清除和再殖小胶质细胞对皮层内植入电极诱导炎症的调控机制

Chronic electrode implant is an important brain-computer interface technology used to read or write neural signals. However, implanted electrodes in the cortex typically fail within weeks or months. The failure greatly limits their applications, and becomes a key challenge. The past research mainly focused on the improvements of electrode and electrode materials. However, recent studies on chronic inflammation in the central nervous system suggest that inflammation regulated by microglia cells is the key to the failure. we propose that microglia is the target to solve the problem. Our publlished results showed that CSF1R inhibitor PLX5622 could be used to deplete microglia (about 99%). After withdrawal of the drug, microglia cells can rapidly repopulate and replace the original microglial cells. Repopulated microglia originates from self-proliferation. This study planned to establish a mouse model for chronic electrode implantation in the cortex, which is used to study the inhibitory effect of PLX5622 on the inflammation induced by the implanted electrode. Mechanisms of microglia in chronic inflammation and the protective effects on cells around electrodes will be elucidated through the microglial replacement. It is promising to elucidate the regulatory mechanisms of microglia in this inflammatory model and to develop a new way for solving the implant failure.

慢性植入电极是一种重要的脑机接口技术，用于读取或写入神经信号。然而，这种电极在皮层内植入后会在数周到数月内因记录不到信号而失效，极大限制了其应用，这成了该技术面临的重要挑战。过去的研究主要聚焦于电极和电极材料的改进。而中枢神经系统慢性炎症的研究提示，小胶质细胞调控的炎症才是导致电极失效的关键，本研究提出以小胶质细胞为靶点来解决电极失效的问题。我们既往的成果显示，使用CSF1R抑制剂PLX5622可以清除约99%的小胶质细胞，停药后，小胶质细胞能快速再殖替换原有细胞，这些细胞源于自我增殖。本研究拟以建立皮层内慢性植入电极的小鼠模型，通过使用PLX5622清除小胶质细胞，探索其对植入电极诱发炎症的抑制作用。通过小胶质细胞的再殖替换，阐明再殖小胶质细胞对慢性炎症的作用机制，以及对电极周围细胞的保护作用。本研究有望阐明小胶质细胞在该模型中的炎症调控机制，并为解决电极植入失效的问题拓展出新思路。

本研究提出以小胶质细胞为靶点来解决侵入式脑机接口中植入电极因细胞免疫排斥导致失效的问题。本研究拟通过使用CSF1R抑制剂PLX5622清除小胶质细胞，探索其对植入电极诱发炎症的抑制作用；通过小胶质细胞的再殖替换，阐明再殖小胶质细胞对慢性炎症的作用机制，以及对电极周围细胞的保护作用。项目负责人团队基于小胶质细胞清除技术，开发了三种用外源性细胞替换原生小胶质细胞的方案，实现在全CNS范围内高效地细胞替换，为神经退行性病变的治疗提供了全新的思路和实现方案；同时制作了基于纳米锥阵列的铂-氧化铱神经微电极，并发现该电极显著增强了小胶质细胞与基底的粘附力，表现出优异的生物相容性，有望广泛用于各种可植入/可穿戴设备、生物传感、能量存储和其他实际应用。