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Cells
Volume 14
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Review

A Comprehensive Review of the Pathophysiology of Neonatal Stroke and a Critique of Current and Future Therapeutic Strategies

by
Victor Mondal
1,
Emily Ross-Munro
1,
Gayathri K. Balasuriya
1,
Ritu Kumari
1,
Md. Munnaf Hossen
1,
Mohammed Ageeli
1,
Kate Firipis
2,3,4,
David R. Nisbet
4,5,6,7,
Glenn F. King
8,9,
Richard J. Williams
10,
Pierre Gressens
11,
Jeanie L. Y. Cheong
12,13,14,
Flora Y. Wong
15,16,17,
David W. Walker
1,17,
Mary Tolcos
1 and
Bobbi Fleiss
1,11,*
1
School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia
2
O’Brien Department, St Vincent’s Institute for Medical Research, Fitzroy, VIC 3065, Australia
3
Department of Medicine, St Vincent’s Hospital, Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Parkville, Melbourne, VIC 3010, Australia
4
Aikenhead Centre for Medical Discovery, St Vincent’s Hospital, Fitzroy, VIC 3065, Australia
5
Department of Biomedical Engineering, Faculty of Engineering and Information Technology, The University of Melbourne, Parkville, VIC 3010, Australia
6
The Graeme Clark Institute, The University of Melbourne, Parkville, VIC 3010, Australia
7
Medical School, Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Parkville, VIC 3010, Australia
8
Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia
9
Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, St Lucia, QLD 4072, Australia
10
School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia
11
Université Paris Cité, Inserm, NeuroDiderot, 75019 Paris, France
12
Clinical Sciences, Murdoch Children’s Research Institute, Parkville, VIC 3052, Australia
13
Neonatal Services, Royal Women’s Hospital, Parkville, VIC 3052, Australia
14
Department of Obstetrics, Gynaecology and Newborn Health, and Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, Australia
15
Monash Newborn, Monash Children’s Hospital, Clayton, VIC 3168, Australia
16
Department of Paediatrics, Monash University, Clayton, VIC 3168, Australia
17
The Ritchie Centre and Hudson Institute, Monash University, Clayton, VIC 3168, Australia
 
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Author to whom correspondence should be addressed.
Cells 2025, 14(12), 910; https://doi.org/10.3390/cells14120910 (registering DOI)
Submission received: 15 May 2025 / Revised: 7 June 2025 / Accepted: 12 June 2025 / Published: 16 June 2025
(This article belongs to the Section Cells of the Nervous System)
Versions Notes

Abstract

Within the first 28 days after birth, more than 1 in every 2500 newborns will suffer a stroke. The weekly-adjusted risk of stroke for a term-born infant is threefold higher than for a male smoker aged 50 to 59 years with hypertension and diabetes. Neonatal stroke has significant clinical and socio-economic consequences, leading to cerebral palsy, epilepsy, and a range of motor, sensory, and cognitive impairments. Currently, there is no treatment for the brain damage caused by neonatal stroke. In this review, we outline the differences in the complex interplay of inflammation, excitotoxicity, oxidative stress, and cell death after stroke between adults and neonates, which limits the direct transfer of knowledge between studies for understanding injury. We comprehensively document what is known about the pathophysiology of neonatal stroke and critically evaluate current therapeutic strategies, emphasising the urgent need for innovative treatments tailored to suit the neonatal brain. This analysis reveals that treatment with an injectable hydrogel scaffold, a three-dimensional, water-swollen polymer network, may be an innovative, viable approach to improve outcomes for infants suffering from the most severe forms of brain injury arising from neonatal stroke.
Keywords: regeneration; perinatal brain injury; biomedical engineering; hydrogel; cerebral palsy regeneration; perinatal brain injury; biomedical engineering; hydrogel; cerebral palsy

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MDPI and ACS Style

Mondal, V.; Ross-Munro, E.; Balasuriya, G.K.; Kumari, R.; Hossen, M.M.; Ageeli, M.; Firipis, K.; Nisbet, D.R.; King, G.F.; Williams, R.J.; et al. A Comprehensive Review of the Pathophysiology of Neonatal Stroke and a Critique of Current and Future Therapeutic Strategies. Cells 2025, 14, 910. https://doi.org/10.3390/cells14120910

AMA Style

Mondal V, Ross-Munro E, Balasuriya GK, Kumari R, Hossen MM, Ageeli M, Firipis K, Nisbet DR, King GF, Williams RJ, et al. A Comprehensive Review of the Pathophysiology of Neonatal Stroke and a Critique of Current and Future Therapeutic Strategies. Cells. 2025; 14(12):910. https://doi.org/10.3390/cells14120910

Chicago/Turabian Style

Mondal, Victor, Emily Ross-Munro, Gayathri K. Balasuriya, Ritu Kumari, Md. Munnaf Hossen, Mohammed Ageeli, Kate Firipis, David R. Nisbet, Glenn F. King, Richard J. Williams, and et al. 2025. "A Comprehensive Review of the Pathophysiology of Neonatal Stroke and a Critique of Current and Future Therapeutic Strategies" Cells 14, no. 12: 910. https://doi.org/10.3390/cells14120910

APA Style

Mondal, V., Ross-Munro, E., Balasuriya, G. K., Kumari, R., Hossen, M. M., Ageeli, M., Firipis, K., Nisbet, D. R., King, G. F., Williams, R. J., Gressens, P., Cheong, J. L. Y., Wong, F. Y., Walker, D. W., Tolcos, M., & Fleiss, B. (2025). A Comprehensive Review of the Pathophysiology of Neonatal Stroke and a Critique of Current and Future Therapeutic Strategies. Cells, 14(12), 910. https://doi.org/10.3390/cells14120910

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