Modulation of cholinergic pathways and inflammatory mediators in blast-induced traumatic brain injury
| Autor: | Yanling Wei, Joseph B. Long, Samuel Oguntayo, Yonas Alamneh, Rasha Hammamieh, Stacey-Ann Miller, Manojkumar Valiyaveettil, Peethambaran Arun, Madhusoodana P. Nambiar, Ying Wang |
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| Rok vydání: | 2013 |
| Předmět: |
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Pathology medicine.medical_specialty Traumatic brain injury Gene Expression Inflammation Biology GPI-Linked Proteins Toxicology Mice chemistry.chemical_compound Blast Injuries Cerebellum Muscarinic acetylcholine receptor medicine Animals Tissue Distribution Microarray analysis techniques Glutamate receptor Brain General Medicine medicine.disease Acetylcholinesterase Acetylcholine Mice Inbred C57BL MicroRNAs Nicotinic agonist chemistry Brain Injuries Disease Progression Cholinergic Inflammation Mediators medicine.symptom Neuroscience Signal Transduction |
| Zdroj: | Chemico-Biological Interactions. 203:371-375 |
| ISSN: | 0009-2797 |
| DOI: | 10.1016/j.cbi.2012.10.022 |
| Popis: | Cholinergic activity has been recognized as a major regulatory component of stress responses after traumatic brain injury (TBI). 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 6h 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. |
| Databáze: | OpenAIRE |
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