Protective Effect of Ulinastatin on Cognitive Function After Hypoxia

Abstract

Ulinastatin (UTI) has neuroprotective properties. Neurologic insults, including hypoxia and use of anesthetic agents, cause postoperative cognitive dysfunction and alter gamma-aminobutyric acid (GABA) function. This study aimed to assess whether UTI could preserve learning and memory using a zebrafish hypoxic behavior model and biomarkers. Zebrafish (6-8 months of age and 2.5-3.5 cm long) were divided into eight groups as follows: phosphate-buffered saline (PBS) control, hypoxia + PBS, UTI (10,000, 50,000, and 100,000 units/kg), and hypoxia with UTI (10,000, 50,000, and 100,000 units/kg) groups. The endpoints of the T-maze experiment included total time, distance moved, and frequency in target or opposite compartment. We also measured the degree of brain infarction using 2,3,5-triphenyltetrazolium chloride staining, assessed SA-beta-galactosidase activity, and examined GABA(A) receptor expression using real-time polymerase chain reaction. In a dose-dependent manner, UTI affected learning and memory in zebrafish. Despite hypoxia, 100,000 units/kg of UTI preserved preference (time and distance) for the target compartment. More than 50,000 units/kg of UTI also showed reduced hypoxia-induced brain infarction, decreased SA-beta-galactosidase levels, and upregulated GABA(A) receptors. This study demonstrated that the location of the GABA(A) receptor is affected by hypoxia or UTI.