Table 1.

Brief overview of the association between Toll-like receptors and cerebral vascular diseases

CVDs
TLRs	AIS	ICH	SAH	CVST
TLR2	Moderator for leukocytes and microglial infiltration and neuronal death [78, 79]	–		Activated in antiphospholipid syndrome [80]
TLR3	Neuroprotective and anti-inflammatory effects on SD-induced neuroinflammation [63] Ischemic tolerance induction by TLR3 ligand poly I:C preconditioning through type I IFN signaling [81]	Neuroprotective and anti-inflammatory effects on SD-induced neuroinflammation [21, 82]
TLR4	Neuroprotective effect by preconditioning through suppression of cytotoxic TNFα, increasing IRFs and production of type I interferons [78, 79] Induction and evolution of atherosclerosis through NF-κB pathway that produce inflammation [78, 79]	Increasing levels of inflammatory factors, DNA damage, and neuronal degeneration in perihematomal region [82]	Activation by Heme product through the MyD88 and TRIF pathways [83]	Activated in antiphospholipid syndrome [80]
TLR7	Neuroprotective effect by preconditioning with TLR7 ligand, gardiquimod, reduction in infarct size, and a better functional outcome independent of TNFα and dependent on interferon [84]	–
TLR8	Activation causes worsening of ischemic brain injury [85]	–		–
TLR9	Neuroprotective effect by preconditioning through suppression of cytotoxic TNFα, increasing IRFs, and production of type I interferons [20]	–		Deletion is associated with larger venous thrombosis and increased leukocyte infiltration [80]

AIS acute ischemic stroke, APS antiphospholipid syndrome, ICH intracerebral hemorrhage, CVD cerebral vascular disease, CVST cerebral venous sinus thrombosis, SAH subarachnoid hemorrhage, SD spreading depolarization, TNF tissue necrosis factor, IFNA interferon-α/β receptor, TLR Toll-like receptor