PDF(Pubmed)
Abstract：
Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia, however no effective treatments are available. Here, based on magnetic resonance imaging studies of patients with white matter damage, we found that this damage is associated with disorganized cortical structure. In a mouse model, optogenetic activation of glutamatergic neurons in the somatosensory cortex significantly promoted oligodendrocyte progenitor cell (OPC) proliferation, remyelination in the corpus callosum, and recovery of cognitive ability after cerebral hypoperfusion. The therapeutic effect of such stimulation was restricted to the upper layers of the cortex, but also spanned a wide time window after ischemia. Mechanistically, enhancement of glutamatergic neuron-OPC functional synaptic connections is required to achieve the protection effect of activating cortical glutamatergic neurons. Additionally, skin stroking, an easier method to translate into clinical practice, activated the somatosensory cortex, thereby promoting OPC proliferation, remyelination and cognitive recovery following cerebral hypoperfusion. In summary, we demonstrated that activating glutamatergic neurons in the somatosensory cortex promotes the proliferation of OPCs and remyelination to recover cognitive function after chronic cerebral hypoperfusion. It should be noted that this activation may provide new approaches for treating ischemic vascular dementia via the precise regulation of glutamatergic neuron-OPC circuits.
摘要：
慢性脑低灌注可引起进行性脱髓鞘以及缺血性血管性痴呆,然而，没有有效的治疗方法。这里,基于脑白质损伤患者的磁共振成像研究，我们发现这种损伤与皮质结构紊乱有关.在老鼠模型中，在体感皮层中谷氨酸能神经元的光遗传学激活显着促进少突胶质祖细胞（OPC）的增殖，call体髓鞘再生，脑灌注不足后认知能力的恢复。这种刺激的治疗效果仅限于皮层的上层，但缺血后也跨越了很宽的时间窗。机械上,谷氨酸能神经元-OPC功能性突触连接的增强是实现激活皮质谷氨酸能神经元的保护作用所必需的。此外,皮肤抚摸,一种更容易转化为临床实践的方法，激活了体感皮层，从而促进OPC扩散，脑低灌注后的髓鞘再生和认知恢复。总之,我们证明，在慢性脑低灌注后，激活体感皮层中的谷氨酸能神经元促进OPCs的增殖和髓鞘再生以恢复认知功能。应该注意的是，这种激活可能通过精确调节谷氨酸能神经元-OPC电路为治疗缺血性血管性痴呆提供了新的方法。
