Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome.
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.
['Ávila-Gómez|Paulo|P|', 'Vieites-Prado|Alba|A|', 'Dopico-López|Antonio|A|', 'Bashir|Saima|S|', 'Fernández-Susavila|Héctor|H|', 'Gubern|Carme|C|', 'Pérez-Mato|María|M|', 'Correa-Paz|Clara|C|', 'Iglesias-Rey|Ramón|R|', 'Sobrino|Tomás|T|', 'Bustamante|Alejandro|A|', 'Wellmann|Sven|S|', 'Montaner|Joan|J|', 'Serena|Joaquín|J|', 'Castillo|José|J|', 'Hervella|Pablo|P|0000-0003-1249-6333', 'Campos|Francisco|F|']
RBM3 hypothermia stroke neuroprotection translational study