Thoracolumbar epidural stimulation effects on bladder and bowel function in uninjured and chronic transected anesthetized rats.

Thoracolumbar epidural stimulation effects on bladder and bowel function in uninjured and chronic transected anesthetized rats.
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DOI:
10.1038/s41598-022-06011-2
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发表时间:
2022-02-08
期刊:
影响因子:
4.6
通讯作者:
Hubscher CH
Hubscher CH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hoey RF;Medina-Aguiñaga D;Khalifa F;Ugiliweneza B;Wang D;Zdunowski S;Fell J;Naglah A;El-Baz AS;Herrity AN;Harkema SJ;Hubscher CH

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临床前研究表明,在骨盆和阴部神经输入/输出(L5-S1)水平的脊髓硬膜外刺激(scES)改变膀胱和肠的储存和/或排空功能。进行当前映射实验以研究在乌拉坦麻醉下雄性和雌性大鼠中在腹下神经输入/输出(T13-L2)水平上的scES功效。与L5-S1 scES一样,T13-L2 scES在选定的频率和刺激强度下在未受伤的雌性大鼠中产生了收缩间期(ICI)的增加,但在慢性T9横断大鼠中产生了短潜伏期的空隙,以及所有组中直肠活动的减少。然而,在延长的ICI期间的逼尿肌压力(即,尿潴留)保持在低压下,并且不像L5-S1 scES所见的那样升高,这是一种对于转化为临床至关重要的效果,因为高填充压力可能损害肾脏。此外,T13-L2 scES显示通过增加膀胱活动刺激切断后排尿,同时还直接抑制尿道外括约肌,这是克服逼尿肌-括约肌协同失调所必需的模式。此外,在T13-L2处选择的scES参数也增加了所有组中的远端结肠活动。总之,目前的研究结果表明,针对膀胱和肠的scES的优化可能需要在不同位置处的多个电极群组,其靶向协调交感神经、副交感神经和躯体输出的电路。
Pre-clinical studies have shown that spinal cord epidural stimulation (scES) at the level of pelvic and pudendal nerve inputs/outputs (L5-S1) alters storage and/or emptying functions of both the bladder and bowel. The current mapping experiments were conducted to investigate scES efficacy at the level of hypogastric nerve inputs/outputs (T13-L2) in male and female rats under urethane anesthesia. As found with L5-S1 scES, T13-L2 scES at select frequencies and intensities of stimulation produced an increase in inter-contraction interval (ICI) in non-injured female rats but a short-latency void in chronic T9 transected rats, as well as reduced rectal activity in all groups. However, the detrusor pressure during the lengthened ICI (i.e., urinary hold) remained at a low pressure and was not elevated as seen with L5-S1 scES, an effect that’s critical for translation to the clinic as high fill pressures can damage the kidneys. Furthermore, T13-L2 scES was shown to stimulate voiding post-transection by increasing bladder activity while also directly inhibiting the external urethral sphincter, a pattern necessary to overcome detrusor-sphincter dyssynergia. Additionally, select scES parameters at T13-L2 also increased distal colon activity in all groups. Together, the current findings suggest that optimization of scES for bladder and bowel will likely require multiple electrode cohorts at different locations that target circuitries coordinating sympathetic, parasympathetic and somatic outputs.
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