(Ba,Ca)(Ti,Sn)O(3)-based piezoelectric ceramics promotes neuroprotection by regulating microglial IL-6/JAK2/STAT3 signaling pathway.

OBJECTIVE: To investigate whether (Ba,Ca)(Ti,Sn)O(3)-based piezoelectric ceramics (BCTS) provide neuroprotection by inhibiting the IL-6/JAK2/STAT3 signaling pathway in microglia. METHODS: BCTS surface morphology and elemental distribution were analyzed using Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectroscopy (EDX), phase composition was determined via X-ray diffraction (XRD), and hydrophilicity was measured through contact angle analysis. Immunofluorescence (IF), Western blot, and ELISA were employed to evaluate the expression of microglial markers and inflammatory factors in the BV2 injury model and in spinal cord injury rats. Behavioral tests were conducted to evaluate motor function recovery in spinal cord injury rats. PC12 cells were cultured with BCTS-CM (supernatant from BCTS-treated BV2 cells) to assess the IL-6/JAK2/STAT3 signaling pathway expression and its effects on LDH release, antioxidant enzyme activity, apoptotic proteins, and β-III-tubulin expression. RESULTS: BCTS exhibited a pure perovskite phase, densely packed grains, and favorable hydrophilicity. It did not affect BV2 cell viability but inhibited LPS-induced M1 microglial activation, reducing the expression of TNF-α, IL-1β, and IL-6. Simultaneously, BCTS promoted M2 microglial polarization, upregulating IL-4, IL-10, and TGF-β1. In PC12 cells, BCTS-CM increased cell survival, antioxidant activities, Bcl-2, and β-III-tubulin expression, while decreasing LDH release, MDA content, BAX and Cleaved Caspase-3 expression. BCTS-induced neuroprotection is mediated by the suppression of the IL-6/JAK2/STAT3 signaling pathway, as evidenced by the fact that IL-6 supplementation counteracts this protection while AG490 treatment further reinforces it compared to BCTS-CM alone. In the spinal cord injury rat model, BCTS inhibited the expression of microglia and inflammatory factors at the injury site, while improving the BBB score and reducing the error rate in the grid walking test. CONCLUSION: (Ba,Ca)(Ti,Sn)O(3)-based piezoelectric ceramics exhibit neuroprotective effects by inhibiting IL-6 secretion from microglia, thereby preventing the activation of the IL-6/JAK2/STAT3 signaling pathway in neurons.