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Neuroprotective effects of geneticin (G418) via apoptosis in perinatal hypoxic-ischemic brain injury / 소아과
Korean Journal of Pediatrics ; : 170-180, 2008.
Article in English | WPRIM | ID: wpr-218626
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.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Brain / Brain Injuries / Breast Neoplasms / Immunohistochemistry / Gentamicins / Blotting, Western / Carotid Artery, Common / Apoptosis / Eosine Yellowish-(YS) / Neuroprotective Agents Limits: Animals / Humans Language: English Journal: Korean Journal of Pediatrics Year: 2008 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Brain / Brain Injuries / Breast Neoplasms / Immunohistochemistry / Gentamicins / Blotting, Western / Carotid Artery, Common / Apoptosis / Eosine Yellowish-(YS) / Neuroprotective Agents Limits: Animals / Humans Language: English Journal: Korean Journal of Pediatrics Year: 2008 Type: Article