Nwafor Divine C, Brichacek Allison L, Mohammad Afroz S, Griffith Jessica, Lucke-Wold Brandon P, Benkovic Stanley A, Geldenhuys Werner J, Lockman Paul R, Brown Candice M
Graduate Programs in Neuroscience, Department of Neuroscience, School of Medicine, Health Sciences Center, West Virginia University, Morgantown, WV, USA.
Department of Neuroscience, School of Medicine, Health Sciences Center, West Virginia University, Morgantown, WV, USA.
J Cent Nerv Syst Dis. 2019 Apr 9;11:1179573519840652. doi: 10.1177/1179573519840652. eCollection 2019.
Sepsis is a systemic inflammatory disease resulting from an infection. This disorder affects 750 000 people annually in the United States and has a 62% rehospitalization rate. Septic symptoms range from typical flu-like symptoms (eg, headache, fever) to a multifactorial syndrome known as sepsis-associated encephalopathy (SAE). Patients with SAE exhibit an acute altered mental status and often have higher mortality and morbidity. In addition, many sepsis survivors are also burdened with long-term cognitive impairment. The mechanisms through which sepsis initiates SAE and promotes long-term cognitive impairment in septic survivors are poorly understood. Due to its unique role as an interface between the brain and the periphery, numerous studies support a regulatory role for the blood-brain barrier (BBB) in the progression of acute and chronic brain dysfunction. In this review, we discuss the current body of literature which supports the BBB as a nexus which integrates signals from the brain and the periphery in sepsis. We highlight key insights on the mechanisms that contribute to the BBB's role in sepsis which include neuroinflammation, increased barrier permeability, immune cell infiltration, mitochondrial dysfunction, and a potential barrier role for tissue non-specific alkaline phosphatase (TNAP). Finally, we address current drug treatments (eg, antimicrobials and intravenous immunoglobulins) for sepsis and their potential outcomes on brain function. A comprehensive understanding of these mechanisms may enable clinicians to target specific aspects of BBB function as a therapeutic tool to limit long-term cognitive impairment in sepsis survivors.
脓毒症是一种由感染引起的全身性炎症性疾病。在美国，这种疾病每年影响75万人，再住院率为62%。脓毒症症状范围从典型的流感样症状（如头痛、发热）到一种称为脓毒症相关脑病（SAE）的多因素综合征。SAE患者表现出急性精神状态改变，通常死亡率和发病率更高。此外，许多脓毒症幸存者还伴有长期认知障碍。脓毒症引发SAE以及导致脓毒症幸存者长期认知障碍的机制尚不清楚。由于其作为大脑与外周之间界面的独特作用，众多研究支持血脑屏障（BBB）在急性和慢性脑功能障碍进展中起调节作用。在本综述中，我们讨论了当前支持BBB作为脓毒症中整合来自大脑和外周信号的枢纽的文献。我们强调了对BBB在脓毒症中作用机制的关键见解，这些机制包括神经炎症、屏障通透性增加、免疫细胞浸润、线粒体功能障碍以及组织非特异性碱性磷酸酶（TNAP）的潜在屏障作用。最后，我们讨论了目前用于治疗脓毒症的药物（如抗菌药物和静脉注射免疫球蛋白）及其对脑功能的潜在影响。对这些机制的全面理解可能使临床医生能够将BBB功能的特定方面作为一种治疗工具，以限制脓毒症幸存者的长期认知障碍。
