Granulocyte Stimulating Factor Attenuates Hypoxic-ischemic Brain Injury by Inhibiting Apoptosis in Neonatal Rats.
10.3349/ymj.2008.49.5.836
- Author:
Bong Rim KIM
1
;
Jae Won SHIM
;
Dong Kyung SUNG
;
Sung Shin KIM
;
Ga Won JEON
;
Myo Jing KIM
;
Yun Sil CHANG
;
Won Soon PARK
;
Eung Sang CHOI
Author Information
1. Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. wonspark@skku.edu
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Granulocyte stimulating factor;
neuroprotective agents;
hypoxia-ischemia;
newborn;
apoptosis
- MeSH:
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
- From:Yonsei Medical Journal
2008;49(5):836-842
- CountryRepublic of Korea
- Language:English
-
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).
