Role of DAMPs and of Leukocytes Infiltration in Ischemic Stroke: Insights from Animal Models and Translation to the Huma
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REVIEW PAPER
Role of DAMPs and of Leukocytes Infiltration in Ischemic Stroke: Insights from Animal Models and Translation to the Human Disease Rosita Stanzione1 · Maurizio Forte1 · Maria Cotugno1 · Franca Bianchi1 · Simona Marchitti1 · Speranza Rubattu1,2 Received: 28 April 2020 / Accepted: 22 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Stroke is a leading cause of death and disability worldwide. Several mechanisms are involved in the pathogenesis of ischemic stroke (IS). The contributory role of the inflammatory and immunity processes was demonstrated both in vitro and in animal models, and was confirmed in humans. IS evokes an immediate inflammatory response that involves complex cellular and molecular mechanisms. All components of the innate and adaptive immunity systems are involved in several steps of the ischemic cascade. In the early phase, inflammatory and immune mechanisms contribute to the brain tissue damage, whereas, in the late phase, they participate to the tissue repair processes. In particular, damage-associated molecular patterns (DAMPs) appear critical for the promotion of altered blood brain barrier permeability, leukocytes infiltration, tissue edema and brain injury. Conversely, the activation of regulatory T lymphocytes (Tregs) plays protective effects. The identification of specific cellular/molecular elements belonging to the inflammatory and immune responses, contributing to the brain ischemic injury and tissue remodeling, offers the advantage to design adequate therapeutic strategies. In this article, we will present an overview of the knowledge on inflammatory and immunity processes in IS, with a particular focus on the role of DAMPs and leukocytes infiltration. We will discuss evidence obtained in preclinical models of IS and in humans. The main molecular mechanisms useful for the development of novel therapeutic approaches will be highlighted. The translation of experimental findings to the human disease is still a difficult step to pursue. Further investigations are required to fill up the existing gaps. Keywords Ischemic stroke · Inflammation · Immunity · MCAO · Damps · Leukocytes
Introduction Stroke is the second-leading cause of mortality after ischemic heart disease and one of the main causes of disability worldwide (Favate and Younger 2016; Benjamin et al. 2019). In most cases (85–87%), stroke is of ischemic type (ischemic stroke, IS) and is due to cerebral vessel occlusion by an embolus or a thrombus. The remaining type of Rosita Stanzione and Maurizio Forte have equally contributed. * Rosita Stanzione [email protected] * Speranza Rubattu [email protected] 1
IRCCS Neuromed, Pozzilli, IS, Italy
Department of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, Rome, Italy
2
stroke is hemorrhagic and occurs following the rupture of a cerebral vessel. In both situations, the blood flow is reduced or completely interrupted causing a failure of oxygen and
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