Korean J Pediatr.  2007 Jul;50(7):686-693. 10.3345/kjp.2007.50.7.686.

The neuroprotective effect of mycophenolic acid via anti-apoptosis in perinatal hypoxic-ischemic brain injury

• Kim JY
• Yang SH
• Cha SH
• Kim JY
• Jang YC
• Park KK
• Kim JK
• Chung HL
• Seo ES
• Kim WT

• KMID: 2278466
• DOI: http://doi.org/10.3345/kjp.2007.50.7.686

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.

Keyword

Mycophenolic acid; Hypoxia-Ischemia; Apoptosis; Caspase-3; Bax; Bcl-2

MeSH Terms

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
Caspase 3
Mycophenolic Acid
Neuroprotective Agents
Oxidoreductases