Williamson Michael R, Le Stephanie P, Franzen Ronald L, Donlan Nicole A, Rosow Jill L, Nicot-Cartsonis Mathilda S, Cervantes Alexis, Deneen Benjamin, Dunn Andrew K, Jones Theresa A, Drew Michael R
Institute for Neuroscience, University of Texas at Austin, Austin, TX, USA.
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
Nat Commun. 2023 Oct 10;14(1):6341. doi: 10.1038/s41467-023-42138-0.
Stroke enhances proliferation of neural precursor cells within the subventricular zone (SVZ) and induces ectopic migration of newborn cells towards the site of injury. Here, we characterize the identity of cells arising from the SVZ after stroke and uncover a mechanism through which they facilitate neural repair and functional recovery. With genetic lineage tracing, we show that SVZ-derived cells that migrate towards cortical photothrombotic stroke in mice are predominantly undifferentiated precursors. We find that ablation of neural precursor cells or conditional knockout of VEGF impairs neuronal and vascular reparative responses and worsens recovery. Replacement of VEGF is sufficient to induce neural repair and recovery. We also provide evidence that CXCL12 from peri-infarct vasculature signals to CXCR4-expressing cells arising from the SVZ to direct their ectopic migration. These results support a model in which vasculature surrounding the site of injury attracts cells from the SVZ, and these cells subsequently provide trophic support that drives neural repair and recovery.
中风可增强脑室下区（SVZ）内神经前体细胞的增殖，并诱导新生细胞向损伤部位进行异位迁移。在此，我们对中风后源自SVZ的细胞特性进行了表征，并揭示了它们促进神经修复和功能恢复的一种机制。通过基因谱系追踪，我们发现，在小鼠中，向皮质光血栓性中风部位迁移的源自SVZ的细胞主要是未分化的前体细胞。我们发现，神经前体细胞的消融或VEGF的条件性敲除会损害神经元和血管的修复反应，并使恢复情况恶化。补充VEGF足以诱导神经修复和恢复。我们还提供了证据表明，梗死灶周围血管产生的CXCL12向源自SVZ的表达CXCR4的细胞发出信号，以指导其异位迁移。这些结果支持了一种模型，即损伤部位周围的血管吸引来自SVZ的细胞，随后这些细胞提供营养支持，从而推动神经修复和恢复。
