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Matrix metalloproteinases and ADAMs in stroke

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Abstract

Stroke is a leading cause of death and disability worldwide. However, after years of in-depth research, the pathophysiology of stroke is still not fully understood. Increasing evidence shows that matrix metalloproteinases (MMPs) and “a disintegrin and metalloproteinase” (ADAMs) participate in the neuro-inflammatory cascade that is triggered during stroke but also in recovery phases of the disease. This review covers the involvement of these proteins in brain injury following cerebral ischemia which has been widely studied in recent years, with efforts to modulate this group of proteins in neuroprotective therapies, together with their implication in neurorepair mechanisms. Moreover, the review also discusses the role of these proteins in specific forms of neurovascular disease, such as small vessel diseases and intracerebral hemorrhage. Finally, the potential use of MMPs and ADAMs as guiding biomarkers of brain injury and repair for decision-making in cases of stroke is also discussed.

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Abbreviations

ADAM:

A disintegrin and metalloproteinase

ADAMTS:

A disintegrin and metalloproteinase with thrombospondin motifs

BBB:

Blood–brain barrier

CAA:

Cerebral amyloid angiopathy

COX:

Cyclooxygenase

CSF:

Cerebrospinal fluid

CSPGs:

Chondroitin sulfate-bearing proteoglycans

CT:

Computed tomography

EPCs:

Endothelial progenitor cells

ICH:

Intracerebral hemorrhage

MMP:

Matrix metalloproteinase

MT:

Mechanical thrombectomy

OGD:

Oxygen–glucose–deprivation

PHE:

Perihematomal edema

PNN:

Perineuronal net

SAH:

Subarachnoid hemorrhage

SIVD:

Subcortical ischemic vascular disease or vascular cognitive impairment

SVD:

Small vessel diseases

TACE:

Tumor necrosis factor alpha converting enzyme

TIMP:

Tissue inhibitor of MMPs

TNFa:

Tumor necrosis factor alpha

tPA:

Tissue-plasminogen activator

VWF:

Von Willebrand factor

WMH:

White matter hyperintensity

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Acknowledgements

L. R. holds a predoctoral fellowship (IFI17/00012), A. B. is supported by the Juan Rodes program (JR16/00008), and A. R. and M. H.-G. are supported by the Miguel Servet program (CPII15/00003 and CPII17/00010, respectively), all from the Instituto de Salud Carlos III. This research has been funded with the research Grants PI16/00981, PI15/00354 and RETICS INVICTUS RD16/0019/0021 from the Instituto de Salud Carlos III, Spain, co-financed by the European Regional Development Fund and SGR 2017/1427 from the Generalitat de Catalunya (AGAUR).

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  1. Neurovascular Research Laboratory, Vall d’Hebron Institute of Research, Universitat Autònoma de Barcelona, Passeig de la Vall d’Hebron, 119-129, 08035, Barcelona, Spain

    Joan Montaner, Laura Ramiro, Alba Simats, Mar Hernández-Guillamon, Pilar Delgado, Alejandro Bustamante & Anna Rosell

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Montaner, J., Ramiro, L., Simats, A. et al. Matrix metalloproteinases and ADAMs in stroke. Cell. Mol. Life Sci. 76, 3117–3140 (2019). https://doi.org/10.1007/s00018-019-03175-5

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