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首页> 外文期刊>The European Journal of Neuroscience >Traumatic brain injury and obesity induce persistent central insulin resistance
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Traumatic brain injury and obesity induce persistent central insulin resistance

机译:颅脑外伤和肥胖导致持续的中枢胰岛素抵抗

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Traumatic brain injury (TBI)-induced impairments in cerebral energy metabolism impede tissue repair and contribute to delayed functional recovery. Moreover, the transient alteration in brain glucose utilization corresponds to a period of increased vulnerability to the negative effects of a subsequent TBI. In order to better understand the factors contributing to TBI-induced central metabolic dysfunction, we examined the effect of single and repeated TBIs on brain insulin signalling. Here we show that TBI induced acute brain insulin resistance, which resolved within 7days following a single injury but persisted until 28days following repeated injuries. Obesity, which causes brain insulin resistance and neuroinflammation, exacerbated the consequences of TBI. Obese mice that underwent a TBI exhibited a prolonged reduction of Akt (also known as protein kinase B) signalling, exacerbated neuroinflammation (microglial activation), learning and memory deficits, and anxiety-like behaviours. Taken together, the transient changes in brain insulin sensitivity following TBI suggest a reduced capacity of the injured brain to respond to the neuroprotective and anti-inflammatory actions of insulin and Akt signalling, and thus may be a contributing factor for the damaging neuroinflammation and long-lasting deficits that occur following TBI.
机译:创伤性脑损伤(TBI)引起的脑能量代谢障碍阻碍组织修复,并导致功能恢复延迟。而且,脑葡萄糖利用的瞬时改变对应于对随后的TBI的负面影响的脆弱性增加的时期。为了更好地了解导致TBI引起的中枢代谢功能障碍的因素,我们检查了单个TBI和重复TBI对脑胰岛素信号的影响。在这里,我们显示TBI诱导了急性脑胰岛素抵抗,在单次受伤后7天内消失,但一直持续到重复受伤后28天内。肥胖会引起脑胰岛素抵抗和神经炎症,加剧了TBI的后果。进行了TBI的肥胖小鼠表现出Akt(也称为蛋白激酶B)信号转导时间的延长,神经炎症(小胶质细胞激活)加剧,学习和记忆力减退以及焦虑样行为。两者合计,TBI后脑部胰岛素敏感性的短暂变化表明受伤的脑部对胰岛素和Akt信号传导的神经保护和抗炎作用作出反应的能力降低,因此可能是破坏性神经炎症和长时程性TBI后出现的持续赤字。

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