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http://dx.doi.org/10.3345/kjp.2008.51.2.170

Neuroprotective effects of geneticin (G418) via apoptosis in perinatal hypoxic-ischemic brain injury  

Ju, Mi (Department of Pediatrics, School of Medicine, Catholic University of Daegu)
Lee, Hyun Ju (Department of Pediatrics, School of Medicine, Catholic University of Daegu)
Lee, Sun Ju (Department of Pediatrics, School of Medicine, DongGuk University)
Seo, Eo Su (Department of Ophthalmology, School of Medicine, DongGuk University)
Park, Hye Jin (Department of Pediatrics, School of Medicine, Catholic University of Daegu)
Lee, Kye Yang (Department of Pediatrics, School of Medicine, Catholic University of Daegu)
Lee, Gyeong Hoon (Department of Pediatrics, School of Medicine, Catholic University of Daegu)
Choi, Eun Jin (Department of Pediatrics, School of Medicine, Catholic University of Daegu)
Kim, Jin Kyung (Department of Pediatrics, School of Medicine, Catholic University of Daegu)
Lee, Jong Won (Department of Biochemistry, School of Medicine, Catholic University of Daegu)
Chung, Hai Lee (Department of Pediatrics, School of Medicine, Catholic University of Daegu)
Kim, Woo Taek (Department of Pediatrics, School of Medicine, Catholic University of Daegu)
Publication Information
Clinical and Experimental Pediatrics / v.51, no.2, 2008 , pp. 170-180 More about this Journal
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.
Keywords
Hypoxic-ischemic brain injury; Anti-apoptosis; Perinatal; Geneticin; G418;
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