The role of the Toll-like receptor family in stroke: functions, mechanisms and therapeutic targets

Mar 9, 2026Brain research bulletin

How Toll-like receptors influence stroke: their roles, workings, and possible treatments

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Abstract

Toll-like receptors (TLRs) play a complex role in stroke, contributing to both inflammatory brain injury and potential neuroprotection.

TLRs are essential for recognizing specific patterns associated with pathogens and tissue damage.
Their activation can lead to increased inflammation in the brain during a stroke.
Certain signaling pathways, like MyD88 and TRIF, are critical in mediating TLR functions.
Dietary components and exosome communication may regulate TLR activity through the gut-brain axis.
Strategies to target TLRs could balance their harmful and protective effects in stroke.
The review evaluates the potential of TLR agonists, antagonists, and combination therapies for therapeutic use.

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Toll-like receptors (TLRs) are pivotal pattern recognition receptors in the innate immune system, primarily responsible for detecting pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). This review comprehensively examines the dual role of TLRs in stroke pathophysiology, wherein they exacerbate inflammatory brain injury yet also harbor neuroprotective potential. We delve into the core signaling mechanisms, specifically the MyD88-dependent and TRIF-dependent pathways, and evaluate their relevance as therapeutic targets. Furthermore, we synthesize emerging insights into novel regulators of TLR activity, including dietary components via the gut-brain axis and exosome-mediated intercellular communication. By integrating evidence from other inflammatory diseases, we propose targeted strategies to balance the detrimental and beneficial effects of TLR activation. The therapeutic potential of TLR agonists, antagonists, and combination therapies is critically appraised. Finally, we delineate future research priorities, including the optimization of TLR modulation, exploration of combination therapies, and cross-disease mechanistic studies, to fully realize the translational promise of TLRs in stroke therapy.

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The role of the Toll-like receptor family in stroke: functions, mechanisms and therapeutic targets

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