Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States of America.
Center for Neural Basis of Cognition, Pittsburgh, PA, United States of America.
J Neural Eng. 2023 Sep 1;20(4):046044. doi: 10.1088/1741-2552/aceca5.
. Electrical stimulation has had a profound impact on our current understanding of nervous system physiology and provided viable clinical options for addressing neurological dysfunction within the brain. Unfortunately, the brain's immune suppression of indwelling microelectrodes currently presents a major roadblock in the long-term application of neural recording and stimulating devices. In some ways, brain trauma induced by penetrating microelectrodes produces similar neuropathology as debilitating brain diseases, such as Alzheimer's disease (AD), while also suffering from end-stage neuron loss and tissue degeneration. The goal of the present study was to understand whether there may be any parallel mechanisms at play between brain injury from chronic microelectrode implantation and those of neurodegenerative disorder.. We used two-photon microscopy to visualize the accumulation, if any, of age- and disease-associated factors around chronically implanted electrodes in both young and aged mouse models of AD.. We determined that electrode injury leads to aberrant accumulation of lipofuscin, an age-related pigment, in wild-type and AD mice alike. Furthermore, we reveal that chronic microelectrode implantation reduces the growth of pre-existing Alzheimer's plaques while simultaneously elevating amyloid burden at the electrode-tissue interface. Lastly, we uncover novel spatial and temporal patterns of glial reactivity, axonal and myelin pathology, and neurodegeneration related to neurodegenerative disease around chronically implanted microelectrodes.. This study offers multiple novel perspectives on the possible neurodegenerative mechanisms afflicting chronic brain implants, spurring new potential avenues of neuroscience investigation and design of more targeted therapies for improving neural device biocompatibility and treatment of degenerative brain disease.
电刺激对我们当前对神经系统生理学的理解产生了深远的影响，并为解决大脑中的神经功能障碍提供了可行的临床选择。不幸的是，大脑对留置微电极的免疫抑制目前是长期应用神经记录和刺激设备的主要障碍。在某种程度上，穿透微电极引起的脑创伤产生了与神经退行性疾病（如阿尔茨海默病（AD））相似的神经病理学，同时还遭受晚期神经元丧失和组织退化。本研究的目的是了解慢性微电极植入引起的脑损伤与神经退行性疾病之间是否存在任何平行机制。我们使用双光子显微镜来观察慢性植入电极周围是否有年龄相关和疾病相关因素的积累，在 AD 年轻和老年小鼠模型中均如此。我们确定电极损伤导致脂褐素（一种与年龄相关的色素）异常积累，在野生型和 AD 小鼠中均如此。此外，我们揭示慢性微电极植入会减少预先存在的阿尔茨海默病斑块的生长，同时在电极-组织界面处增加淀粉样蛋白负担。最后，我们发现与慢性植入微电极相关的神经退行性疾病周围的神经胶质反应、轴突和髓鞘病理学以及与神经退行性疾病相关的神经退行性的新的时空模式。这项研究为困扰慢性大脑植入物的可能神经退行性机制提供了多个新的视角，为神经科学研究和更有针对性的治疗方法提供了新的潜在途径，以提高神经设备的生物相容性和治疗退行性脑疾病。
