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

Korean Journal of Pediatrics 2008;51(2):170-180.
Published online February 15, 2008.
Neuroprotective effects of geneticin (G418) via apoptosis in perinatal hypoxic-ischemic brain injury
Mi Ju1, Hyun Ju Lee1, Sun Ju Lee2, Eo Su Seo3, Hye Jin Park1, Kye Yang Lee1, Gyeong Hoon Lee1, Eun Jin Choi1, Jin Kyung Kim1, Jong Won Lee4, Hai Lee Chung1, Woo Taek Kim1
1Department of Pediatrics, Catholic University of Daegu, Daegu, Korea
2Department of Pediatrics, School of Medicine, DongGuk University, Kyeong-Ju, Korea
3Department of Ophthalmology, School of Medicine, DongGuk University, Kyeong-Ju, Korea
4Department of Biochemistry, School of Medicine, Catholic University of Daegu, Daegu, Korea
주산기 저산소성 허혈성 뇌손상에서 항고사를통한 geneticin (G418)의 신경보호 효과
주미1, 이현주1, 이선주2, 서억수3, 박혜진1, 이계향1, 이경훈1, 최은진1, 김진경1, 이종원4, 정혜리1, 김우택1
1대구가톨릭대학교 의과대학 소아과학교실
2동국대학교 의과대학 소아과학교실
3동국대학교 의과대학 안과학교실
4대구가톨릭대학교 의과대학 생화학교실
Woo Taek Kim, Email: wootykim@cu.ac.kr
: 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
: 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.
: 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.
: 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.
Key Words: Hypoxic-ischemic brain injury, Anti-apoptosis, Perinatal, Geneticin, G418

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