Modulation of cholinergic pathways and inflammatory mediators in blast-induced traumatic brain injury

被引：39

作者：

Valiyaveettil, Manojkumar ^{[1
]}

Alamneh, Yonas A. ^{[1
]}

Miller, Stacey-Ann ^{[2
]}

Hammamieh, Rasha ^{[2
]}

Arun, Peethambaran ^{[1
]}

Wang, Ying ^{[1
]}

Wei, Yanling ^{[1
]}

Oguntayo, Samuel ^{[1
]}

Long, Joseph B. ^{[1
]}

Nambiar, Madhusoodana P. ^{[1
]}

机构：

[1] Walter Reed Army Inst Res, Blast Induced Neurotrauma Branch, Ctr Mil Psychiat & Neurosci, Silver Spring, MD 20910 USA

[2] USA, Ctr Environm Hlth Res, Med Res & Mat Command, Ft Detrick, MD 21702 USA

来源：

CHEMICO-BIOLOGICAL INTERACTIONS | 2013年 / 203卷 / 01期

关键词：

Repeated blast exposure; Cholinergic pathway; Inflammation; Acetylcholinisterase; Micro RNA; Traumatic brain injury; ANTIINFLAMMATORY PATHWAY; ACETYLCHOLINESTERASE ACTIVITY; LUNG TRAUMA; STRESS; MODEL; BLOOD; MICRORNAS; EXPOSURE; MOUSE; RATS;

D O I：

10.1016/j.cbi.2012.10.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cholinergic activity has been recognized as a major regulatory component of stress responses after traumatic brain injury (TB!). Centrally acting acetylcholinesterase (AChE) inhibitors are also being considered as potential therapeutic candidates against TBI mediated cognitive impairments. We have evaluated the expression of molecules involved in cholinergic and inflammatory pathways in various regions of brain after repeated blast exposures in mice. Isoflurane anesthetized C57BL/6J mice were restrained and placed in a prone position transverse to the direction of the shockwaves and exposed to three 20.6 psi blast overpressures with 1-30 min intervals. Brains were collected at the 6 h time point after the last blast exposure and subjected to cDNA microarray and microRNA analysis. cDNA microarray analysis showed significant changes in the expression of cholinergic (muscarinic and nicotinic) and gammaaminobutyric acid and glutamate receptors in the midbrain region along with significant changes in multiple genes involved in inflammatory pathways in various regions of the brain. MicroRNA analysis of cerebellum revealed differential expression of miR-132 and 183, which are linked to cholinergic anti-inflammatory signaling, after blast exposure. Changes in the expression of myeloperoxidase in the cerebellum were confirmed by Western blotting. These results indicate that early pathologic progression of blast TBI involves dysregulation of cholinergic and inflammatory pathways related genes. Acute changes in molecules involved in the modulation of cholinergic and inflammatory pathways after blast TBI can cause long-term central and peripheral pathophysiological changes. (C) 2012 Published by Elsevier Ireland Ltd.

引用

页码：371 / 375

页数：5

共 31 条

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