Yonsei Med J.  2008 Oct;49(5):836-842. 10.3349/ymj.2008.49.5.836.

Granulocyte Stimulating Factor Attenuates Hypoxic-ischemic Brain Injury by Inhibiting Apoptosis in Neonatal Rats

Affiliations
  • 1Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. wonspark@skku.edu
  • 2Department of Pediatrics, Hanil General Hospital, Seoul, Korea.
  • 3Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 4Department of Pediatrics, Samsung Biomedical Research Institute, Seoul, Korea.
  • 5Department of Pediatrics, Buchon Sunchonhyang Hospital, Sunchonhyang University, Buchon, Korea.
  • 6Department of Pediatrics, Young San Hospital, Chung-Ang University, Seoul, Korea.

Abstract

PURPOSE
This study was undertaken to determine the neuroprotective effect of granulocyte stimulating factor (G-CSF) on neonatal hypoxic-ischemic brain injury. MATERIALS AND METHODS: Seven-day-old male newborn rat pups were subjected to 110 minutes of 8% oxygen following a unilateral carotid artery ligation. Apoptosis was identified by performing terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and flow cytometry with a combination of fluorescinated annexin V and propidium iodide (PI) and JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide). The extent of cerebral infarction was evaluated at 2 weeks after recovery. RESULTS: With a single dose (50microgram/kg) of G-CSF treatment immediately after hypoxic-ischemic insult, hypoxia-ischemia induced increase in TUNEL-positive cells, annexinV+/PI- and JC-1 positive apoptotic cells in the ipsilateral cerebral cortex was significantly reduced at 24 hours, measured by flow cytometry, and the extent of cerebral infarction at 2 weeks after recovery was also significantly attenuated compared to the hypoxia-ischemia control group. CONCLUSION: Our data suggest that G-CSF is neuroprotective by inhibiting apoptosis, thereby reducing the ensuing cerebral infarction in a newborn rat pup model of cerebral hypoxia-ischemia (HI).

Keyword

Granulocyte stimulating factor; neuroprotective agents; hypoxia-ischemia; newborn; apoptosis

MeSH Terms

Animals
Apoptosis/*drug effects
Brain/pathology
Cerebral Infarction/pathology/prevention & control
Flow Cytometry
Granulocyte Colony-Stimulating Factor/*pharmacology/therapeutic use
Hypoxia-Ischemia, Brain/*drug therapy/pathology
In Situ Nick-End Labeling
Male
Organ Size
Protective Agents/*pharmacology/therapeutic use
Rats
Rats, Sprague-Dawley
Weight Gain
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