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

J Neuropathol Exp Neurol. 2015 Jan;74(1):85-94. doi: 10.1097/NEN.0000000000000152.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Anti-Bacterial Agents
  • Cytokines
  • Granulocyte Colony-Stimulating Factor
  • Ceftriaxone