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Article

Neuroserpin: A Potential Neuroprotective Agent in Mild Neonatal Hypoxic–Ischaemic Encephalopathy

1
Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Sherrington Rd, Oxford OX1 3PT, UK
2
Laboratory of Pathological Biochemistry, Kyoto Pharmaceutical University, Misasagi Nakauchi-cho, Yamashina-ku, Kyoto 607-8414, Japan
3
Department of Neurology, University of California, San Francisco, Sandler Neuroscience Building, 675 Nelson Rising Lane, San Francisco, CA 94158, USA
4
JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, China
*
Authors to whom correspondence should be addressed.
Cells 2025, 14(23), 1840; https://doi.org/10.3390/cells14231840
Submission received: 20 October 2025 / Revised: 13 November 2025 / Accepted: 18 November 2025 / Published: 21 November 2025
(This article belongs to the Special Issue Perinatal Brain Injury—from Pathophysiology to Therapy)

Abstract

Neonatal hypoxic–ischaemic encephalopathy (HIE) remains a leading cause of infant morbidity and mortality worldwide, with therapeutic hypothermia being the only clinically approved treatment. This study investigates the cortical expression pattern of neuroserpin during postnatal brain development and evaluates its neuroprotective potential in hypoxia–ischaemia (HI)-induced brain damage using a modified Rice–Vannucci model. Experiments were conducted in both male and female neuroserpin knockout (KO) mice and through administration of exogenous neuroserpin into the brain. Between postnatal day 4 to 14 (P4–P14), neuroserpin-immunoreactive cell density peaked at P8–P10 in cortical layers 5 and 6b, with a gradual increase in layers 2/3 and minimal changes in layers 4 and 6a. Despite comparable levels of ischaemic brain damage between the KO and wild-type (WT) mice, exogenous neuroserpin administration suppressed the HI-induced oxidative stress. Additionally, it reduced microglial activation and reactive astrogliosis in the cortex in mild HIE, mitigating cortical thinning and preserving neuronal distribution. These findings suggest that endogenous neuroserpin alone is insufficient for neuroprotection against HI-induced damage, but exogenous neuroserpin shows promise as a pharmacological intervention for mild neonatal HIE.
Keywords: neonatal hypoxic–ischaemic encephalopathy; Rice–Vannucci model; neuroserpin; neuroprotection neonatal hypoxic–ischaemic encephalopathy; Rice–Vannucci model; neuroserpin; neuroprotection

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MDPI and ACS Style

Kawashita, E.; Fukuzaki, Y.; Fischer, J.; Shi, L.; Liao, Y.; Millar, L.J.; Zhong, P.; Hoerder-Suabedissen, A.; Soares, L.C.; Molnár, Z. Neuroserpin: A Potential Neuroprotective Agent in Mild Neonatal Hypoxic–Ischaemic Encephalopathy. Cells 2025, 14, 1840. https://doi.org/10.3390/cells14231840

AMA Style

Kawashita E, Fukuzaki Y, Fischer J, Shi L, Liao Y, Millar LJ, Zhong P, Hoerder-Suabedissen A, Soares LC, Molnár Z. Neuroserpin: A Potential Neuroprotective Agent in Mild Neonatal Hypoxic–Ischaemic Encephalopathy. Cells. 2025; 14(23):1840. https://doi.org/10.3390/cells14231840

Chicago/Turabian Style

Kawashita, Eri, Yumi Fukuzaki, Jan Fischer, Lei Shi, Yumei Liao, Lancelot Jamie Millar, Peiyun Zhong, Anna Hoerder-Suabedissen, Luana Campos Soares, and Zoltán Molnár. 2025. "Neuroserpin: A Potential Neuroprotective Agent in Mild Neonatal Hypoxic–Ischaemic Encephalopathy" Cells 14, no. 23: 1840. https://doi.org/10.3390/cells14231840

APA Style

Kawashita, E., Fukuzaki, Y., Fischer, J., Shi, L., Liao, Y., Millar, L. J., Zhong, P., Hoerder-Suabedissen, A., Soares, L. C., & Molnár, Z. (2025). Neuroserpin: A Potential Neuroprotective Agent in Mild Neonatal Hypoxic–Ischaemic Encephalopathy. Cells, 14(23), 1840. https://doi.org/10.3390/cells14231840

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