title: Granulocyte colony-stimulating factor does not promote neurogenesis after experimental intracerebral haemorrhage.
abstract: BACKGROUND
  Hematopoietic growth factors have been suggested to induce neuroprotective and regenerative effects in various animal models of cerebral injury. However, the pathways involved remain widely unexplored.
  
  
  OBJECTIVE
  This study aimed to investigate effects of local and systemic administration of granulocyte colony-stimulating factor on brain damage, functional recovery, and cerebral neurogenesis in an intracerebral haemorrhage whole blood injection model in rats.
  
  
  METHODS
  Eight-week-old male Wistar rats (n = 100) underwent induction of striatal intracerebral haemorrhage by autologous whole blood injection or sham procedure and were randomly assigned to either (a) systemic treatment with granulocyte colony-stimulating factor (60 μg/kg) for five-days; (b) single intracerebral injection of granulocyte colony-stimulating factor (60 μg/kg) into the cavity; or (c) application of vehicle for five-days. Bromodeoxyuridine-labelling and immunohistochemistry were used to analyze proliferation and survival of newly born cells in the sub-ventricular zone and the hippocampal dentate gyrus. Moreover, functional deficits and lesion volume were assessed until day 42 after intracerebral haemorrhage.
  
  
  RESULTS
  Differences in lesion size or hemispheric atrophy between granulocyte colony-stimulating factor-treated and control groups did not reach statistical significance. Neither systemic, nor local granulocyte colony-stimulating factor administration induced neurogenesis within the dentate gyrus or the sub-ventricular zone. The survival of newborn cells in these regions was prevented by intracerebral granulocyte colony-stimulating factor application. A subtle benefit in functional recovery at day 14 after intracerebral haemorrhage induction was observed after granulocyte colony-stimulating factor treatment.
  
  
  CONCLUSIONS
  There was a lack of neuroprotective or neuroregenerative effects of granulocyte colony-stimulating factor in the present rodent model of intracerebral haemorrhage. Conflicting results from functional outcome assessment require further research.
authors.affiliation: Department of Neurology, University Medical Center Erlangen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kallmünzer
authors.forename: Miyuki
authors.initials: M
authors.lastname: Tauchi
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Schlachetzki
authors.forename: Kristin
authors.initials: K
authors.lastname: Machold
authors.forename: Ariana
authors.initials: A
authors.lastname: Schmidt
authors.forename: Jürgen
authors.initials: J
authors.lastname: Winkler
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwab
authors.forename: Rainer
authors.initials: R
authors.lastname: Kollmar
mesh_terms: D000818:Animals; D001284:Atrophy; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001973:Bromodeoxyuridine; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D007150:Immunohistochemistry; D008297:Male; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011897:Random Allocation; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D016179:Granulocyte Colony-Stimulating Factor; D001973:Bromodeoxyuridine
keywords: acute stroke therapy; brain bleed; cerebral haemorrhage; neuroprotection; stem cells; stroke