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KMID : 1130320080510020170
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Korean Journal of Pediatrics
2008 Volume.51 No. 2 p.170 ~ p.180
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Neuroprotective effects of geneticin (G418) via apoptosis in perinatal hypoxic-ischemic brain injury
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Ju Mi
Lee Hyun-Ju
Lee Sun-Ju
Seo Eok-Su
Park Hye-Jin
Lee Kye-Hyang
Lee Gyeong-Hun
Choi Eun-Jin
Kim Jin-Kyung
Lee Jong-Won
Chung Hai-Lee
Kim Woo-Taek
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Abstract
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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.(Korean J Pediatr 2008;51:170-180)
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KEYWORD
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Hypoxic-ischemic brain injury, Anti-apoptosis, Perinatal, Geneticin, G418
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