Role of Adaptor Protein Myeloid Differentiation 88 (MyD88) in Post-Subarachnoid Hemorrhage Inflammation: A Systematic Review

Abstract

Myeloid differentiation 88 (MyD88) is a well-established inflammatory adaptor protein. It is one of the essential downstream proteins of the toll-like receptor 4 (TLR4) signaling pathway. TLRs are pattern recognition receptors that are usually activated by the damage-associated molecular pattern molecules (DAMPs). Sterile inflammation is triggered by the endogenous DAMPs released in response to global cerebral ischemia and from extravasated blood after subarachnoid hemorrhage (SAH). In this review, we highlight the importance of the neuroinflammatory role of the MyD88 in the SAH. We also explore a few possible pharmacological agents that can be used to decrease SAH-associated neuroinflammation by modulating the MyD88 dependent functions. Pharmacological agents such as flavonoids, melatonin, fluoxetine, pentoxifylline and progesterone have been investigated experimentally to reduce the SAH-associated inflammation. Inhibition of the MyD88 not only reduces the expression of pro-inflammatory cytokines, but also potentially inhibits other processes that can augment the SAH associated inflammation. Further investigations are required to translate these findings in the clinical setting.

Keywords: aneurysms; neuro-inflammation; pattern recognition receptors; post-SAH complications; stroke.

Figure 1

Activation of toll-like receptor 4 (TLR4) via various damage-associated molecular pattern molecules (DAMPs) to initiate downstream signaling of the receptor after subarachnoid hemorrhage (SAH). Myleoid Diffrentiation 88 (MyD88) can be inhibited by the small molecular inhibitor, melatonin, fluoxetine and various flavonoids. TNF Receptor associated factor 6 (TRAF6) can be inhibited by the Resveratrol, whereas Desatanib targets the mitogen-activated protein kinase 3 (MAPK 3) pathway. TLR4 pathway is associated with neuronal inflammation, apoptosis and activation of pro-inflammatory cytokines.