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Neuroprotective effects of vitamin C on hypoxic-ischemic brain injury in neonatal mice

Pediatric Research (2025)Cite this article

Abstract

Background

Hypoxic ischemia (HI) is one of the common causes of neonatal brain injury, leading to neurodevelopmental disorders such as cerebral palsy, epilepsy, and cognitive deficits. In this study, we evaluated neuroprotective effects of vitamin C on the neonatal HI brain injury mouse model.

Methods

Brain damage measurement, sensorimotor function in the neonatal period, learning and memory ability in adulthood were carried out in mice treated with vitamin C daily for 7 consecutive days following HI brain injury at postnatal day 7.

Results

Vitamin C treatment significantly reduced the hippocampus damage area, infarction volume, hippocampal neuron loss, and suppressed the neuroinflammation after HI injury. Additionally, it improved performance on neonatal sensorimotor function tests and learning and memory ability in adulthood.

Conclusions

Vitamin C reduced brain injury and improved functional recovery in the neonatal hypoxic ischemia brain damage (HIBD) model.

Impact

  • Vitamin C treatment significantly reduced neuron loss and suppressed the neuroinflammation after hypoxic-ischemic brain injury.

  • Vitamin C treatment enhanced sensorimotor functions in neonates and improved cognitive abilities in adults after hypoxic-ischemic brain injury.

  • Vitamin C could be an attractive candidate drug in clinical trials of hypoxic-ischemic encephalopathy therapy.

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Fig. 1
Fig. 2: Vitamin C treatment reduced the hippocampus loss and infraction area in HI injury mice.
Fig. 3: Vitamin C treatment reduced the hippocampus neuron loss, neurogenesis and suppressed neuroinflammation in HI injury mice.
Fig. 4: Vitamin C promoted neuronal recovery after HI injury in neonatal period.
Fig. 5: Effects of vitamin C on the motor function, learning and memory ability deficits after HI injury in adulthood.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by the fund for Less Developed Regions of the National Natural Science Foundation of China (No. 82260316) to B.Z.

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Author notes

  1. These authors contributed equally: Kaiyi Liu, Xiaoqing Chen.

Authors and Affiliations

  1. Institute of Pediatrics, Children’s Hospital, Fudan University, Shanghai, China

    Kaiyi Liu, Xiaoqing Chen, Fangbing Chen, Wenjuan Dai, Shiyi Zheng, Bi Ze & Yifeng Lin

  2. Department of Neonatology, International Peace Maternity and Children Hospital of China Welfare Institution, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Xiaoqing Chen

  3. Department of Pediatrics, Tibet Autonomous Region People’s Hospital, Lhasa, China

    Bi Ze

  4. Key Laboratory of Birth Defects, Children’s Hospital, Institutes of Biomedical Sciences, Fudan University, Shanghai, China

    Wenhao Zhou

  5. Division of Neonatology and Center for Newborn Care, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China

    Wenhao Zhou

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Contributions

Kaiyi Liu and Xiaoqing Chen contributed equally to this work. Yifeng Lin and Wenhao Zhou designed the study and supervised the experiments; Kaiyi Liu and Xiaoqing Chen carried out most of the experiments, analyzed results, and wrote the manuscript; Fangbing Chen, Wenjuan Dai, Shiyi Zheng and Bi Ze helped with some experiments. All authors revised the original manuscript and agreed on its contents.

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Correspondence to Wenhao Zhou or Yifeng Lin.

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Liu, K., Chen, X., Chen, F. et al. Neuroprotective effects of vitamin C on hypoxic-ischemic brain injury in neonatal mice. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-03926-0

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