Potential role of biomarkers of the toll-like receptor 4 signaling pathway in subarachnoid hemorrhage

Abstract

Subarachnoid hemorrhage (SAH) is often accompanied by severe nerve injury. In survivors of primary bleeding, secondary brain injury may cause additional harm. The main mechanism of secondary brain injury is the inflammatory reaction of brain parenchyma after bleeding. The overactivation of the brain’s innate immune system can disrupt homeostasis, the release of inflammatory factors, and the apoptosis of nerve cells. Studies have shown that the toll-like receptor (TLR) 4 signaling pathway plays a key role in the pathophysiological process of acute brain injuries such as SAH. TLR4 mainly exists on the surface of microglia, an important cell type in the brain. During an intracranial aneurysm rupture, many endogenous ligands with damage-related molecular patterns, such as hemoglobin and fibrinogen, activate TLR4, and the resulting inflammatory response and tissue damage may further activate TLR4. Components of the signaling pathway, such as TLR4 ligands, the receptor itself, and inflammatory cytokines, are used biomarkers that can elucidate the inflammatory state after SAH. Other constituents of the TLR4 pathway that indicate inflammation include protein complexes, such as the NLRP3 inflammasome, and receptors, such as TREM1. This review introduces the mechanism of the TLR4 signaling pathway in the neuroinflammatory reaction after SAH and discusses the use of TLR4 signaling pathway components as biomarkers of neuroinflammation, providing new ideas for the prevention and treatment of secondary nerve injury after SAH.