Targeting Macrophage Migration Inhibitory Factor Ameliorates Brain Injury After Intracerebral Hemorrhage in Male Mice

ABSTRACT Macrophage migration inhibitory factor (MIF) has been reported as a detrimental factor in ischemic stroke in male animals. MIF concentration is increased in the cerebrospinal fluid and serum in hemorrhagic stroke patients. However, the roles of MIF in intracerebral hemorrhage (ICH) are still uncertain. This study examined the specific mechanisms of MIF in brain injury following ICH in mice. Firstly, adult male C57BL/6J mice received an intracaudate injection of autologous arterial blood or saline solution. Perihematomal tissues were harvested to measure MIF levels. Secondly, mice received an intracaudate injection of recombinant mouse MIF (rMIF) or saline. Thirdly, mice were treated with ISO‐1 or vehicle after modeling. MRI scans and behavioral tests were conducted in all parts. All mice were euthanized post‐MRI scans, and the harvested brain tissues were utilized for immunochemistry or western blot analysis. We observed that hematolysis occurred at day 1 after ICH initially, and increased from day 3 to day 7 in mice. The level of MIF protein was elevated in the perihematomal tissues at the early stage of ICH. Intracerebral injection of rMIF caused brain edema, microglial activation, and neurological dysfunction in male mice. Furthermore, ISO‐1 treatment mitigated brain edema, neuronal apoptosis, neuroinflammation, and neurological deficits at day 3 post‐ICH in these mice. The level of MIF protein is elevated following ICH and contributes to secondary brain damage following ICH. Targeting MIF could serve as a potential personalized treatment strategy for ICH.