Ulinastatin alleviates early brain injury after intracerebral hemorrhage by inhibiting oxidative stress and neuroinflammation via ROS/MAPK/Nrf2 signaling pathway.

Purpose: Spontaneous intracerebral hemorrhage (ICH) is still a major public health problem, with high mortality and disability. Ulinastatin (UTI) was purified from human urine and has been reported to be anti-inflammatory, organ protective, and antioxidative stress. However, the neuroprotection of UTI in ICH has not been confirmed, and the potential mechanism is unclear. In the present study, we aimed to investigate the neuroprotection and potential molecular mechanisms of UTI in ICH-induced early brain injury in a C57BL/6 mouse model.

Methods: The neurological score, brain water content, neuroinflammatory cytokine levels, oxidative stress levels, and neuronal damage were evaluated.

Results: UTI treatment markedly increased the neurological score, alleviated brain edema, decreased the levels of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and NF-κB, decreased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and upregulated the levels of glutathione (GSH), superoxide dismutase (SOD), and Nrf2. This finding indicated that UTI-mediated inhibition of neuroinflammation and oxidative stress alleviated neuronal damage after ICH. The neuroprotective capacity of UTI is partly dependent on the ROS/MAPK/Nrf2 signaling pathway.

Conclusions: UTI improves neurological outcomes in mice and reduces neuronal death by protecting against neural neuroinflammation and oxidative stress.