Background: Cerebral ischemia-reperfusion injury is an extremely complicated pathological process
that is clinically characterized by high rates of disability and mortality. It is imperative to explore some effective
neuroprotective agents for its treatment. Ulinastatin is a protease inhibitor with anti-inflammatory and antioxidant
activity. For the past few years, new studies of ulinastatin for the treatment of ischemic brain injury have
Objective: We conducted a review to summarize the mechanisms of ulinastatin and analyze its neuroprotective
action against cerebral ischemia–reperfusion injury.
Methods: We reviewed and summarized pertinent reports published between 1993 and 2019 from PubMed, Web
of Science, and Embaseby searching for the scientific terms ulinastatin, cerebral ischemia–reperfusion injury,
neuroprotective, stroke, cardiac arrest, and brain edema.
Results: The protective mechanisms of ulinastatin in the key steps of cerebral ischemia–reperfusion injury include
inhibition of inflammatory response, oxidative stress, neuronal apoptosis, neuronal autophagy, and aquaporin-
4 expression as well as improvement in blood–brain barrier permeability. In addition, we provide a perspective
on potential research directions and clinical safety.
Conclusion: Ulinastatin seems to have the potential to alleviate cerebral ischemia–reperfusion injury. These
findings may be valuable to further promote the research and development of drug candidates and provide novel
and reliable references for rational drug use.