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Korean Journal of Pediatrics ; : 686-693, 2007.
Artículo en Inglés | WPRIM | ID: wpr-168239

RESUMEN

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.


Asunto(s)
Animales , Ratas , Hipoxia , Apoptosis , Western Blotting , Lesiones Encefálicas , Encéfalo , Caspasa 3 , Técnicas de Cultivo de Célula , Incubadoras , Modelos Animales , Ácido Micofenólico , Neuronas , Fármacos Neuroprotectores , Oxidorreductasas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa
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