Neurochemical Research

, Volume 38, Issue 4, pp 742–752

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

Original Paper

DOI: 10.1007/s11064-013-0972-9

Cite this article as:
Wang, Y., Li, B., Li, Z. et al. Neurochem Res (2013) 38: 742. doi:10.1007/s11064-013-0972-9

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.

Keywords

Ethyl pyruvateHypoxia–ischemiaOligodendrocyteHypomyelinationInflammationApoptosis

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

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Pediatric Department of Qilu HospitalShandong UniversityJinanChina
  2. 2.The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public HealthShandong University Qilu HospitalJinanChina