The effect of resveratrol on neurodegeneration and blood brain barrier stability surrounding intracortical microelectrodes
The effect of resveratrol on neurodegeneration and blood brain barrier stability surrounding intracortical microelectrodes
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DOI：
10.1016/j.biomaterials.2013.05.035
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发表时间：
2013-09-01
期刊：
影响因子：
14
通讯作者：
Capadona, Jeffrey R.
中科院分区：
文献类型：
--
作者：
Potter, Kelsey A.;Buck, Amy C.;Capadona, Jeffrey R.
目前的研究试图阐明一种可能介导神经炎症的生物学机制，并降低皮质内微电极-组织界面的血脑屏障稳定性和神经元活性。在这里，我们重点介绍了促炎活性氧物种的作用。具体地说，植入皮质内微电极的成年大鼠在手术前一天和手术前一天都系统地注射了抗氧化剂白藜芦醇。在植入后2周或4周处死动物，对微电极的神经炎性和神经退行性反应进行组织学分析。在植入后两周，我们发现白藜芦醇处理的动物表现出抑制活性氧积累和血脑屏障不稳定性，并伴有皮质内微电极-组织界面神经元密度的增加。植入四周后，与未处理的对照组相比，接受白藜芦醇治疗的动物显示出难以区分的活性氧物种和神经元核密度的标记水平。然而，在剩下的神经元中，白藜芦醇处理的动物在植入后两周和四周显示出与对照动物相比退化神经元密度的减少。初步的机制评估表明，抗氧化酶和Toll样受体4的表达在促进小胶质细胞激活和神经退行性炎症途径的传播中发挥了作用。总而言之，我们的数据表明，短期内活性氧积累的减弱和血脑屏障的不稳定性可以导致植入的皮质内微电极周围神经元存活率的长期改善，同时还可以确定潜在的治疗靶点，以减少皮质内微电极介导的慢性神经变性。爱思唯尔有限公司出版。
The current study seeks to elucidate a biological mechanism which may mediate neuroinflammation, and decreases in both blood-brain barrier stability and neuron viability at the intracortical microelectrode-tissue interface. Here, we have focused on the role of pro-inflammatory reactive oxygen species. Specifically, adult rats implanted within intracortical microelectrodes were systemically administered the anti-oxidant, resveratrol, both the day before and the day of surgery. Animals were sacrificed at two or four weeks post-implantation for histological analysis of the neuroinflammatory and neurodegenerative responses to the microelectrode. At two weeks post-implantation, we found animals treated with resveratrol demonstrated suppression of reactive oxygen species accumulation and blood-brain barrier instability, accompanied with increased density of neurons at the intracortical microelectrode-tissue interface. Four weeks post-implantation, animals treated with resveratrol exhibited indistinguishable levels of markers for reactive oxygen species and neuronal nuclei density in comparison to untreated control animals. However, of the neurons that remained, resveratrol treated animals were seen to display reductions in the density of degenerative neurons compared to control animals at both two and four weeks post-implantation. Initial mechanistic evaluation suggested the roles of both anti-oxidative enzymes and toll-like receptor 4 expression in facilitating microglia activation and the propagation of neurodegenerative inflammatory pathways. Collectively, our data suggests that short-term attenuation of reactive oxygen species accumulation and blood-brain barrier instability can result in prolonged improvements in neuronal viability around implanted intracortical microelectrodes, while also identifying potential therapeutic targets to reduce chronic intracortical microelectrode-mediated neurodegeneration. Published by Elsevier Ltd.