Microglial polarization in TBI: Signaling pathways and influencing pharmaceuticals

Abstract

Traumatic brain injury (TBI) is a serious disease that threatens life and health of people. It poses a great economic burden on the healthcare system. Thus, seeking effective therapy to cure a patient with TBI is a matter of great urgency. Microglia are macrophages in the central nervous system (CNS) and play an important role in neuroinflammation. When TBI occurs, the human body environment changes dramatically and microglia polarize to one of two different phenotypes: M1 and M2. M1 microglia play a role in promoting the development of inflammation, while M2 microglia play a role in inhibiting inflammation. How to regulate the polarization direction of microglia is of great significance for the treatment of patients with TBI. The polarization of microglia involves many cellular signal transduction pathways, such as the TLR-4/NF-κB, JAK/STAT, HMGB1, MAPK, and PPAR-γ pathways. These provide a theoretical basis for us to seek therapeutic drugs for the patient with TBI. There are several drugs that target these pathways, including fingolimod, minocycline, Tak-242 and erythropoietin (EPO), and CSF-1. In this study, we will review signaling pathways involved in microglial polarization and medications that influence this process.

Lysophosphatidic Acid Receptor 1 Plays a Pathogenic Role in Permanent Brain Ischemic Stroke by Modulating Neuroinflammatory Responses

“…This notion was further supported by findings from the current study to analyse LPA 1 -dependent effector pathways such as NF-κB, MAPKs, and PI3K/Akt. In general, activation of MAPKs and NF-κB is associated with M1 polarization ( Lawrence, 2009 ; Li et al ., 2022b ). In contrast, activation of PI3K/Akt is associated with M2 polarization ( Vergadi et al ., 2017 ).…”

Cerebral Hemodynamic Changes Associated with Neuroinflammation under Seawater Immersion Hypothermia

“…A series of secondary injuries occur after TBI, and neuroin ammation is one of the most intensively studied categories. Microglia are essential in regulating central nervous system homeostasis and are mainly involved in the regulation of neuroin ammation [29]. Microglia exist in various activation states after TBI and perform the following two functions: rst, microglia differentiate toward a pro-in ammatory (M1) phenotype, producing pro-in ammatory cytokines such as TNF-α, IL-1β, and IL-12 and expressing high levels of inducible NO synthase [30,31].…”

Reactive gliosis in traumatic brain injury: a comprehensive review

“…Upon ligand binding (e.g., cytokines) to a specific receptor, JAK is recruited in close proximity to the receptor and is activated by phosphorylation. Consequently, downstream substrate STAT is also activated by phosphorylation, causing STAT dimerization and its translocation from the cytosol to the nucleus, where STAT regulates the expression of the related genes ( Rane and Reddy, 2000 ; Xin et al, 2020 ; Jain et al, 2021 ; Li et al, 2022b ). The JAK/STAT pathway is involved in cell proliferation, differentiation, apoptosis, and mediating innate and adaptive immunity ( Rane and Reddy, 2000 ; Xin et al, 2020 ; Jain et al, 2021 ; Li et al, 2022a ).…”