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Combination treatment with ethyl pyruvate and IGF-I exerts neuroprotective effects against brain injury in a rat model of neonatal hypoxic-ischemic encephalopathy

  • Authors:
    • Zhihui Rong
    • Rui Pan
    • Liwen Chang
    • Weihua Lee
  • View Affiliations / Copyright

    Affiliations: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Copyright: © Rong et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 195-203
    |
    Published online on: May 22, 2015
       https://doi.org/10.3892/ijmm.2015.2219
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Abstract

Neonatal hypoxic-ischemic (HI) brain injury causes severe brain damage in newborns. Following HI injury, rapidly accumulating oxidants injure neurons and interrupt ongoing developmental processes. The antioxidant, sodium pyruvate, has been shown to reduce neuronal injury in neonatal rats under conditions of oxygen glucose deprivation (OGD) and HI injury. In this study, we evaluated the effects of ethyl pyruvate (EP) and insulin‑like growth factor‑I (IGF‑I) alone or in combination in a similar setting. For this purpose, we used an in vitro model involving primary neonatal rat cortical neurons subjected to OGD for 2.5 h and an in vivo model involving unilateral carotid ligation in rats on post-natal day 7 with exposure to 8% hypoxia for 2.5 h. The cultured neurons were examined by lactate dehydrogenase (LDH) and cell viability assays. For the in vivo experiments, behavioral development was evaluated by the foot fault test at 4 weeks of recovery. 2,3,5‑Triphenyltetrazolium chloride monohydrate and cresyl violet staining were used to evaluate HI injury. The injured neurons were Fluoro‑Jade B-labeled, new neuroprecursors were double labeled with bromodeoxyuridine (BrdU) and doublecortin, new mature neurons were BrdU-labeled and neuronal nuclei were labeled by immunofluorescence. Under conditions of OGD, the LDH levels increased and neuronal viability decreased. Treatment with 0.5 mM EP or 25 ng/ml IGF‑I protected the neurons (P<0.05), exerting additive effects. Similarly, either the early administration of EP or delayed treatment with IGF‑I protected the neonatal rat brains against HI injury and improved neurological performance and these effects were also additive. This effect may be the result of reduced neuronal injury, and enhanced neurogenesis and maturation. On the whole, our findings demonstrate that the combination of the early administration of EP with delayed treatment with IGF‑I exerts neuroprotective effects against HI injury in neonatal rat brains.
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Copy and paste a formatted citation
Spandidos Publications style
Rong Z, Pan R, Chang L and Lee W: Combination treatment with ethyl pyruvate and IGF-I exerts neuroprotective effects against brain injury in a rat model of neonatal hypoxic-ischemic encephalopathy. Int J Mol Med 36: 195-203, 2015.
APA
Rong, Z., Pan, R., Chang, L., & Lee, W. (2015). Combination treatment with ethyl pyruvate and IGF-I exerts neuroprotective effects against brain injury in a rat model of neonatal hypoxic-ischemic encephalopathy. International Journal of Molecular Medicine, 36, 195-203. https://doi.org/10.3892/ijmm.2015.2219
MLA
Rong, Z., Pan, R., Chang, L., Lee, W."Combination treatment with ethyl pyruvate and IGF-I exerts neuroprotective effects against brain injury in a rat model of neonatal hypoxic-ischemic encephalopathy". International Journal of Molecular Medicine 36.1 (2015): 195-203.
Chicago
Rong, Z., Pan, R., Chang, L., Lee, W."Combination treatment with ethyl pyruvate and IGF-I exerts neuroprotective effects against brain injury in a rat model of neonatal hypoxic-ischemic encephalopathy". International Journal of Molecular Medicine 36, no. 1 (2015): 195-203. https://doi.org/10.3892/ijmm.2015.2219
Copy and paste a formatted citation
x
Spandidos Publications style
Rong Z, Pan R, Chang L and Lee W: Combination treatment with ethyl pyruvate and IGF-I exerts neuroprotective effects against brain injury in a rat model of neonatal hypoxic-ischemic encephalopathy. Int J Mol Med 36: 195-203, 2015.
APA
Rong, Z., Pan, R., Chang, L., & Lee, W. (2015). Combination treatment with ethyl pyruvate and IGF-I exerts neuroprotective effects against brain injury in a rat model of neonatal hypoxic-ischemic encephalopathy. International Journal of Molecular Medicine, 36, 195-203. https://doi.org/10.3892/ijmm.2015.2219
MLA
Rong, Z., Pan, R., Chang, L., Lee, W."Combination treatment with ethyl pyruvate and IGF-I exerts neuroprotective effects against brain injury in a rat model of neonatal hypoxic-ischemic encephalopathy". International Journal of Molecular Medicine 36.1 (2015): 195-203.
Chicago
Rong, Z., Pan, R., Chang, L., Lee, W."Combination treatment with ethyl pyruvate and IGF-I exerts neuroprotective effects against brain injury in a rat model of neonatal hypoxic-ischemic encephalopathy". International Journal of Molecular Medicine 36, no. 1 (2015): 195-203. https://doi.org/10.3892/ijmm.2015.2219
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