Neuroinflammatory reactive astrocyte formation correlates with adverse outcomes in perinatal white matter injury.
Glia
; 72(9): 1663-1673, 2024 09.
Article
in En
| MEDLINE
| ID: mdl-38924630
ABSTRACT
Perinatal white matter injury (WMI) is the leading cause of long-term neurological morbidity in infants born preterm. Neuroinflammation during a critical window of early brain development plays a key role in WMI disease pathogenesis. The mechanisms linking inflammation with the long-term myelination failure that characterizes WMI, however, remain unknown. Here, we investigate the role of astrocyte reactivity in WMI. In an experimental mouse model of WMI, we demonstrate that WMI disease outcomes are improved in mutant mice lacking secretion of inflammatory molecules TNF-α, IL-1α, and C1q known, in addition to other roles, to induce the formation of a neuroinflammatory reactive astrocyte substate. We show that astrocytes express molecular signatures of the neuroinflammatory reactive astrocyte substate in both our WMI mouse model and human tissue affected by WMI, and that this gene expression pattern is dampened in injured mutant mice. Our data provide evidence that a neuroinflammatory reactive astrocyte substate correlates with adverse WMI disease outcomes, thus highlighting the need for further investigation of these cells as potential causal players in WMI pathology.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Astrocytes
/
White Matter
/
Animals, Newborn
Limits:
Animals
/
Female
/
Humans
/
Newborn
Language:
En
Journal:
Glia
Journal subject:
NEUROLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Suiza
Country of publication:
Estados Unidos