Neuroprotective effects of geneticin (G418) via apoptosis in perinatal hypoxic-ischemic brain injury.
10.3345/kjp.2008.51.2.170
- Author:
Mi JU
1
;
Hyun Ju LEE
;
Sun Ju LEE
;
Eo Su SEO
;
Hye Jin PARK
;
Kye Yang LEE
;
Gyeong Hoon LEE
;
Eun Jin CHOI
;
Jin Kyung KIM
;
Jong Won LEE
;
Hai Lee CHUNG
;
Woo Taek KIM
Author Information
1. Department of Pediatrics, School of Medicine, DongGuk University, Kyeong-Ju, Korea.
- Publication Type:Original Article
- Keywords:
Hypoxic-ischemic brain injury;
Anti-apoptosis;
Perinatal;
Geneticin;
G418
- MeSH:
Animals;
Anoxia;
Anti-Bacterial Agents;
Apoptosis;
Blotting, Western;
Brain;
Brain Injuries;
Breast Neoplasms;
Carotid Artery, Common;
Caspase 3;
Cell Culture Techniques;
Eosine Yellowish-(YS);
Gentamicins;
Hematoxylin;
Humans;
Immunohistochemistry;
In Situ Nick-End Labeling;
Incubators;
Models, Animal;
Neuroprotective Agents;
Rats;
Real-Time Polymerase Chain Reaction
- From:Korean Journal of Pediatrics
2008;51(2):170-180
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Some antibiotics were known to exert neuroprotective effects in the animal model of hypoxic-ischemic (H-I) brain injury, but the mechanism is still unclear. A recent study reported that geneticin (G418), an aminoglycoside antibiotic, increased survival of human breast cancer cells by suppressing apoptosis. We investigated the neuroprotective effects of systemically administrated geneticin via anti-apoptosis following the H-I brain injury METHODS: Seven-day-old Sprague-Dawley rat pups were subjected to unilateral (left) common carotid artery occlusion followed by 2.5 hours of hypoxic exposure and the cortical cell culture of rat brain was done under a hypoxic incubator. Apoptosis was measured in the injured hemispheres 7 days after H-I insult and in the injured cells from hypoxic chamber using morphologic analysis by Terminal dUTP Nick-end Labeling(TUNEL) assay and immunohistochemistry for caspase-3, and cytologic analysis by western blot and real time PCR for bax, bcl-2, and caspase-3. RESULTS: The gross appearance and hematoxylin and eosin stain revealed increased brain volume in the geneticin-treated animal model of perinatal H-I brain injury. The TUNEL assay revealed decreased apoptotic cells after administration of geneticin in the cell culture model of anoxia. Immunohistochemistry showed decreased caspase-3 expression in geneticin-treated cortical cell culture. Western blot and real-time PCR showed decreased caspase-3 expression and decreased ratio of Bax/Bcl-2 expression in geneticin-treated animal model. CONCLUSION: Geneticin appears to exert a neuroprotective effect against perinatal H-I brain injury at least via anti-apoptosis. However, more experiments are needed in order to demonstrate the usefulness of geneticin as a preventive and rescue treatment for H-I brain injuries of neonatal brain.
