Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome.
Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome.
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DOI：
10.1093/braincomms/fcaa078
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发表时间：
2020
影响因子：
4.8
通讯作者：
Campos F
中科院分区：
文献类型：
--
作者：
Ávila-Gómez P;Vieites-Prado A;Dopico-López A;Bashir S;Fernández-Susavila H;Gubern C;Pérez-Mato M;Correa-Paz C;Iglesias-Rey R;Sobrino T;Bustamante A;Wellmann S;Montaner J;Serena J;Castillo J;Hervella P;Campos F
RNA 结合基序蛋白 3 是低温的分子标志物，已被证明在神经退行性疾病模型中具有神经保护作用。然而，其与众所周知的低温治疗缺血性中风的疗效之间的关系尚未得到研究。在这项工作中，在遭受全身性和局灶性脑低温的缺血动物模型中研究了RNA结合基序蛋白3的表达，特别是RNA结合基序蛋白3沉默和过度表达对缺血性病变的影响。此外，在两个独立的急性缺血性中风患者队列中评估了 RNA 结合基序蛋白 3 水平与体温和临床结果的关联 (n = 215)；这些水平也在第三组 31 名患者中进行了测定，这些患者来自对缺血性中风进行冷却治疗的 III 期 EuroHYP-1 试验。临床前数据证实，在全身性和局灶性低温的缺血动物中，脑RNA结合基序蛋白3的水平有所增加；在经历局灶性脑低温的动物的冷却半球中，这种增加选择性较高，从而证实了低温对RNA结合基序蛋白3表达的直接影响，而缺血脑区域中RNA结合基序蛋白3的上调导致功能恢复。临床上，前两个队列中体温<37.5°C的患者在24小时时具有较高的RNA结合基序蛋白3值，并且在缺血性中风后3个月时具有良好的结果，而降温的第三组中的RNA结合基序蛋白3水平往往超过安慰剂治疗的患者。这些结果使 RNA 结合基序蛋白 3 成为与缺血性中风中低温效应相关的分子标记，并表明其作为有前途的保护靶点的潜在应用。低温是中风的有效神经保护治疗方法。我们已经证明，在缺血和中风患者的动物模型中，RBM3 的表达在低温治疗下增加。这些结果证明 RBM3 作为有前景的缺血保护靶点的潜在应用。
RNA-binding motif protein 3 is a molecular marker of hypothermia that has proved neuroprotective in neurodegenerative disease models. However, its relationship to the well-recognized therapeutic effect of hypothermia in ischaemic stroke had not been studied. In this work, the expression of RNA-binding motif protein 3 was investigated in ischaemic animal models subjected to systemic and focal brain hypothermia, specifically the effects of RNA-binding motif protein 3 silencing and overexpression on ischaemic lesions. Moreover, the association of RNA-binding motif protein 3 levels with body temperature and clinical outcome was evaluated in two independent cohorts of acute ischaemic stroke patients (n = 215); these levels were also determined in a third cohort of 31 patients derived from the phase III EuroHYP-1 trial of therapeutic cooling in ischaemic stroke. The preclinical data confirmed the increase of brain RNA-binding motif protein 3 levels in ischaemic animals subjected to systemic and focal hypothermia; this increase was selectively higher in the cooled hemisphere of animals undergoing focal brain hypothermia, thus confirming the direct effect of hypothermia on RNA-binding motif protein 3 expression, while RNA-binding motif protein 3 up-regulation in ischaemic brain regions led to functional recovery. Clinically, patients with body temperature <37.5°C in the first two cohorts had higher RNA-binding motif protein 3 values at 24 h and good outcome at 3 months post-ischaemic stroke, while RNA-binding motif protein 3 levels in the cooled third cohort tended to exceed those in placebo-treated patients. These results make RNA-binding motif protein 3 a molecular marker associated with the effect of hypothermia in ischaemic stroke and suggest its potential application as a promising protective target. Hypothermia is an effective neuroprotective treatment in stroke. We have demonstrated that the expression of RBM3 is increased under hypothermia treatment in animal models of ischaemia and stroke patients. These results evidence the potential application of RBM3 as a promising protective target against ischaemia.
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DOI：
10.12659/msm.905314
发表时间：
2017-12-21
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Ye F;Jin P;Cai X;Cai P;Cai H
通讯作者：
Cai H
影响因子：
16.6
作者：
Zhu, Xinzhou;Yan, Jingyi;Wellmann, Sven
通讯作者：
Wellmann, Sven
影响因子：
8.3
作者：
Vieites-Prado, Alba;Iglesias-Rey, Ramon;Campos, Francisco
通讯作者：
Campos, Francisco
影响因子：
3.7
作者：
Pilotte J;Dupont-Versteegden EE;Vanderklish PW
通讯作者：
Vanderklish PW
影响因子：
2
作者：
Jang, Ho Hee;Lee, Hae Na;Lee, Won-Suk
通讯作者：
Lee, Won-Suk