Insulin-like growth factor-1 (IGF-1) is a naturally occurring neurotrophic factor that plays an important role in promoting cell proliferation and differentiation during normal brain development and maturation. The present review examines recent evidence that endogenous IGF-1 also plays a significant role in recovery from insults such as hypoxia-ischemia and that giving additional exogenous IGF-1 can actively ameliorate damage. It is now well established that neurons and other cell types die many hours or even days after initial injury due to activation of programmed cell death pathways. IGF-1 and its binding proteins and receptors are intensely induced within damaged brain regions following brain injury, suggesting a possible a role for IGF-1 in brain recovery. Exogenous administration of IGF-1 within a few hours after brain injury is now known to be protective in both gray and white matter and leads to improved somatic function. In contrast, pre-treatment is ineffective, likely reflecting limited intracerebral penetration of IGF-1 into the uninjured brain. The neuroprotective effects of IGF-1 are mediated by IGF-1 receptors and its binding proteins and are specific to particular cellular phenotypes and brain regions. The window of opportunity for treatment with IGF-1 is limited to a few hours after normothermic brain injury, reflecting its specific actions on early, intracellular events in the apoptotic cascade. However, injury-associated mild post-hypoxic hypothermia, which delays the development of cell death, can shift and dramatically extend the window of opportunity for delayed treatment with IGF-1. Such a combined approach is likely to be essential for any clinical treatment.

中文翻译：

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胰岛素样生长因子-1和缺血性脑损伤。

胰岛素样生长因子-1（IGF-1）是一种天然存在的神经营养因子，在正常的大脑发育和成熟过程中，在促进细胞增殖和分化中起着重要作用。本综述检查了最近的证据，即内源性IGF-1在从缺氧缺血等损伤中恢复中也起着重要作用，并且给予其他外源性IGF-1可以积极改善损伤。现在已经确定，由于程序性细胞死亡途径的激活，神经元和其他细胞类型在初始损伤后许多小时甚至几天后死亡。IGF-1及其结合蛋白和受体在脑损伤后在受损的大脑区域中被强烈诱导，表明IGF-1在脑恢复中可能发挥作用。现在已知在脑损伤后数小时内外源给予IGF-1对灰色和白色物质均具有保护作用，并可改善体细胞功能。相反，预处理是无效的，可能反映了IGF-1进入未受伤的大脑的局限性脑内渗透。IGF-1的神经保护作用是由IGF-1受体及其结合蛋白介导的，并且对特定的细胞表型和大脑区域具有特异性。在正常体温的脑损伤后数小时内，使用IGF-1进行治疗的机会之窗受到限制，这反映了其对凋亡级联反应中早期细胞内事件的特定作用。但是，与损伤相关的轻度低氧后低温治疗会延迟细胞死亡的发生，可以改变并显着延长IGF-1延迟治疗的机会之窗。这种组合方法对于任何临床治疗都可能是必不可少的。