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Blood brain barrier (BBB)-disruption in intracortical silicon microelectrode implants
Biomaterials ( IF 12.8 ) Pub Date : 2018-02-20 , DOI: 10.1016/j.biomaterials.2018.02.036
Cassie Bennett , Malaroviyam Samikkannu , Farrah Mohammed , W. Dalton Dietrich , Suhrud M. Rajguru , Abhishek Prasad

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.



中文翻译:

皮质内硅微电极植入物中的血脑屏障(BBB)破坏

长期植入神经组织中的微电极会引起时变的炎症反应,并显示出取决于多种因素。在这些因素中,血脑屏障(BBB)的破坏被认为是导致电极故障的主要因素之一。电极植入过程中发生了一系列事件,包括血脑屏障和细胞膜破坏,这些事件触发了多个生物化学级联反应,导致小胶质细胞和星形胶质细胞活化,出血,水肿和促炎性神经毒性细胞因子释放,从而引起神经元变性和功能障碍。通常,将微线阵列和硅探针缓慢插入神经组织,而使用气动插入器将硅犹他州MEA(UMEA)高速插入。在这项工作中,我们通过量化介导形成炎症反应和紧密连接(TJ)和粘附连接(AJ)蛋白质的关键基因的表达谱,报道了植入电极的UMEA中在不同急性时间点电极植入物引起的皮质损伤的后遗症BBB的功能,对于BBB的功能至关重要。我们的结果表明在所有时间点上,大多数促炎基因相对于单纯对照均上调。形成TJ和AJ的基因的表达水平被下调,提示BBB功能障碍。此外,刺伤组和植入物组之间没有显着差异,表明UMEA插入相关创伤对脑组织的影响。

更新日期:2018-02-21
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