Department of Neurology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California 90095.
Department of Neurology, Weill Institute for Neuroscience, University of California-San Francisco, San Francisco, California 94158.
J Neurosci. 2023 Nov 8;43(45):7489-7500. doi: 10.1523/JNEUROSCI.1425-23.2023.
Stroke is one of the most common causes of disability, and there are few treatments that can improve recovery after stroke. Therapeutic development has been hindered because of a lack of understanding of precisely how neural circuits are affected by stroke, and how these circuits change to mediate recovery. Indeed, some of the hypotheses for how the CNS changes to mediate recovery, including remapping, redundancy, and diaschisis, date to more than a century ago. Recent technological advances have enabled the interrogation of neural circuits with ever greater temporal and spatial resolution. These techniques are increasingly being applied across animal models of stroke and to human stroke survivors, and are shedding light on the molecular, structural, and functional changes that neural circuits undergo after stroke. Here we review these studies and highlight important mechanisms that underlie impairment and recovery after stroke. We begin by summarizing knowledge about changes in neural activity that occur in the peri-infarct cortex, specifically considering evidence for the functional remapping hypothesis of recovery. Next, we describe the importance of neural population dynamics, disruptions in these dynamics after stroke, and how allocation of neurons into spared circuits can restore functionality. On a more global scale, we then discuss how effects on long-range pathways, including interhemispheric interactions and corticospinal tract transmission, contribute to post-stroke impairments. Finally, we look forward and consider how a deeper understanding of neural circuit mechanisms of recovery may lead to novel treatments to reduce disability and improve recovery after stroke.
中风是导致残疾的最常见原因之一，目前几乎没有治疗方法可以改善中风后的恢复情况。由于缺乏对中风如何影响神经回路以及这些回路如何变化以介导恢复的确切理解，治疗方法的开发受到了阻碍。事实上，一些关于中枢神经系统如何变化以介导恢复的假说，包括重新映射、冗余和休眠，可追溯到一个多世纪以前。最近的技术进步使我们能够以更高的时间和空间分辨率来检测神经回路。这些技术越来越多地应用于中风动物模型和中风幸存者，并揭示了中风后神经回路经历的分子、结构和功能变化。在这里，我们回顾这些研究，并强调中风后损伤和恢复的重要机制。我们首先总结了中风后梗死周围皮层中神经活动变化的知识，特别是考虑了恢复的功能重映射假说的证据。接下来，我们描述了神经元群体动力学的重要性、中风后这些动力学的破坏，以及神经元如何分配到保留的回路中以恢复功能。在更广泛的范围内，我们讨论了长程通路（包括大脑半球间的相互作用和皮质脊髓束的传递）的影响如何导致中风后的损伤。最后，我们展望未来，考虑对神经回路恢复机制的更深入理解如何为减少中风后的残疾和改善恢复提供新的治疗方法。
