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Neural Regen Res. 2017 Feb;12(2):193-196. doi: 10.4103/1673-5374.200795.

Toll-like receptor 4 as a possible therapeutic target for delayed brain injuries after aneurysmal subarachnoid hemorrhage.

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1
Department of Neurosurgery, Mie University Graduate School of Medicine, Tsu, Japan.

Abstract

Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage (SAH), and Toll-like receptor (TLR) 4 may be an important therapeutic target for post-SAH neuroinflammation. Of the TLR family members, TLR4 is expressed in various cell types in the central nervous system, and is unique in that it can signal through both the myeloid differentiation primary-response protein 88-dependent and the toll receptor associated activator of interferon-dependent cascades to coordinate the maximal inflammatory response. TLR4 can be activated by many endogenous ligands having damage-associated molecular patterns including heme and fibrinogen at the rupture of an intracranial aneurysm, and the resultant inflammatory reaction and thereby tissue damages may furthermore activate TLR4. It is widely accepted that the excreted products of TLR4 signaling alter neuronal functions. Previous studies have focused on the pathway through nuclear factor (NF)-κB signaling among TLR4 signaling pathways as to the development of early brain injury (EBI) such as neuronal apoptosis and blood-brain barrier disruption, and cerebral vasospasm. However, many findings suggest that both pathways via NF-κB and mitogen-activated protein kinases may be involved in EBI and cerebral vasospasm development. To overcome EBI and cerebral vasospasm is important to improve outcomes after SAH, because both EBI and vasopasm are responsible for delayed brain injuries or delayed cerebral ischemia, the most important preventable cause of poor outcomes after SAH. Increasing evidence has shown that TLR4 signaling plays an important role in SAH-induced brain injuries. Better understanding of the roles of TLR4 signaling in SAH will facilitate development of new treatments.

KEYWORDS:

Toll-like receptor 4; cerebral aneurysm; cerebral vasospasm; delayed brain injury; delayed cerebral ischemia; early brain injury; inflammation; subarachnoid hemorrhage

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