Back to Search
Start Over
CSF1R blockade slows progression of cerebral hemorrhage by reducing microglial proliferation and increasing infiltration of CD8 + CD122+ T cells into the brain.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2024 May 30; Vol. 133, pp. 112071. Date of Electronic Publication: 2024 Apr 17. - Publication Year :
- 2024
-
Abstract
- Microglia play a pivotal role in the neuroinflammatory response after brain injury, and their proliferation is dependent on colony-stimulating factors. In the present study, we investigated the effect of inhibiting microglia proliferation on neurological damage post intracerebral hemorrhage (ICH) in a mouse model, an aspect that has never been studied before. Using a colony-stimulating factor-1 receptor antagonist (GW2580), we observed that inhibition of microglia proliferation significantly ameliorated neurobehavioral deficits, attenuated cerebral edema, and reduced hematoma volume after ICH. This intervention was associated with a decrease in pro-inflammatory factors in microglia and an increased infiltration of peripheral regulatory CD8 + CD122+ T cells into the injured brain tissue. The CXCR3/CXCL10 axis is the mechanism of brain homing of regulatory CD8 + CD122+ T cells, and the high expression of IL-10 is the hallmark of their synergistic anti-inflammatory effect with microglia. And activated astrocytes around the insult site are a prominent source of CXCL10. Thus, inhibition of microglial proliferation offers a new perspective for clinical translation. The cross-talk between multiple cells involved in the regulation of the inflammatory response highlights the comprehensive nature of neuroimmunomodulation.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Male
Mice
Anisoles
Cell Proliferation drug effects
Chemokine CXCL10 metabolism
Disease Models, Animal
Interleukin-10 metabolism
Interleukin-2 Receptor beta Subunit metabolism
Mice, Inbred C57BL
Pyrimidines
Receptors, CXCR3 metabolism
Receptors, CXCR3 antagonists & inhibitors
Brain pathology
Brain drug effects
Brain metabolism
Brain immunology
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes drug effects
Cerebral Hemorrhage drug therapy
Cerebral Hemorrhage immunology
Microglia drug effects
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor antagonists & inhibitors
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 133
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 38636374
- Full Text :
- https://doi.org/10.1016/j.intimp.2024.112071