title: Improvement of hypoxia-ischemia-induced white matter injury in immature rat brain by ethyl pyruvate.
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.
authors.affiliation: Pediatric Department of Qilu Hospital, Shandong University, Wenhuaxi Road 44, Jinan, 250012 Shandong Province, China.
authors.forename: Yingyan
authors.initials: Y
authors.lastname: Wang
authors.forename: Baomin
authors.initials: B
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Shanying
authors.initials: S
authors.lastname: Huang
authors.forename: Jiwen
authors.initials: J
authors.lastname: Wang
authors.forename: Ruopeng
authors.initials: R
authors.lastname: Sun
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000187:drug effects; D053148:Caspase 3 / Q000096:biosynthesis; D002552:Cerebral Ventricles / Q000473:pathology; D016207:Cytokines / Q000037:antagonists & inhibitors; D004660:Encephalitis / Q000517:prevention & control; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009836:Oligodendroglia / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011773:Pyruvates / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011773:Pyruvates; D051028:bcl-2-Associated X Protein; C046522:ethyl pyruvate; D053148:Caspase 3