title: Intracerebroventricular application of granulocyte colony-stimulating factor after cardiac arrest does not promote beneficial effects on cerebral recovery after cardiac arrest in rats.
abstract: METHODS
  Recent data demonstrated potent neuroprotective effects of growth hormones such as granulocyte colony-stimulating factor (G-CSF) after focal cerebral ischaemia. In order to assess possible effects of intracerebroventricular application of G-CSF on cerebral recovery after cardiac arrest (CA) in rats, neurological testing and histological analyses were performed.
  
  
  METHODS
  After 6 min of electrically induced CA, rats were resuscitated (CPR) and divided into two groups (G-CSF vs. placebo) with two different reperfusion times (7 and 14 days). G-CSF (3.84 microg) or placebo was applied 30 min after restoration of spontaneous circulation (ROSC). At 24h, 3, 7, 10 and 14 days, behavioural neurological testing was done (tape removal test, TRT). Neuronal degeneration of the hippocampal CA-1 sector was analyzed by TUNEL- and Nissl-staining.
  
  
  RESULTS
  Before CA all animals passed the TRT (G-CSF 7 [4-12] s, placebo 9 [6-10] s). After ROSC both groups showed a clear neurological deficit (24h: G-CSF and placebo 180 [180-180] s), that improved with ongoing reperfusion times, without reaching baseline values (14 days: G-CSF 25 [21-59] s, placebo 34 [14-175] s). Survival rates did not differ between the groups. All animals showed massive neurodegeneration histologically without any differences between the groups 7 days after CA (TUNEL-positive: G-CSF 63.2 [53.8-72.1], placebo 72.6 [66.6-82.7]; Nissl-positive: G-CSF 2.5 [1.8-3.4], placebo 2.8 [2.0-5.1]). At 14 days, TUNEL-staining revealed no differences (G-CSF 45.2 [35.0-60.0], placebo 56.0 [37.6-63.4]), while G-CSF treatment led to fewer Nissl-positive neurons (G-CSF 1.5 [1.2-2.2], placebo 3.1 [2.1-4.2]; p=0.011).
  
  
  CONCLUSIONS
  Despite promising experimental data concerning focal cerebral ischaemia, in this model of 6 min of normothermic CA no beneficial effects of G-CSF application could be demonstrated by behavioural testing and histological analyses of the hippocampal CA-1 sector.
authors.affiliation: Department of Anaesthesiology, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany. erik.popp@uni-heidelberg.de
authors.forename: Erik
authors.initials: E
authors.lastname: Popp
authors.forename: Tobias
authors.initials: T
authors.lastname: Rabsahl
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneider
authors.forename: Nicolai
authors.initials: N
authors.lastname: Russ
authors.forename: Fabian
authors.initials: F
authors.lastname: Spöhr
authors.forename: Peter
authors.initials: P
authors.lastname: Vogel
authors.forename: Bernd W
authors.initials: BW
authors.lastname: Böttiger
authors.forename: Peter
authors.initials: P
authors.lastname: Teschendorf
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D016887:Cardiopulmonary Resuscitation; D002404:Catheterization; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006323:Heart Arrest / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D007276:Injections, Intraventricular; D008297:Male; D011597:Psychomotor Performance; D051381:Rats; D011930:Reaction Time / Q000502:physiology; D011994:Recombinant Proteins; D020127:Recovery of Function
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim