Neuroinflammatory reactive astrocyte formation correlates with adverse outcomes in perinatal white matter injury.

Renz, Patricia; Steinfort, Marel; Haesler, Valérie; Tscherrig, Vera; Huang, Eric J; Chavali, Manideep; Liddelow, Shane; Rowitch, David H; Surbek, Daniel; Schoeberlein, Andreina; Brosius Lutz, Amanda (2024). Neuroinflammatory reactive astrocyte formation correlates with adverse outcomes in perinatal white matter injury. Glia, 72(9), pp. 1663-1673. Wiley 10.1002/glia.24575

Preview

Text Glia_-_2024_-_Renz_-_Neuroinflammatory_reactive_astrocyte_formation_correlates_with_adverse_outcomes_in_perinatal_white.pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND). Download (6MB) | Preview

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.

Interest & Impact

Downloads

14 since deposited on 27 Jun 2024
14 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item