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Eur J Pharmacol. 2014 Apr 5;728:93-9. doi: 10.1016/j.ejphar.2014.01.066. Epub 2014 Feb 7.

Hyperbaric oxygen enlarges the area of brain damage in MCAO rats by blocking autophagy via ERK1/2 activation.

Author information

1
Department of Pathophysiology, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, Jilin 130021, China.
2
School of Public Health, Jilin University, Changchun, China.
3
First Hospital, Jilin University, Changchun, China.
4
Department of Pathophysiology, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, Jilin 130021, China. Electronic address: bingjinli@hotmail.com.
5
Department of Pathophysiology, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, Jilin 130021, China. Electronic address: sunlk@jlu.edu.cn.

Abstract

Hyperbaric oxygen (HBO) is emerging as a therapy for brain ischemia, although its benefits are still debated. The present study aimed to investigate the effect of HBO on brain damage in a rat model of transient focal cerebral ischemia and its underlying mechanism of action. Male Wistar rats, which had suffered 1.5h of transient middle cerebral artery occlusion (tMCAO) and had a Longa's neuron score of 3, were given pure oxygen at 3.0 atm absolute, for 60 min after the third hour of reperfusion. After 24h of reperfusion, rat brains were removed and studied. 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin and eosin staining revealed that the infarct ratio in the HBO group increased remarkably when compared with the MCAO group. Up-regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) activation was detected in the HBO group because of reactive oxygen species (ROS) generation. Autophagy appeared to be obstructed in the HBO group. Administration of the ERK1/2 inhibitor U0126 decreased the infarct ratio and improved protein clearance by autophagy in the HBO group. Collectively, these results suggest that HBO enlarges the area of brain damage via reactive oxygen species-induced activation of ERK1/2, which interrupts autophagy flux.

KEYWORDS:

Autophagy; Extracellular signal-regulated kinase 1/2; Hyperbaric oxygen; Middle cerebral artery occlusion

PMID:
24512724
DOI:
10.1016/j.ejphar.2014.01.066
[Indexed for MEDLINE]
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