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| Home > Articles > Published articles > Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome |
| Home > Articles > Published articles > Cold stress protein RBM3 responds to hypothermia and is associated with good stroke outcome |
(Instituto de Investigación Sanitaria de Santiago (IDIS)) (Instituto de Investigación Sanitaria de Santiago (IDIS)) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Hospital Universitari de Girona Doctor Josep Trueta) (Instituto de Investigación Sanitaria de Santiago (IDIS)) (Instituto de Investigación Sanitaria de Santiago (IDIS))| Date: | 2020 |
| Abstract: | 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. |
| Grants: | Agencia Estatal de Investigación SAF2017-84267-R Ministerio de Economía y Competitividad RD16/0019 Instituto de Salud Carlos III PI17/00540 Instituto de Salud Carlos III CPII17/00027 Instituto de Salud Carlos III CPII19/00020 Instituto de Salud Carlos III CPD19/00033 European Commission FP7/2007-2013 European Commission 278709 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Hypothermia ; Neuroprotection ; RBM3 ; Stroke ; Translational study |
| Published in: | Brain Communications, Vol. 2 (june 2020) , ISSN 2632-1297 |
