Journal Article

DZNE-2026-01001

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Loss of C3 and CD14 reduces region-specific neuroinflammation in a murine polytrauma model.

Olde Heuvel, F. ; Pagliarini, M. (First author)DZNE* ; Sun, F. ; Lupu, L. ; Zhao, Z. ; Cui, L. ; Zhang, J. ; Halbgebauer, R. ; Mannes, M. ; Boeckers, T. M.DZNE* ; Knöll, B. ; Lien, E. ; Mollnes, T. E. ; Huber-Lang, M. ; Roselli, F. (Last author)DZNE*

2026
Springer International Publishing AG Cham

This record in other databases:    

Please use a persistent id in citations: doi:10.1007/s00011-026-02367-7

Abstract: TBI-polytrauma (P-TBI) is associated with acute neurological deterioration, delirium, and poor prognosis. Systemic inflammatory mediators are thought to amplify the cerebral neuroimmune response, particularly microglial activation, with detrimental consequences.We investigated the roles of complement factor C3 and the TLR co-receptor CD14 in a murine polytrauma model combining mild TBI with femur fracture, blunt thorax trauma, and resuscitated haemorrhagic shock, using mice lacking C3, CD14, or both.P-TBI induced a rapid, brain-wide increase in inflammatory cytokines with region-specific patterns. TNF and CCL2 mRNA were upregulated in microglia in the cortex, hippocampus, and striatum, and this response was abolished in C3-/-CD14-/- mice. Analysis of single knockouts showed that cytokine induction depended on CD14 in the cortex, C3 in the striatum, and both in the hippocampus. In contrast, neither C3 nor CD14 influenced cytokine induction at the cortical lesion site. Interestingly, neuronal cFOS responses showed an inverse regional C3/CD14 dependency compared with inflammatory cytokine responses, with a cortical C3 dependency and striatal CD14 dependency.Thus, C3 and CD14 are dispensable for the acute response at the injury site but differentially regulate microglial and neuronal activation in remote brain regions, representing potential targets to reduce P-TBI-associated encephalopathy.

Keyword(s): Animals (MeSH) ; Mice, Inbred C57BL (MeSH) ; Complement C3: genetics (MeSH) ; Mice, Knockout (MeSH) ; Multiple Trauma: immunology (MeSH) ; Multiple Trauma: genetics (MeSH) ; Lipopolysaccharide Receptors: genetics (MeSH) ; Lipopolysaccharide Receptors: immunology (MeSH) ; Male (MeSH) ; Microglia: metabolism (MeSH) ; Cytokines: genetics (MeSH) ; Cytokines: immunology (MeSH) ; Disease Models, Animal (MeSH) ; Neuroinflammatory Diseases: genetics (MeSH) ; Brain: metabolism (MeSH) ; Mice (MeSH) ; Complement ; Cortex ; Delirium ; Microglia ; Polytrauma ; Striatum ; TNF ; Complement C3 ; Lipopolysaccharide Receptors ; Cd14 protein, mouse ; Cytokines ; C3 protein, mouse

---

Contributing Institute(s):

1. Metabolic Changes in Neurodegeneration (AG Roselli)
2. Translational Protein Biochemistry (AG Böckers)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2026

---

Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---