Intraspinal stimulation with a silicon-based 3D chronic microelectrode array for bladder voiding in cats.

Intraspinal stimulation with a silicon-based 3D chronic microelectrode array for bladder voiding in cats.
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DOI:
10.1088/1741-2552/abca13
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发表时间:
2020-12-16
影响因子:
4
通讯作者:
Han M
Han M
中科院分区:
工程技术2区
文献类型:
--
作者:
Pikov V;McCreery DB;Han M

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膀胱功能障碍是脊髓损伤(SCI)患者的一个重要且未解决的问题。间歇性导尿不能提供排尿的意志控制,并有许多副作用。先前已经探索了脊髓的靶向电微刺激用于在实验性SCI的动物模型中恢复这种意志控制。在这里,我们继续发展的椎管内微刺激阵列技术,以评估其能力,提供更集中和可靠的膀胱控制的猫科动物模型。第一次,使用新型微加工工艺构建了机械坚固的椎管内多位点硅阵列,以提供定制设计的尖端几何形状和3D电极分布。在8只脊柱完整的动物中进行了长达6个月的长期植入,目标是S2骶髓中的背侧灰质连合区域,已知该区域参与膀胱逼尿肌和尿道外括约肌之间的协调。该区域约有三分之一的电极部位产生了与排尿相关的反应。脊髓横断(SCT)后,在8只动物中的一只动物中进一步评价刺激的有效性。我们观察到膀胱对刺激的反应性在横断后1个月开始增加,这可能是由于脊髓回路的脊髓上去抑制和/或脊髓膀胱传入神经的肥大和过度兴奋。3D脊柱内微刺激阵列可以长期植入,并对完整脊髓中和SCT后的膀胱排尿提供有益效果。然而,需要进一步的研究来评估开发的椎管内微刺激阵列在最终人类翻译之前的长期可靠性和安全性。
Bladder dysfunction is a significant and largely unaddressed problem for people living with spinal cord injury (SCI). Intermittent catheterization does not provide volitional control of micturition and has numerous side effects. Targeted electrical microstimulation of the spinal cord has been previously explored for restoring such volitional control in the animal model of experimental SCI. Here, we continue the development of the intraspinal microstimulation array technology to evaluate its ability to provide more focused and reliable bladder control in the feline animal model. For the first time, a mechanically robust intraspinal multisite silicon array was built using novel microfabrication processes to provide custom-designed tip geometry and 3D electrode distribution. Long-term implantation was performed in eight spinally intact animals for a period up to 6 months, targeting the dorsal gray commissure area in the S2 sacral cord that is known to be involved in the coordination between the bladder detrusor and the external urethral sphincter. About one third of the electrode sites in the that area produced micturition-related responses. The effectiveness of stimulation was further evaluated in one of eight animals after spinal cord transection (SCT). We observed increased bladder responsiveness to stimulation starting at 1 month post-transection, possibly due to supraspinal disinhibition of the spinal circuitry and/or hypertrophy and hyperexcitability of the spinal bladder afferents. 3D intraspinal microstimulation arrays can be chronically implanted and provide a beneficial effect on the bladder voiding in the intact spinal cord and after SCT. However, further studies are required to assess longer-term reliability and safety of the developed intraspinal microstimulation array prior to eventual human translation.
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