The regulatory role of Toll-like receptors after ischemic stroke: neurosteroids as TLR modulators with the focus on TLR2/4

Tajalli-Nezhad, Saeedeh; Karimian, Mohammad; Beyer, Cordian; Atlasi, Mohammad Ali; Azami Tameh, Abolfazl

The regulatory role of Toll-like receptors after ischemic stroke: neurosteroids as TLR modulators with the focus on TLR2/4

2019

Tajalli-Nezhad, Saeedeh | Karimian, Mohammad | Beyer, Cordian | Atlasi, Mohammad Ali | Azami Tameh, Abolfazl

Ischemic stroke is the most common cerebrovascular disease and considered as a worldwide leading cause of death. After cerebral ischemia, different pathophysiological processes including neuroinflammation, invasion and aggregation of inflammatory cells and up-regulation of cytokines occur simultaneously. In this respect, Toll-like receptors (TLRs) are the first identified important mediators for the activation of the innate immune system and are widely expressed in glial cells and neurons following brain trauma. TLRs are also able to interact with endogenous and exogenous molecules released during ischemia and can increase tissue damage. Particularly, TLR2 and TLR4 activate different downstream inflammatory signaling pathways. In addition, TLR signaling can alternatively play a role for endogenous neuroprotection. In this review, the gene and protein structures, common genetic polymorphisms of TLR2 and TLR4, TLR-related molecular pathways and their putative role after ischemic stroke are delineated. Furthermore, the relationship between neurosteroids and TLRs as neuroprotective mechanism is highlighted in the context of brain ischemia.

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