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Protective Effect of Ulinastatin on Cognitive Function After Hypoxia

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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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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This research was supported by Korea University Ansan Hospital grant.

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Authors and Affiliations

  1. Department of Anesthesiology and Pain Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea

    Young Sung Kim

  2. Department of Anesthesiology and Pain Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, South Korea

    Sung-Hwa Sohn & Too Jae Min

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  1. Young Sung Kim
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  2. Sung-Hwa Sohn
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  3. Too Jae Min
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Contributions

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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Correspondence to Too Jae Min.

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The authors declare that they have no conflict of interest.

Ethical Approval

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

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