Galectin-3 modulates microglial activation and neuroinflammation in early brain injury after subarachnoid hemorrhage

Aneurysmal subarachnoid hemorrhage (SAH) is a devastating acute cerebrovascular event with high mortality and permanent disability rates. Higher galectin-3 levels on days 1–3 have been shown to predict the development of delayed cerebral infarction or adverse outcomes after SAH. Recent single-cell analysis of microglial transcriptomic diversity in SAH revealed that galectin could influence the development and course of neuroinflammation after SAH. This study aimed to investigate the role and mechanism of galectin-3 in SAH and to determine whether galectin-3 inhibition prevents early brain injury by reducing microglia polarization using a mouse model of SAH and oxyhemoglobin-treated activation of mouse BV2 cells in vitro. We found that the expression of galectin-3 began to increase 12 h after SAH and continued to increase up to 72 h. Importantly, TD139-inhibited galectin-3 expression reduced the release of inflammatory factors in microglial cells. In the experimental SAH model, TD139 treatment alleviated neuroinflammatory damage after SAH and improved defects in neurological functions. Furthermore, we demonstrated that galectin-3 inhibition affected the activation and M1 polarization of microglial cells after SAH. TD139 treatment inhibited the expression of TLR4, p-NF-κB p65, and NF-κB p65 in microglia activated by oxyhemoglobin as well as eliminated the increased expression and phosphorylation of JAK2 and STAT3. These findings suggest that regulating microglia polarization by galectin-3 after SAH to improve neuroinflammation may be a potential therapeutic target. •The mechanism by which galectin-3 regulates microglia in EBI in SAH is unknown.•TD139 significantly improved the clinical prognosis of mice with SAH.•It also reduced the expressions of IL-1, IL-6, and iNOS in vitro and in vivo.•Galectin-3 may promote EBI in SAH by inducing M1-like polarization of microglia.