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Roadmap for Stroke: Challenging the Role of the Neuronal Extracellular Matrix

  • De Luca, Ciro1
  • Virtuoso, Assunta1, 2
  • Maggio, Nicola3
  • Izzo, Sara
  • Papa, Michele1,
  • Colangelo, Anna Maria4
  • 1 (A.V.)
  • 2 School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
  • 3 Department of Neurology and the J. Sagol Neuroscience Center, The Chaim Sheba Medical Center, Tel HaShomer, Ramat Gan 5211401, Israel
  • 4 Laboratory of Neuroscience “R. Levi-Montalcini”, Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milano, Italy
Published Article
International Journal of Molecular Sciences
Publication Date
Oct 13, 2020
DOI: 10.3390/ijms21207554
PMID: 33066304
PMCID: PMC7589675
PubMed Central


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.

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