Blood brain barrier (BBB)-disruption in intracortical silicon microelectrode implants.
Blood brain barrier (BBB)-disruption in intracortical silicon microelectrode implants.
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DOI：
10.1016/j.biomaterials.2018.02.036
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发表时间：
2018-05
期刊：
影响因子：
14
通讯作者：
Prasad A
中科院分区：
文献类型：
--
作者：
Bennett C;Samikkannu M;Mohammed F;Dietrich WD;Rajguru SM;Prasad A
在神经组织中长期植入微电极引起的炎症反应是随时间变化的，并已被证明取决于多种因素。在这些因素中，血脑屏障（BBB）破坏已被假设为导致电极失效的主要因素之一。在电极植入期间发生包括BBB和细胞膜破坏的一系列事件，其触发负责小胶质细胞和星形胶质细胞活化、出血、水肿和导致神经元变性和功能障碍的促炎性神经毒性细胞因子释放的多个生化级联反应。通常，将微丝阵列和硅探针缓慢插入神经组织中，而使用气动插入器以高速插入硅犹他州MEA（UMEA）。在这项工作中，我们报告了植入脑组织中的UMEA在不同急性时间点的电极植入物诱导的皮质损伤后遗症，方法是量化介导炎症反应的关键基因以及形成BBB并对BBB功能至关重要的紧密连接（TJ）和粘附连接（AJ）蛋白的表达谱。我们的研究结果表明，相对于所有时间点的幼稚对照，大多数促炎基因都上调。形成TJ和AJ的基因的表达水平下调，提示BBB功能障碍。此外，穿刺组和植入组之间没有显著差异，表明UMEA插入相关创伤对脑组织的影响。我们的研究结果提供了一个深入了解的生理事件相关的神经炎症和BBB破坏发生在急性时间点后插入UMEA。
Chronically implanted microelectrodes in the neural tissue elicit inflammatory responses that are time varying and have been shown to depend on multiple factors. Among these factors, blood brain barrier (BBB)-disruption has been hypothesized as one of the dominant factors resulting in electrode failure. A series of events that includes BBB and cell-membrane disruption occurs during electrode implantation that triggers multiple biochemical cascades responsible for microglial and astroglial activation, hemorrhage, edema, and release of pro-inflammatory neurotoxic cytokines that causes neuronal degeneration and dysfunction. Typically, microwire arrays and silicon probes are inserted slowly into the neural tissue whereas the silicon Utah MEAs (UMEA) are inserted at a high speed using a pneumatic inserter. In this work, we report the sequelae of electrode-implant induced cortical injury at various acute time points in UMEAs implanted in the brain tissue by quantifying the expression profile for key genes mediating the inflammatory response and tight junction (TJ) and adherens junction (AJ) proteins that form the BBB and are critical to the functioning of the BBB. Our results indicated upregulation of most pro-inflammatory genes relative to naïve controls for all time points. Expression levels for the genes that form the TJ and AJ were downregulated suggestive of BBB-dysfunction. Moreover, there was no significant difference between stab and implant groups suggesting the effects of UMEA insertion-related trauma in the brain tissue. Our results provide an insight into the physiological events related to neuroinflammation and BBB-disruption occurring at acute time-points following insertion of UMEAs.
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