Progress in Research on TLR4-Mediated Inflammatory Response Mechanisms in Brain Injury after Subarachnoid Hemorrhage

Abstract

Subarachnoid hemorrhage (SAH) is one of the common clinical neurological emergencies. Its incidence accounts for about 5–9% of cerebral stroke patients. Even surviving patients often suffer from severe adverse prognoses such as hemiplegia, aphasia, cognitive dysfunction and even death. Inflammatory response plays an important role during early nerve injury in SAH. Toll-like receptors (TLRs), pattern recognition receptors, are important components of the body’s innate immune system, and they are usually activated by damage-associated molecular pattern molecules. Studies have shown that with TLR 4 as an essential member of the TLRs family, the inflammatory transduction pathway mediated by it plays a vital role in brain injury after SAH. After SAH occurrence, large amounts of blood enter the subarachnoid space. This can produce massive damage-associated molecular pattern molecules that bind to TLR4, which activates inflammatory response and causes early brain injury, thus resulting in serious adverse prognoses. In this paper, the process in research on TLR4-mediated inflammatory response mechanism in brain injury after SAH was reviewed to provide a new thought for clinical treatment.

Pterostilbene as a Therapeutic Alternative for Central Nervous System Disorders: A Review of the Current Status and Perspectives

“…In addition to ischemic stroke, subarachnoid hemorrhage (SAH) is a fatal subtype of hemorrhagic stroke with a fatality rate of 20–30% and an incidence of 5–9% of cases of stroke. Even those who do survive frequently have serious prognoses of hemiplegia, aphasia, cognitive impairment, or even death, which has a significant negative impact on patient quality of life and places a significant burden of care on society. , The prognosis of SAH following therapy is still poor, and early brain injury (EBI), which occurs 72 h after SAH, is now thought to be a major contributing factor. The processes and pathological alterations linked to EBI include neuroinflammation, oxidative stress, and BBB disruption. , The NLRP3 inflammasome, which is linked to associated specklike protein (ASC) and caspase proteases, recruits and activates caspase-1, which causes pro-IL-1β and pro-IL-18 cleavage and maturation, thereby mediating inflammation.…”

“…Even those who do survive frequently have serious prognoses of hemiplegia, aphasia, cognitive impairment, or even death, which has a significant negative impact on patient quality of life and places a significant burden of care on society. 128,129 The prognosis of SAH following therapy is still poor, and early brain injury (EBI), which occurs 72 h after SAH, is now thought to be a major contributing factor. The processes and pathological alterations linked to EBI include neuroinflammation, oxidative stress, and BBB disruption.…”

Bone-Marrow-Derived Mesenchymal Stem Cells Attenuate Behavioral and Cognitive Dysfunction after Subarachnoid Hemorrhage via HMGB1–RAGE Axis Mediation

“…The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/life13040881/s1, Figure S1: Experimental design of the study; Figure S2: Representative tracing images of NOR tests including training and memory tasks before SAH induction (A) and quantification of recognition in percentages (B,C); Table S1: Sequence of all primers used for qRT-PCR analysis; Figure S3: Raw data of Western blotting. References [39][40][41][42][43][44][45]…”

The association between TLRs and clinical outcome in intracerebral hemorrhage

“…In ammatory cells are the main effectors of in ammation following cerebrovascular diseases. Toll-like receptors (TLRs) are a large family of evolutionarily conserved pattern recognition receptors that recognize pathogen-associated molecular patterns [7][8][9]. TLRs mediate frontline defenses in the central nervous system by not only identifying invading pathogens outside the cell but also by recognizing intracellular pathogens captured in endosomes or lysosomes [10][11].…”

“…Activation of TLRs on immune cells by pathogens can induce innate immunity, and they exert a critical in ammatory function [10][11]. Activation of in ammatory cells in response to cerebrovascular diseases is associated with the signi cant induction of several TLRs, especially TLR2 and TLR4, which are considered to mediate the in ammatory reaction involved in the pathophysiological processes [7][8][9][10][11]. In models of ICH, hemoglobin triggered TLR2/TLR4 heterodimer formation in a MyD88-dependent manner initiates in ammatory injury [12].…”