Cheng Michelle Y, Aswendt Markus, Steinberg Gary K
Department of Neurosurgery, R281, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305-5327, USA.
Neurotherapeutics. 2016 Apr;13(2):325-40. doi: 10.1007/s13311-015-0411-5.
Stroke is a leading cause of death and disability in the USA, yet treatment options are very limited. Functional recovery can occur after stroke and is attributed, in part, to rewiring of neural connections in areas adjacent to or remotely connected to the infarct. A better understanding of neural circuit rewiring is thus an important step toward developing future therapeutic strategies for stroke recovery. Because stroke disrupts functional connections in peri-infarct and remotely connected regions, it is important to investigate brain-wide network dynamics during post-stroke recovery. Optogenetics is a revolutionary neuroscience tool that uses bioengineered light-sensitive proteins to selectively activate or inhibit specific cell types and neural circuits within milliseconds, allowing greater specificity and temporal precision for dissecting neural circuit mechanisms in diseases. In this review, we discuss the current view of post-stroke remapping and recovery, including recent studies that use optogenetics to investigate neural circuit remapping after stroke, as well as optogenetic stimulation to enhance stroke recovery. Multimodal approaches employing optogenetics in conjunction with other readouts (e.g., in vivo neuroimaging techniques, behavior assays, and next-generation sequencing) will advance our understanding of neural circuit reorganization during post-stroke recovery, as well as provide important insights into which brain circuits to target when designing brain stimulation strategies for future clinical studies.
中风是美国死亡和残疾的主要原因之一，但治疗选择非常有限。中风后功能恢复是可能的，部分原因是梗死灶附近或远距离连接区域的神经连接重新布线。因此，更好地理解神经回路重新布线是开发未来中风恢复治疗策略的重要一步。由于中风会破坏梗死灶周围和远距离连接区域的功能连接，因此研究中风后恢复过程中的全脑网络动态非常重要。光遗传学是一种革命性的神经科学工具，它利用生物工程改造的光敏蛋白在毫秒级时间内选择性激活或抑制特定细胞类型和神经回路，从而在剖析疾病神经回路机制方面具有更高的特异性和时间精度。在这篇综述中，我们讨论了目前对中风后重新映射和恢复的看法，包括最近使用光遗传学研究中风后神经回路重新映射以及光遗传学刺激增强中风恢复的研究。将光遗传学与其他读数（如体内神经成像技术、行为分析和下一代测序）相结合的多模态方法，将增进我们对中风后恢复过程中神经回路重组的理解，并为未来临床研究设计脑刺激策略时确定靶向哪些脑回路提供重要见解。
