| The neuroprotective effect of mycophenolic acid via anti-apoptosis in perinatal hypoxic-ischemic brain injury |
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Ji Young Kim1, Seung Ho Yang1, Sun Hwa Cha1, Ji Yeun Kim2, Young Chae Jang3, Kwan Kyu Park3, Jin Kyung Kim1, Hai Lee Chung1, Eok Su Seo3, Woo Taek 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 |
| 주산기 저산소성 허혈성 뇌손상에서 항세포자멸사를 통한 mycophenolic acid의 신경보호 효과 |
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김지영1, 양승호1, 차선화1, 김지언2, 장영채3, 박관규3, 김진경1, 정혜리1, 서억수3, 김우택1 |
1대구가톨릭대학교 의과대학 소아과학교실
2대구가톨릭대학교 의과대학 신경과학교실
3동국대학교 의과대학 안과학교실 |
Correspondence:
Woo Taek Kim, Email: wootykim@cu.ac.kr
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| 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. |
| Key Words:
Mycophenolic acid, Hypoxia-Ischemia, Apoptosis, Caspase-3, Bax, Bcl-2 |
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