Gamma-Secretase Inhibitors Attenuate Neurotrauma and Neurogenic Acute Lung Injury in Rats by Rescuing the Accumulation of Hypertrophic Microglia

doi:10.1159/000485778

CNU IR > Pharmacy and Science > Dept. of Health and Nutrition (including master's program) > Periodical Articles > Item 310902800/31614

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Title:	Gamma-Secretase Inhibitors Attenuate Neurotrauma and Neurogenic Acute Lung Injury in Rats by Rescuing the Accumulation of Hypertrophic Microglia
Authors:	Lin, Hung-Jung Hsu, Chien-Chin Chio, Chung-Ching Tian, Yu-Feng Lin, Mao-Tsun Lin, Ting-Wei Chang, Chih-Hsien Chang, Ching-Ping
Contributors:	Southern Taiwan Univ Sci & Technol, Dept Biotechnol Chi Mei Med Ctr, Dept Emergency Med Chi Mei Med Ctr, Dept Surg Chia Nan Univ Pharm & Sci, Dept Hlth & Nutr Chi Mei Med Ctr, Dept Med Res Cheng Kung Univ, Sch Med, Dept Med Taipei Med Univ, PhD Program Neural Regenerat Med
Keywords:	Traumatic brain injury gamma-secretase Neurogenic acute lung injury Microglia
Date:	2017
Issue Date:	2018-11-30 15:50:18 (UTC+8)
Publisher:	Karger
Abstract:	Background/Aims: In response to traumatic brain injury (TBI), activated microglia exhibit changes in their morphology from the resting ramified phenotype toward the activated hypertrophic or amoeboid phenotype. Here, we provide the first description of the mechanism underlying the neuroprotective effects of gamma-secretase inhibitors on TBI outcomes in rats. Methods: The neuroprotective effects of gamma-secretase inhibitors such as LY411575 or CHF5074 on TBI-induced neurotoxicity were analysed using a neurological motor function evaluation, cerebral contusion assay, immunohistochemical staining for microglia phenotypes, lung injury score and Evans Blue dye extravasation assay of brain and lung oedema. Results: Hypertrophic or amoeboid microglia accumulated in the injured cortex, the blood-brain-barrier was disrupted and neurological deficits and acute lung injury were observed 4 days after TBI in adult rats. However, a subcutaneous injection of LY411575 (5 mg/kg) or CHF5074 (30 mg/kg) immediately after TBI and once daily for 3 consecutive days post-TBI significantly attenutaed the accumulation of hypertrophic microglia in the injured brain, neurological injury, and neurogenic acute lung injury. Conclusion: Gamma-secretase inhibitors attenuated neurotrauma and neurogenic acute lung injury in rats by reducing the accumulation of hypertrophic microglia in the vicinity of the lesion. (c) 2017 The Author(s) Published by S. Karger AG, Basel
Relation:	Cellular Physiology and Biochemistry, v.44, n.5, pp.1726-1740
Appears in Collections:	[Dept. of Health and Nutrition (including master's program)] Periodical Articles

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