The neuroprotective effect of mycophenolic acid via anti-apoptosis in perinatal hypoxic-ischemic brain injury.
10.3345/kjp.2007.50.7.686
- Author:
Ji Young KIM
1
;
Seung Ho YANG
;
Sun Hwa CHA
;
Ji Yeun KIM
;
Young Chae JANG
;
Kwan Kyu PARK
;
Jin Kyung KIM
;
Hai Lee CHUNG
;
Eok Su SEO
;
Woo Taek KIM
Author Information
1. Department of Pediatrics, School of Medicine, Catholic University of Daegu, Daegu, Korea. wootykim@cu.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Mycophenolic acid;
Hypoxia-Ischemia;
Apoptosis;
Caspase-3;
Bax;
Bcl-2
- MeSH:
Animals;
Anoxia;
Apoptosis;
Blotting, Western;
Brain Injuries*;
Brain*;
Caspase 3;
Cell Culture Techniques;
Incubators;
Models, Animal;
Mycophenolic Acid*;
Neurons;
Neuroprotective Agents*;
Oxidoreductases;
Rats;
Rats, Sprague-Dawley;
Real-Time Polymerase Chain Reaction
- From:Korean Journal of Pediatrics
2007;50(7):686-693
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
