中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (9): 4342-4351.doi: 10.4103/NRR.NRR-D-25-00696

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

代谢性糖工程化神经干细胞促进心脏骤停后脑功能恢复：经鼻腔与脑室内给药比较

  

  • 出版日期:2026-09-15 发布日期:2026-05-21

Intranasal and intracerebroventricular delivery of metabolically glycoengineered neural stem cells to enhance post–cardiac arrest brain recovery

Xiao Liu1, Zhulin Wang1, Jian Du1, Songah Chae1, Subash Marasini1, Madelynn McElroy1, Kevin J. Yarema2, 3, Xiaofeng Jia1, 2, 4, 5, *   

  1. 1Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA; 
    2Department of Biomedical Engineering, The Johns Hopkins School of Medicine, Baltimore, MD, USA; 
    3Translational Cell and Tissue Engineering Center, The Johns Hopkins School of Medicine, Baltimore, MD, USA; 
    4Department of Orthopedics, University of Maryland School of Medicine, Baltimore, MD, USA; 
    5Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
  • Online:2026-09-15 Published:2026-05-21
  • Contact: Xiaofeng Jia, MD, MS, PhD, FCCM, xjia@som.umaryland.edu.
  • Supported by:
    This work was partially supported by R01NS125232 and R01NS110387 from the National Institute of Neurological Disorders and Stroke, USA and 2024-MSCRFD-6401 from Maryland Stem Cell Research Fund (all to XJ).

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摘要：

心脏骤停引发全脑缺血，导致严重神经功能缺损，目前尚无有效治疗手段。神经干细胞移植展现出治疗潜力，但如何实现最佳且稳定的递送效果，同时最大化移植后细胞功能仍面临挑战。代谢性糖工程作为新兴技术，通过修饰神经干细胞糖链结构，有望提升其存活率与治疗效果。实验比较了采用代谢性糖工程化神经干细胞治疗心搏骤停后缺血性脑损伤时，不同给药途径的效果。大鼠分别接受9分钟窒息性心搏骤停（4周）以模拟严重脑损伤和11分钟窒息性心搏骤停（3天）以模拟极重度脑损伤。复苏后3h经鼻腔或脑室内（ICV）给药代谢性糖工程化神经干细胞。复苏后定期评估神经功能缺损及神经行为测试。采用Fluro-Jade C 染色和甲酚紫染色检测神经元损伤。通过免疫荧光染色追踪移植的代谢性糖工程化神经干细胞。恢复早期阶段，与鼻腔给药相比，脑室内给药组在复苏后短期内表现出更优的神经功能缺损评分。复苏后第3天，代谢性糖工程化神经干细胞主要定位于皮层和海马区，其中脑室内给药组的定位比例更高。然而至第4周时，经鼻腔给药组大鼠的运动功能显著优于脑室内给药组，且焦虑/抑郁相关行为减少。该组还表现出更高的代谢性糖工程化神经干细胞存活率，细胞向小脑及脑干的分布更广泛，同时伴随小胶质细胞募集减少。两种给药途径均能促进代谢性糖工程化神经干细胞增强血管新生、神经元分化及突触可塑性。总体而言，鼻腔给药在长期恢复方面与脑室内给药效果相当或更优，而脑室内给药则具有短期优势。这些结果凸显了代谢性糖工程化神经干细胞疗法在促进心搏骤停后恢复方面的潜力，支持根据特定恢复阶段目标制定个性化治疗策略。


https://orcid.org/0000-0003-1445-8525 (Xiaofeng Jia)

关键词: 心搏骤停, 脑室内给药, 鼻腔给药, 缺血性脑损伤, 代谢糖工程, 神经干细胞, 神经再生, 干细胞治疗

Abstract: Cardiac arrest leads to global cerebral ischemia, causing significant neurological deficits with few effective treatments currently available. Neural stem cell (NSC) transplantation has shown therapeutic promise; however, challenges remain to achieve optimal and consistent delivery while maximizing cell functionality post-transplantation. Metabolic glycoengineering (MGE) has emerged as a novel technique to improve NSC viability and therapeutic efficacy by modifying their glycans. This report compares the effects of different delivery routes for this innovative approach of using MGE-modified NSCs (MGE-NSCs) to treat ischemic brain injury post–cardiac arrest. A total of 16 rats were subjected to 9-minute asphyxia cardiac arrest (4 weeks) and 21 rats subjected to 11-minute asphyxia cardiac arrest (3 days) to model severe and very severe brain injury, respectively. The MGE-NSCs were administered either intranasally or intracerebroventricularly (ICV) 3 hours after resuscitation. Neurological deficits and neurobehavior tests were assessed periodically after resuscitation. Neuronal damage was examined with Fluro-Jade C staining and cresyl violet staining. The transplanted MGE-NSCs were tracked using immunofluorescence staining. In the early phase of recovery, the ICV administration resulted in better neurological deficit scores shortly after resuscitation compared with the intranasal route. Three days post-resuscitation, MGE-NSCs were primarily located in the cortex and hippocampus, with a higher percentage in the ICV-treated group. However, by 4 weeks, rats treated with intranasal MGE-NSCs exhibited superior locomotor function and reduced anxiety-/depression-related behaviors compared with those receiving ICV-NSC therapy. This was accompanied by greater survival and distribution of MGE-NSCs to the cerebellum and brainstem, along with reduced microglia recruitment. MGE-NSCs administered via both delivery methods enhanced vascular angiogenesis, neuron differentiation, and synaptic plasticity. Overall, intranasal delivery was as effective or potentially superior to ICV for long-term recovery, whereas ICV conferred short-term advantages. These results highlight the potential of MGE-NSC therapy to enhance post–cardiac arrest recovery, advocating for tailored treatment strategies based on specific recovery phase goals.

Key words: cardiac arrest, intracerebroventricular, intranasal delivery, ischemic brain injury, metabolic glycoengineering, neural stem cell, neuroregeneration, stem cell therapy