Blocking of Tim-3 Ameliorates Spinal Cord Ischemia-Reperfusion Injury Through Inhibiting Neuroinflammation and Promoting M1-to-M2 Phenotypic Polarization of Microglia.

Background: Blocking of Tim-3 exerts therapeutic effects in a series of ischemia-reperfusion injury (IRI).

Methods: In this work, a cross-clamped aortic arch was conducted to establish SCIRI rat model. Besides, rat spinal microglia was subjected to OGD/R to mimic I/R-like conditions in vitro. The in vivo and in vitro therapeutic effects of Tim-3 antibody in SCIRI were investigated from these aspects: neuronal apoptosis, neuroinflammation, microglia activation, and polarization.

Results: It was verified that Tim-3 was highly expressed in spinal cord tissues of SCIRI rats and blocking of Tim-3 attenuated SCIRI-induced pathological injury, neuronal apoptosis, neuroinflammation, and microglia activation (M1 polarization). In addition, it was verified that Tim-3 was highly expressed in OGD/R-treated rat spinal microglia and blocking of Tim-3 attenuated OGD/R-induced inflammation and spinal microglia activation (M1 polarization).

Conclusions: Tim-3 antibody can exert therapeutic effects in SCIRI through inhibiting neuroinflammation and promoting microglia polarization from M1 to M2 phenotype.