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 journal › Research article › Contributed › peer-review
Contributors
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 language | English |
|---|---|
| Pages (from-to) | 85-94 |
| Number of pages | 10 |
| Journal | Journal of Neuropathology and Experimental Neurology |
| Volume | 74 |
| Issue number | 1 |
| Publication status | Published - Jan 2015 |
| Peer-reviewed | Yes |
| Externally published | Yes |
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