Roadmap for Stroke: Challenging the Role of the Neuronal Extracellular Matrix
Stroke is a major challenge in modern medicine and understanding the role of the neuronal extracellular matrix (NECM) in its pathophysiology is fundamental for promoting brain repair. Currently, stroke research is focused on the neurovascular unit (NVU). Impairment of the NVU leads to neuronal loss...
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doaj-8362edd55d7441f0b8de2630f805fe782020-11-25T03:38:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-01217554755410.3390/ijms21207554Roadmap for Stroke: Challenging the Role of the Neuronal Extracellular MatrixCiro De Luca0Assunta Virtuoso1Nicola Maggio2Sara Izzo3Michele Papa4Anna Maria Colangelo5Laboratory of Morphology of Neuronal Network, Department of Public Medicine, University of Campania “Luigi Vanvitelli”, 80138 Napoli, ItalyLaboratory of Morphology of Neuronal Network, Department of Public Medicine, University of Campania “Luigi Vanvitelli”, 80138 Napoli, ItalyDepartment of Neurology and Neurosurgery, Sackler Faculty of Medicine, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, IsraelMultidisciplinary Department of Medical-Surgical and Dental Specialties, Plastic Surgery Unit, University of Campania “Luigi Vanvitelli”, 80138 Napoli, ItalyLaboratory of Morphology of Neuronal Network, Department of Public Medicine, University of Campania “Luigi Vanvitelli”, 80138 Napoli, ItalySYSBIO Centre of Systems Biology ISBE.ITALY, University of Milano-Bicocca, 20126 Milano, ItalyStroke is a major challenge in modern medicine and understanding the role of the neuronal extracellular matrix (NECM) in its pathophysiology is fundamental for promoting brain repair. Currently, stroke research is focused on the neurovascular unit (NVU). Impairment of the NVU leads to neuronal loss through post-ischemic and reperfusion injuries, as well as coagulatory and inflammatory processes. The ictal core is produced in a few minutes by the high metabolic demand of the central nervous system. Uncontrolled or prolonged inflammatory response is characterized by leukocyte infiltration of the injured site that is limited by astroglial reaction. The metabolic failure reshapes the NECM through matrix metalloproteinases (MMPs) and novel deposition of structural proteins continues within months of the acute event. These maladaptive reparative processes are responsible for the neurological clinical phenotype. In this review, we aim to provide a systems biology approach to stroke pathophysiology, relating the injury to the NVU with the pervasive metabolic failure, inflammatory response and modifications of the NECM. The available data will be used to build a protein–protein interaction (PPI) map starting with 38 proteins involved in stroke pathophysiology, taking into account the timeline of damage and the co-expression scores of their RNA patterns The application of the proposed network could lead to a more accurate design of translational experiments aiming at improving both the therapy and the rehabilitation processes.https://www.mdpi.com/1422-0067/21/20/7554strokeneuronal extracellular matrixneurovascular unitmatrix metalloproteinasessystems biologymaladaptive plasticity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ciro De Luca Assunta Virtuoso Nicola Maggio Sara Izzo Michele Papa Anna Maria Colangelo |
spellingShingle |
Ciro De Luca Assunta Virtuoso Nicola Maggio Sara Izzo Michele Papa Anna Maria Colangelo Roadmap for Stroke: Challenging the Role of the Neuronal Extracellular Matrix International Journal of Molecular Sciences stroke neuronal extracellular matrix neurovascular unit matrix metalloproteinases systems biology maladaptive plasticity |
author_facet |
Ciro De Luca Assunta Virtuoso Nicola Maggio Sara Izzo Michele Papa Anna Maria Colangelo |
author_sort |
Ciro De Luca |
title |
Roadmap for Stroke: Challenging the Role of the Neuronal Extracellular Matrix |
title_short |
Roadmap for Stroke: Challenging the Role of the Neuronal Extracellular Matrix |
title_full |
Roadmap for Stroke: Challenging the Role of the Neuronal Extracellular Matrix |
title_fullStr |
Roadmap for Stroke: Challenging the Role of the Neuronal Extracellular Matrix |
title_full_unstemmed |
Roadmap for Stroke: Challenging the Role of the Neuronal Extracellular Matrix |
title_sort |
roadmap for stroke: challenging the role of the neuronal extracellular matrix |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-10-01 |
description |
Stroke is a major challenge in modern medicine and understanding the role of the neuronal extracellular matrix (NECM) in its pathophysiology is fundamental for promoting brain repair. Currently, stroke research is focused on the neurovascular unit (NVU). Impairment of the NVU leads to neuronal loss through post-ischemic and reperfusion injuries, as well as coagulatory and inflammatory processes. The ictal core is produced in a few minutes by the high metabolic demand of the central nervous system. Uncontrolled or prolonged inflammatory response is characterized by leukocyte infiltration of the injured site that is limited by astroglial reaction. The metabolic failure reshapes the NECM through matrix metalloproteinases (MMPs) and novel deposition of structural proteins continues within months of the acute event. These maladaptive reparative processes are responsible for the neurological clinical phenotype. In this review, we aim to provide a systems biology approach to stroke pathophysiology, relating the injury to the NVU with the pervasive metabolic failure, inflammatory response and modifications of the NECM. The available data will be used to build a protein–protein interaction (PPI) map starting with 38 proteins involved in stroke pathophysiology, taking into account the timeline of damage and the co-expression scores of their RNA patterns The application of the proposed network could lead to a more accurate design of translational experiments aiming at improving both the therapy and the rehabilitation processes. |
topic |
stroke neuronal extracellular matrix neurovascular unit matrix metalloproteinases systems biology maladaptive plasticity |
url |
https://www.mdpi.com/1422-0067/21/20/7554 |
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