Stanzione Rosita, Forte Maurizio, Cotugno Maria, Bianchi Franca, Marchitti Simona, Rubattu Speranza
IRCCS Neuromed, Pozzilli, IS, Italy.
Department of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
Cell Mol Neurobiol. 2022 Apr;42(3):545-556. doi: 10.1007/s10571-020-00966-4. Epub 2020 Sep 29.
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.
中风是全球死亡和残疾的主要原因。缺血性中风（IS）的发病机制涉及多种机制。炎症和免疫过程在体外和动物模型中均显示出其作用，并在人类中得到证实。IS引发即刻炎症反应，涉及复杂的细胞和分子机制。先天免疫和适应性免疫系统的所有组成部分都参与了缺血级联反应的多个步骤。在早期，炎症和免疫机制导致脑组织损伤，而在后期，它们参与组织修复过程。特别是，损伤相关分子模式（DAMPs）对于促进血脑屏障通透性改变、白细胞浸润、组织水肿和脑损伤似乎至关重要。相反，调节性T淋巴细胞（Tregs）的激活具有保护作用。识别属于炎症和免疫反应的特定细胞/分子成分，这些成分有助于脑缺血损伤和组织重塑，为设计适当的治疗策略提供了优势。在本文中，我们将概述IS中炎症和免疫过程的相关知识，特别关注DAMPs和白细胞浸润的作用。我们将讨论在IS临床前模型和人类中获得的证据。将重点介绍有助于开发新型治疗方法的主要分子机制。将实验结果转化为人类疾病的治疗仍然是一个艰难的步骤。需要进一步研究来填补现有空白。
