatology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
- Publication Type:Journal Article
- Keywords:
Exosome;
Mesenchymal stem cell;
Neonatal rat;
Nucleotide-binding oligomerization domain-like receptor protein 3;
White matter damage
- MeSH:
Animals;
NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors*;
Rats, Sprague-Dawley;
White Matter/pathology*;
Inflammasomes/physiology*;
Rats;
Animals, Newborn;
Mesenchymal Stem Cells;
Interleukin-1beta/analysis*;
Male;
Caspase 1/analysis*;
Hypoxia-Ischemia, Brain/therapy*;
Myelin Basic Protein/analysis*
- From:
Chinese Journal of Contemporary Pediatrics
2025;27(9):1119-1127
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate whether mesenchymal stem cell-derived exosomes (MSC-Exo) alleviate white matter damage (WMD) in neonatal rats by targeting the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3).
METHODS:Three-day-old Sprague-Dawley rats were randomly assigned to four groups: Sham, hypoxia-ischemia (HI), MSC-Exo, and MCC950 (NLRP3 inhibitor) (n=24 per group). The WMD model was established by unilateral common carotid artery ligation combined with hypoxia. Exosomes (1×108 particles/μL) were transplanted into the lateral ventricle using stereotaxic guidance. Fourteen days after modeling, hematoxylin-eosin staining was used to observe pathological changes in brain tissue, and transmission electron microscopy was used to assess myelinated axons. Western blotting was performed to detect the expression of myelin basic protein (MBP), NLRP3, caspase-1, and interleukin-1β (IL-1β). Immunohistochemistry was used to measure NLRP3, caspase-1, and IL-1β expression. Twenty-eight days post-modeling, behavioral changes were evaluated using the Morris water maze.
RESULTS:In the HI group, marked inflammatory cell infiltration, extensive vacuolation, and decreased numbers of myelinated axons were observed compared to the Sham group. The MSC-Exo group showed reduced inflammatory infiltration, fewer vacuoles, and increased myelinated axons compared to the HI group, while the MCC950 group showed nearly normal cell morphology. Compared to the Sham group, the HI group exhibited decreased MBP expression, fewer platform crossings, shorter time in the target quadrant, increased expression of NLRP3, caspase-1, and IL-1β, and longer escape latency (all P<0.05). Compared to the HI group, the MSC-Exo and MCC950 groups showed increased MBP expression, more platform crossings, longer target quadrant stay, and reduced NLRP3, caspase-1, and IL-1β expression, as well as shorter escape latency (all P<0.05).
CONCLUSIONS:MSC-Exo may attenuate white matter damage in neonatal rats by targeting the NLRP3 inflammasome and promoting oligodendrocyte maturation.
