Adjuvant granulocyte colony-stimulating factor therapy results in improved spatial learning and stimulates hippocampal neurogenesis in a mouse model of pneumococcal meningitis

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Anna Kathrin Schmidt - (Author)
  • Arno Reich - (Author)
  • Björn Falkenburger - , University Hospital Aachen, JARA-Brain Institute I Brain structure function relationships (Author)
  • Jörg B Schulz - (Author)
  • Lars Ove Brandenburg - (Author)
  • Sandra Ribes - (Author)
  • Simone C Tauber - (Author)

Abstract

Despite the development of new antibiotic agents, mortality of pneumococcal meningitis remains high. In addition, meningitis results in severe long-term morbidity, most prominently cognitive deficits. Granulocyte colony-stimulating factor (G-CSF) stimulates proliferation and differentiation of hematopoietic progenitor cells and increases the number of circulating neutrophil granulocytes. This study investigated the effect of adjuvant G-CSF treatment on cognitive function after pneumococcal meningitis. C57BL/6 mice were infected by subarachnoid injection of Streptococcus pneumoniae serotype 3 and treated with ceftriaxone and G-CSF subcutaneously or ceftriaxone alone for 5 days. Clinical scores, motor performance, and mortality during bacterial meningitis were unaffected by adjuvant G-CSF treatment. No effect of G-CSF treatment on production of proinflammatory cytokines or activation of microglia or astrocytes was observed. The G-CSF treatment did, however, result in hippocampal neurogenesis and improved spatial learning performance 6 weeks after meningitis. These results suggest that G-CSF might offer a new adjuvant therapeutic approach in bacterial meningitis to reduce long-term cognitive deficits.

Details

Original languageEnglish
Pages (from-to)85-94
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Volume74
Issue number1
Publication statusPublished - Jan 2015
Peer-reviewedYes
Externally publishedYes

External IDs

Scopus 84920267379
ORCID /0000-0002-2387-526X/work/176343369

Keywords

Keywords

  • Adult Stem Cells/drug effects, Animals, Anti-Bacterial Agents/therapeutic use, Ceftriaxone/therapeutic use, Cell Differentiation/drug effects, Cognition Disorders/drug therapy, Cytokines/genetics, Disease Models, Animal, Granulocyte Colony-Stimulating Factor/therapeutic use, Hippocampus/drug effects, Male, Maze Learning/drug effects, Meningitis, Pneumococcal/complications, Mice, Mice, Inbred C57BL, Motor Activity/drug effects, Neurogenesis/drug effects, Phosphorylation/drug effects, Streptococcus pneumoniae/pathogenicity, Time Factors