Neuroprotective effects of

Background: Methods: Male Sprague Dawley rats were intracerebroventricularly administered with 1% dimethyl sulfoxide 25 min before cerebral ischemia and subsequently intraperitoneally administered 0.25 g/kg (DO + TM-0.25 g), 0.5 g/kg (DO + TM-0.5 g), or 1 g/kg (DO + TM-1 g) of the TM extract after cerebral ischemia onset. Results: DO + TM-0.5 g and DO + TM-1 g treatments downregulated the following: phospho-c-Jun N-terminal kinase (p-JNK)/JNK, tumor necrosis factor (TNF) receptor-associated factor 3 (TRAF3), TRAF3-interacting JNK-activating modulator (T3JAM), p-nuclear factor-kappa B p65 (p-NF-κB p65)/NF-κB p65, ionized calcium-binding adapter molecule 1 (Iba1), CD86, TNF-α, interleukin (IL)-1β, and IL-6 expression and toll-like receptor 4 (TLR4)/Iba1, CD86/Iba1, and p-NF-κB p65/Iba1 coexpression. These treatments also upregulated IL-10, nerve growth factor, and vascular endothelial growth factor A expression and YM-1/2/Iba1 and IL-10/neuronal nuclei coexpression in the cortical ischemic rim. The JNK inhibitor SP600125 exerted similar treatment effects as the DO + TM-0.5 g and DO + TM-1 g treatments. Conclusion: DO + TM-0.5 g and DO + TM-1 g/kg treatments attenuate cerebral infarction by inhibiting JNK-mediated signaling. TM likely exerts the neuroprotective effects of promoting M1 to M2 microglial polarization by inhibiting JNK/TLR4/T3JAM/NF-κB-mediated signaling in the cortical ischemic rim 2 days after transient cerebral ischemia.