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Improvement of Hypoxia–Ischemia-Induced White Matter Injury in Immature Rat Brain by Ethyl Pyruvate

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Abstract

Ethyl pyruvate (EP) has been reported to be neuroprotective in several models of brain injury, yet its influence on periventricular leukomalacia still remains elusive. Here we investigated whether repeated administration of EP could protect against white matter injury after hypoxia–ischemia (HI) (right common carotid artery ligation and 6 % O2 for 60 min) in post-natal 3 day rat pups. EP was injected (50 mg/kg, intraperitoneally) 10 min, 1 and 24 h after HI insult. Treatment with EP significantly reduced HI-induced ventricular enlargement, loss of developing oligodendrocytes, and hypomyelination. We further demonstrated a marked inhibitory effect of EP on inflammatory responses, as indicated by the decreased number of activated microglia and astrocytes and the reduced release of proinflammatory cytokines. Moreover, EP down-regulated the expression of cleaved caspase-3 and Bax, and up-regulated Bcl-2 expression after HI exposure. In conclusion, our results demonstrated that EP was able to provide potent protection on white matter injury through blocking the cerebral inflammatory responses and modulating the apoptotic death program of oligodendrocytes, indicating a potential neuroprotective agent in neonatal brain injury.

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Abbreviations

EP:

Ethyl pyruvate

GFAP:

Glial fibrillary acidic protein

HI:

Hypoxia–ischemia

Hpf:

High power field

Iba-1:

Ionized calcium binding adapter molecule-1

MBP:

Myelin basic protein

OL:

Oligodendrocyte

PVL:

Periventricular leukomalacia

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Acknowledgments

This study was supported by Science Foundation of Chinese Ministry of Education (20080422057). We are grateful to all the members of the author’s laboratory for their contributions to this work.

Conflict of interest

The authors declare no conflict of interest exists.

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Authors and Affiliations

  1. Pediatric Department of Qilu Hospital, Shandong University, Wenhuaxi Road 44, Jinan, 250012, Shandong Province, China

    Yingyan Wang, Baomin Li, Zhen Li, Jiwen Wang & Ruopeng Sun

  2. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, Shandong Province, China

    Shanying Huang

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  1. Yingyan Wang
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  2. Baomin Li
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  3. Zhen Li
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Correspondence to Jiwen Wang or Ruopeng Sun.

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Wang, Y., Li, B., Li, Z. et al. Improvement of Hypoxia–Ischemia-Induced White Matter Injury in Immature Rat Brain by Ethyl Pyruvate. Neurochem Res 38, 742–752 (2013). https://doi.org/10.1007/s11064-013-0972-9

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  • DOI: https://doi.org/10.1007/s11064-013-0972-9

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