Sunday, December 23, 2018

Role of immune responses for extracellular matrix remodeling in the ischemic brain

Lots of big words but nothing I could see of use to recovery

Role of immune responses for extracellular matrix remodeling in the ischemic brain



Introduction Ischemic stroke remains a leading cause of death and disability in the adult population. Despite plenty of efforts devoted to understanding and treating the disease, most novel approaches have only a discouragingly limited impact on patients’ wellbeing. 1 We suggest that to improve the translation of scientific advances from bench to bedside, the pathophysiology of ischemic stroke should be investigated from complementary nb points of view. Today, most studies of stroke put the major focus on neuronal plasticity and repair, 2–4 blood–brain barrier (BBB) dysfunction, 5 and neuroinflammation. 6 In this review, we will address the relationship between the immune response and the reorganization of the extracellular matrix (ECM) during the acute and chronic phases of ischemic stroke. Although both aspects have been studied individually, their interaction is rarely considered in both experimental and clinical settings. We propose that the brain’s immune response and ECM regulation should be considered as a functional unit, as first proposed by Schönherr and Hausser, 7 opening new perspectives in stroke treatment. The ECM is a congregation of multiple adhesion molecules, polysaccharides, proteins and proteoglycans arranged three-dimensionally in the extracellular space. During development and adulthood, this complex fulfils various functions, such as regulating cell migration, proliferation, adhesion, differentiation, 8 synaptic plasticity, 9 maintenance of the BBB 10 and tissue architecture, integrity and homeostasis. 11 In the central nervous system (CNS), ECM can be divided into two compartments, the interstitial matrices and basement membranes (BMs). 12 The interstitial matrix is based on diffuse meshworks of hyaluronic acid (HA), which incorporate mainly collagens and proteoglycans. 13 The BMs are associated with the basal portion of cerebral endothelial cells and consist mainly of laminins, collagen IV, nidogens and heparan sulfate proteoglycans.

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