Cercel Andreea-Mihaela, Boboc Ianis Ks, Surugiu Roxana, Doeppner Thorsten R, Hermann Dirk M, Catalin Bogdan, Gresita Andrei, Popa-Wagner Aurel
Experimental Research Center for Normal and Pathological Aging, University of Medicine and Pharmacy Craiova, Craiova, Romania.
Doctoral School, University of Medicine and Pharmacy Craiova, Craiova, Romania.
Neural Regen Res. 2026 Feb 1;21(2):695-703. doi: 10.4103/NRR.NRR-D-23-02092. Epub 2024 Nov 13.
JOURNAL/nrgr/04.03/01300535-202602000-00039/figure1/v/2025-05-05T160104Z/r/image-tiff 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.
《期刊》/nrgr/04.03/01300535 - 202602000 - 00039/图1/v/2025 - 05 - 05T160104Z/图像 - tiff 中风治疗的主要目标是刺激脑修复并改善脑缺血后的行为恢复。一种选择是刺激脑室下区的内源性神经发生,并将新形成的神经元引导至受损区域。然而,这些神经元中只有一小部分存活下来,而且许多未能到达受损区域,这可能是因为胼胝体阻碍了脑室下区来源的干细胞迁移到受损皮层。干细胞治疗的第二个主要障碍是脑缺血诱导的强烈炎症反应,由此脑巨噬细胞的相关吞噬活性会清除治疗性细胞和/或基于细胞的药物载体。为了解决这些问题,在脑室下区进行电刺激神经发生,随后分离增殖细胞,包括新形成的神经元,然后将其与营养水凝胶混合。然后将这种混合物转移到中风后14天小鼠的中风腔中。我们发现,在包括新物体、旷场、洞板、梳理和“感受时间粘性胶带”测试等行为测试中,接受治疗的动物表现有所改善。此外,免疫染色显示干细胞标志物巢蛋白、神经上皮标志物Mash1和未成熟神经元标志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。这些结果清楚地表明,在中风诱导的神经炎症高峰期后,将定向分化的脑室下区干细胞与保护性营养凝胶直接移植到梗死腔中是一种改善脑缺血后神经修复的可行方法。