All issues > Volume 50(7); 2007

Original Article

Korean J Pediatr. 2007;50(7):686-693. Published online July 15, 2007.

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

Ji Young JY Kim¹, Seung Ho SH Yang¹, Sun Hwa SH Cha¹, Ji Yeun JY Kim², Young Chae YC Jang³, Kwan Kyu KK Park³, Jin Kyung JK Kim¹, Hai Lee HL Chung¹, Eok Su ES Seo³, Woo Taek WT Kim¹

¹Department of Pediatrics, School of Medicine, Catholic University of Daegu, Daegu, S. Korea
²Department of Neurology, School of Medicine, Catholic University of Daegu, Daegu, S. Korea
³Department of Opthalmology, College of Medicine, Dongguk University, Kyungju, S. Korea

Correspondence Woo Taek WT Kim ,Email: wootykim@cu.ac.kr

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 g/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.

Keywords :Mycophenolic acid, Hypoxia-Ischemia, Apoptosis, Caspase-3, Bax, Bcl-2