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KMID : 1130320070500070686
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Korean Journal of Pediatrics
2007 Volume.50 No. 7 p.686 ~ p.693
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The neuroprotective effect of mycophenolic acid via anti-apoptosis in perinatal hypoxic-ischemic brain injury
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Kim Ji-Young
Park Kwan-Kyu
Kim Woo-Taek
Kim Jin-Kyung
Chung Hai-Lee
Yang Seung-Ho
Kim Ji-Eun
Chang Young-Chae
Cha Sun-Ha
Seo Eok-Su
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Abstract
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Purpose : Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), is a potent inhibitor of inosine-monophosphate dehydrogenase (IMPDH), a new immunosuppressive drug used. It was reported that MPA protected neurons after excitotoxic injury, induced apoptosis in microglial cells. However, the effects of MPA on hypoxic-ischemic (HI) brain injury has not been yet evaluated. Therefore, we examined whether MPA could be neuroprotective in perinatal HI brain injury using Rice-Vannucci model (in vivo) and in rat brain cortical cell culture induced by hypoxia (in vitro).
Methods : Cortical cells were cultured using a 18-day-pregnant Sprague-Dawley (SD) rats and incubated in 1% O2 incubator for hypoxia. MPA (10 microgram/mL) before or after a HI insult was treated. Seven-day-old SD rat pups were subjected to left carotid occlusion followed by 2 hours of hypoxic exposure (8% O2). MPA (10 mg/kg) before or after a HI insult were administrated intraperitoneally. Apoptosis was measured using western blot and real-time PCR for Bcl-2, Bax, caspase-3.
Results : H&E stain revealed increased brain volume in the MPA-treated group in vivo animal model of neonatal HI brain injury. Western blot and real-time PCR showed the expression of caspase-3 and Bax/Bcl-2 were decreased in the MPA-treated group In in vitro and in vivo model of perinatal HI brain injury,
Conclusion : These results may suggest that the administration of MPA before HI insult could significantly protect against perinatal HI brain injury via anti-apoptotic mechanisms, which offers the possibility of MPA application for the treatment of neonatal HI encephalopathy.
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KEYWORD
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Mycophenolic acid, Hypoxic-Ischemic, Apoptosis, Caspase-3, Bax, Bcl-2
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