Insulin-like growth factor-1 lowers spreading depression susceptibility and reduces oxidative stress.
Insulin-like growth factor-1 lowers spreading depression susceptibility and reduces oxidative stress.
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DOI：
10.1111/j.1471-4159.2012.07763.x
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发表时间：
2012-07
影响因子：
4.7
通讯作者：
Kraig RP
中科院分区：
文献类型：
--
作者：
Grinberg YY;van Drongelen W;Kraig RP
扩散性抑郁(SD)可能是引起偏头痛先兆甚至偏头痛的原因，它是由广泛的和不受约束的神经元过度兴奋引起的。偏头痛和引发癫痫的过度兴奋性可能是相互关联的，其中包括氧化应激(OS)。环境浓缩(EE)可减少癫痫发作，并可减少偏头痛。EE的神经保护作用与胰岛素样生长因子-1(IGF-1)有关。因此，我们使用大鼠海马片培养来询问IGF-1是否可以减轻引发SD的超兴奋性。我们证明IGF-1显著降低SD易感性和相关的OS。我们模拟SD大鼠的OS，观察到IGF-1消除了OS的过度兴奋性。应用抗氧化剂显著降低SD的易感性，抗氧化剂与IGF-1联合应用不产生相加效应，而氧化剂显著增加SD，这种作用被IGF-1消除。此外，IGF-1显著降低了基线OS，尽管似乎矛盾地增加了CA3的爆发。这些结果表明，IGF-1使内源性抗氧化剂增加到足以缓冲SD的OS的水平。胰岛素同样可以减轻SD的敏感性，但需要的剂量要大得多。由于大脑IGF-1随着EE的增加而增加，并且像胰岛素一样，独立地作为EE模拟物发挥作用，我们建议EE模拟物是治疗SD和偏头痛的新来源。
Spreading depression (SD), the likely cause of migraine aura and perhaps migraine, is triggered by widespread and unfettered neuronal hyperexcitability. Migraine and the initiating hyperexcitability of seizure, which involve oxidative stress (OS), are likely interrelated. Environmental enrichment (EE) decreases seizure and can reduce migraine. EE's well-characterized neuroprotective effect involves insulin-like growth factor-1 (IGF-1). Accordingly, we asked if IGF-1 could mitigate the hyperexcitability that initiates SD using rat hippocampal slice cultures. We demonstrate that IGF-1 significantly decreased SD susceptibility and related OS. We mimicked OS of SD and observed that IGF-1 abolished hyperexcitability from OS. Application of an antioxidant significantly decreased SD susceptibility and co-administration of an antioxidant with IGF-1 produced no additive effect, whereas an oxidizer significantly increased SD, and this effect was abrogated by IGF-1. Moreover, IGF-1 significantly decreased baseline OS, despite seemingly paradoxically increasing CA3 bursting. These results suggest that IGF-1 increased endogenous antioxidants to levels sufficient to buffer against the OS of SD. Insulin similarly mitigated SD susceptibility, but required a far greater dose. Since brain IGF-1 increases with EE, and, like insulin, independently functions as an EE mimetic, we suggest that EE mimetics are a novel source of therapeutics for SD, and by extension, migraine.
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影响因子：
--
作者：
Craft, Suzanne;Baker, Laura D.;Montine, Thomas J.;Minoshima, Satoshi;Watson, G. Stennis;Claxton, Amy;Arbuckle, Matthew;Callaghan, Maureen;Tsai, Elaine;Plymate, Stephen R.;Green, Pattie S.;Leverenz, James;Cross, Donna;Gerton, Brooke
通讯作者：
Gerton, Brooke
影响因子：
4.2
作者：
Kumar A;Rani A;Tchigranova O;Lee WH;Foster TC
通讯作者：
Foster TC
影响因子：
2.5
作者：
Darabaneanu, S.;Overath, C. H.;Weisser, B.
通讯作者：
Weisser, B.
影响因子：
1.7
作者：
de la Vega, AG;Buño, W;Torres-Aleman, I
通讯作者：
Torres-Aleman, I
影响因子：
6.4
作者：
Herring, Arne;Blome, Mareike;Keyvani, Kathy
通讯作者：
Keyvani, Kathy