Faculty of Medicine and Health Sciences, Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Department of Radiology and Nuclear Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
Eur J Neurosci. 2018 Jun;47(12):1414-1428. doi: 10.1111/ejn.13959. Epub 2018 Jun 8.
Neuroplasticity after ischaemic injury involves both spontaneous rewiring of neural networks and circuits as well as functional responses in neurogenic niches. These events involve complex interactions with activated microglia, which evolve in a dynamic manner over time. Although the exact mechanisms underlying these interactions remain poorly understood, increasing experimental evidence suggests a determining role of pro- and anti-inflammatory microglial activation profiles in shaping both synaptogenesis and neurogenesis. While the inflammatory response of microglia was thought to be detrimental, a more complex profile of the role of microglia in tissue remodelling is emerging. Experimental evidence suggests that microglia in response to injury can rapidly modify neuronal activity and modulate synaptic function, as well as be beneficial for the proliferation and integration of neural progenitor cells (NPCs) from endogenous neurogenic niches into functional networks thereby supporting stroke recovery. The manner in which microglia contribute towards sculpting neural synapses and networks, both in terms of activity-dependent and homeostatic plasticity, suggests that microglia-mediated pro- and/or anti-inflammatory activity may significantly contribute towards spontaneous neuronal plasticity after ischaemic lesions. In this review, we first introduce some of the key cellular and molecular mechanisms underlying neuroplasticity in stroke and then proceed to discuss the crosstalk between microglia and endogenous neuroplasticity in response to brain ischaemia with special focus on the engagement of synapses and neural networks and their implications for grey matter integrity and function in stroke repair.
缺血性损伤后的神经可塑性既涉及神经网络和回路的自发重新布线，也涉及神经发生龛中的功能反应。这些事件涉及与激活的小胶质细胞的复杂相互作用，小胶质细胞随时间呈动态变化。尽管这些相互作用的确切机制仍知之甚少，但越来越多的实验证据表明，促炎和抗炎小胶质细胞激活谱在塑造突触发生和神经发生方面起着决定性作用。虽然小胶质细胞的炎症反应被认为是有害的，但小胶质细胞在组织重塑中的作用呈现出更为复杂的特征。实验证据表明，小胶质细胞在受伤后可以迅速改变神经元活动并调节突触功能，并且对来自内源性神经发生龛的神经祖细胞 (NPC) 的增殖和整合到功能网络中有益，从而支持中风后的恢复。小胶质细胞在塑造神经突触和网络方面的方式，无论是在活动依赖性还是在稳态可塑性方面，都表明小胶质细胞介导的促炎和/或抗炎活性可能对缺血性损伤后的自发神经元可塑性有重大贡献。在这篇综述中，我们首先介绍了中风后神经可塑性的一些关键细胞和分子机制，然后讨论了小胶质细胞与内源性神经可塑性之间的相互作用，以响应脑缺血，特别关注突触和神经网络的参与及其对中风修复中灰质完整性和功能的影响。
