Review of Neurofilaments as Biomarkers in Sepsis-Associated Encephalopathy

Abstract

Sepsis is a common and fatal disease, especially in critically ill patients. Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction with acute altered consciousness, permanent cognitive impairment, and even coma, accompanied by sepsis, without direct central nervous system infection. When managing SAE, early identification and quantification of axonal damage facilitate faster and more accurate diagnosis and prognosis. Although no specific markers for SAE have been identified, several biomarkers have been proposed. Neurofilament light chain (NFL) is a highly expressed cytoskeletal component of neurofilament (NF) proteins that can be found in blood and cerebrospinal fluid (CSF) after exposure to axonal injury. NFs can be used as diagnostic and prognostic biomarkers for sepsis-related brain injury. Phosphorylation of NFs contributes to the maturation and stabilization of cytoskeletal structures, especially axons, and facilitates axonal transport, including mitochondrial transport and energy transport. The stability of NF proteins can be assessed by monitoring the expression of NF genes. Furthermore, phosphorylation levels of NFs can be monitored to determine mitochondrial axonal transport associated with cellular energy metabolism at distal axons to assess progression during SAE treatment. This paper provides new insights into the biological characteristics, detection techniques, and scientific achievements of NFs, and discusses the underlying mechanisms and future research directions of NFs in SAE.

Graphical Abstract

Keywords:

• neurofilament light chain
• phosphorylated neurofilaments
• cognitive dysfunction
• mitochondria
• axonal transport

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This study was supported by the Department of Finance of Jilin Province (Award Number: 2019SCZT053 | Recipient: Jingxiao Zhang), the Department of Finance of Jilin Province (Award Number: 2019SCZT022 | Recipient: Yongjie Yin), and the Science and Technology Department of Jilin Province (Award Number:3D5212814429| Recipient: Yongjie Yin).