Advanced age is not a barrier to chronic intracortical single-unit recording in rat cortex

Nicholas F. Nolta, Michael B. Christensen, Patrick A. Tresco
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Abstract

Available evidence suggests that as we age, our brain and immune system undergo changes that increase our susceptibility to injury, inflammation, and neurodegeneration. Since a significant portion of the potential patients treated with a microelectrode-based implant may be older, it is important to understand the recording performance of such devices in an aged population.We studied the chronic recording performance and the foreign body response (FBR) to a clinically used microelectrode array implanted in the cortex of 18-month-old Sprague Dawley rats.To the best of our knowledge, this is the first preclinical study of its type in the older mammalian brain. Here, we show that single-unit recording performance was initially robust then gradually declined over a 12-week period, similar to what has been previously reported using younger adult rats and in clinical trials. In addition, we show that FBR biomarker distribution was similar to what has been previously described for younger adult rats implanted with multi-shank recording arrays in the motor cortex. Using a quantitative immunohistochemcal approach, we observed that the extent of astrogliosis and tissue loss near the recording zone was inversely related to recording performance. A comparison of recording performance with a younger cohort supports the notion that aging, in and of itself, is not a limiting factor for the clinical use of penetrating microelectrode recording arrays for the treatment of certain CNS disorders.
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高龄并不妨碍大鼠皮层内单个单元的长期记录
现有证据表明,随着年龄的增长,大脑和免疫系统会发生变化,使我们更容易受到损伤、炎症和神经变性的影响。我们研究了植入 18 个月大 Sprague Dawley 大鼠大脑皮层的临床常用微电极阵列的慢性记录性能和异物反应(FBR)。据我们所知,这是首次在老年哺乳动物大脑中进行此类临床前研究。据我们所知,这是首次在年龄较大的哺乳动物大脑中进行此类临床前研究。在这里,我们发现单个单元的记录性能最初很稳定,然后在 12 周内逐渐下降,这与之前使用年龄较小的成年大鼠和临床试验中的报道相似。此外,我们还发现,FBR 生物标记物的分布与之前在运动皮层植入多柄记录阵列的年轻成年大鼠身上所描述的情况相似。通过定量免疫组化方法,我们观察到记录区附近星形胶质细胞增多和组织缺失的程度与记录效果成反比。与年轻组群的记录效果比较支持这样一种观点,即衰老本身并不是穿透性微电极记录阵列用于临床治疗某些中枢神经系统疾病的限制因素。
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