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 (2): 695-703.doi: 10.4103/NRR.NRR-D-23-02092

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

水凝胶包埋的电刺激脑室下区干细胞移植到脑卒中梗死腔可促进小鼠功能恢复

  

  • 出版日期:2026-02-15 发布日期:2025-05-24

Grafts of hydrogel-embedded electrically stimulated subventricular stem cells into the stroke cavity improves functional recovery of mice

Andreea-Mihaela Cercel1, 2, #, Ianis KS Boboc3, 4, #, Roxana Surugiu1, 5, #, Thorsten R. Doeppner4, 6, Dirk M. Hermann5 , Bogdan Catalin3, 4, Andrei Gresita7, *, Aurel Popa-Wagner1, 5, *   

  1. 1 Experimental Research Center for Normal and Pathological Aging, University of Medicine and Pharmacy Craiova, Craiova, Romania;  2 Doctoral School, University of Medicine and Pharmacy Craiova, Craiova, Romania;  3 Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, Craiova, Romania;  4 Department of Neurology, University Medical Center Göttingen, Göttingen, Germany;  5 Chair of Vascular Neurology and Dementia, Department of Neurology, University Hospital Essen, Essen, Germany;  6 Department of Neurology, University of Giessen Medical School, Giessen, Germany;  7 Department of Biomedical Sciences, New York Institute of Technology, College of Osteopathic Medicine, Old Westbury, NY, USA
  • Online:2026-02-15 Published:2025-05-24
  • Contact: Andrei Gresita, PhD, MD, agresita@nyit.edu; Aurel Popa-Wagner, PhD, MD, aurel.popa-wagner@geriatrics-healthyageing.com.
  • Supported by:
    This work was supported by European Union Funding Programme, PNRR, No. 760058 (to DMH) and the UEFISCDI Project, No. PN-III-P4-IDPCE-2020-059 (to APW).

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摘要：

脑卒中治疗的主要目的是促进大脑修复，改善脑缺血后的行为。干细胞疗法的主要障碍之一是脑缺血引起的强烈炎症反应，与之相关的脑巨噬细胞吞噬活动会清除治疗细胞和/或基于细胞的药物载体。为了解决这些问题，先在脑室下区电刺激神经发生，然后分离增殖细胞，包括新形成的神经元，随后将其与营养水凝胶混合。然后将这种混合物转移到脑卒中后第 14 天小鼠的脑卒中梗死腔中。结果发现，经过治疗的小鼠行为表现有所改善。免疫染色显示，干细胞标记物nestin、神经上皮的标志Mash1和未成熟神经元标记物双皮质素阳性细胞在移植区域存活了2周，这可能是由于吞噬活性降低和支持性血管生成所致。这些结果表明，将有活力的SVZ干细胞与保护性营养凝胶结合，直接移植到梗死腔，是改善脑缺血后神经功能恢复的可行方法。

https://orcid.org/0000-0003-4574-8605 (Aurel Popa-Wagner)

关键词: 电刺激, 脑卒中模型, 脑室下区, 神经干细胞, 水凝胶, 行为恢复, 双皮质素, Mash1, 巢蛋白

Abstract: The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia. One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly formed neurons to the damaged area. However, only a small percentage of these neurons survive, and many do not reach the damaged area, possibly because the corpus callosum impedes the migration of subventricular zone-derived stem cells into the lesioned cortex. A second major obstacle to stem cell therapy is the strong inflammatory reaction induced by cerebral ischemia, whereby the associated phagocytic activity of brain macrophages removes both therapeutic cells and/or cell-based drug carriers. To address these issues, neurogenesis was electrically stimulated in the subventricular zone, followed by isolation of proliferating cells, including newly formed neurons, which were subsequently mixed with a nutritional hydrogel. This mixture was then transferred to the stroke cavity of day 14 post-stroke mice. We found that the performance of the treated animals improved in behavioral tests, including novel object, open field, hole board, grooming, and “time-to-feel” adhesive tape tests. Furthermore, immunostaining revealed that the stem cell marker nestin, the neuroepithelial marker Mash1, and the immature neuronal marker doublecortin-positive cells survived in the transplanted area for 2 weeks, possibly due to reduced phagocytic activity and supportive angiogenesis. These results clearly indicate that the transplantation of committed subventricular zone stem cells combined with a protective nutritional gel directly into the infarct cavity after the peak of stroke-induced neuroinflammation represents a feasible approach to improve neurorestoration after cerebral ischemia.

Key words: ANXA3, behavioral recovery, doublecortin, electrical stimulation, Mash1, nestin, stroke, subventricular neural stem cells, supportive hydrogel, vascular cell adhesion molecule 1