title: Adjuvant granulocyte colony-stimulating factor therapy results in improved spatial learning and stimulates hippocampal neurogenesis in a mouse model of pneumococcal meningitis.
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.
authors.affiliation: From the Department of Neurology, RWTH University Hospital, Aachen (AKS, AR, BF, JBS, SCT); JARA Translational Brain Medicine, Aachen and Jülich (BF, JBS); Department of Anatomy and Cell Biology, RWTH University, Aachen (OB); and Institute of Neuropathology, University Medical Center, Göttingen (SR), Germany.
authors.forename: Anna Kathrin
authors.initials: AK
authors.lastname: Schmidt
authors.forename: Arno
authors.initials: A
authors.lastname: Reich
authors.forename: Björn
authors.initials: B
authors.lastname: Falkenburger
authors.forename: Jörg B
authors.initials: JB
authors.lastname: Schulz
authors.forename: Lars Ove
authors.initials: LO
authors.lastname: Brandenburg
authors.forename: Sandra
authors.initials: S
authors.lastname: Ribes
authors.forename: Simone C
authors.initials: SC
authors.lastname: Tauber
mesh_terms: D053687:Adult Stem Cells / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002443:Ceftriaxone / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008586:Meningitis, Pneumococcal / Q000150:complications* / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D016179:Granulocyte Colony-Stimulating Factor; D002443:Ceftriaxone