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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/31614


    標題: Gamma-Secretase Inhibitors Attenuate Neurotrauma and Neurogenic Acute Lung Injury in Rats by Rescuing the Accumulation of Hypertrophic Microglia
    作者: Lin, Hung-Jung
    Hsu, Chien-Chin
    Chio, Chung-Ching
    Tian, Yu-Feng
    Lin, Mao-Tsun
    Lin, Ting-Wei
    Chang, Chih-Hsien
    Chang, Ching-Ping
    貢獻者: 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
    關鍵字: Traumatic brain injury
    gamma-secretase
    Neurogenic acute lung injury
    Microglia
    日期: 2017
    上傳時間: 2018-11-30 15:50:18 (UTC+8)
    出版者: Karger
    摘要: 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
    關聯: Cellular Physiology and Biochemistry, v.44, n.5, pp.1726-1740
    Appears in Collections:[保健營養系(所) ] 期刊論文

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