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-β-galactosidase activity, and examined GABAA 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-β-galactosidase levels, and upregulated GABAA receptors. This study demonstrated that the location of the GABAA receptor is affected by hypoxia or UTI.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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This research was supported by Korea University Ansan Hospital grant.
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Conceptualization: YSK and TJM; Methodology: S-HS and TJM; Formal analysis and investigation: YSK, S-HS, and TJM; Writing—original draft preparation: YSK and S-HS; Writing—review and editing: YSK and TJM; Funding acquisition: TJM; Resources: S-HS and TJM; Supervision: YSK and TJM.
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This study was approved by the Korea University Institutional Animal Care and Use Committee (IACUC number: KOREA-2018-0029).
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Kim, Y.S., Sohn, SH. & Min, T.J. Protective Effect of Ulinastatin on Cognitive Function After Hypoxia. Neuromol Med 25, 136–143 (2023). https://doi.org/10.1007/s12017-022-08721-2
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DOI: https://doi.org/10.1007/s12017-022-08721-2