Gumbel Jason H, Hubscher Charles H
Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, Kentucky, USA.
Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, Kentucky, USA.
Neurotrauma Rep. 2022 Apr 26;3(1):190-198. doi: 10.1089/neur.2022.0014. eCollection 2022.
Spinal cord injury (SCI) significantly impacts many systems attributable to disrupted autonomic regulation of the body. Of these disruptions, excessive production/passage of urine (polyuria) has been understudied. Pre-clinical animal studies investigating SCI-induced polyuria have been carried out in T8-T10 spinal-level contusive injuries, which directly impacts both supraspinal sympathetic inputs to the spinal circuitry mediating kidney function as well as local networks including pre-ganglionic sympathetic fibers to the kidney. The current study utilizes a higher-level (T3) contusion to narrow the potential source(s) of damage that induce(s) polyuria. Metabolic cage 24-h urine collections demonstrated that, starting 1 week post-SCI and lasting chronically through 6 weeks post-SCI, T3 contused adult male rats had a significant increase in void volume relative to pre-injury and surgical sham controls. Subsequent examination of previously identified biomarkers revealed levels reflecting the presence of polyuria. For example, urine atrial natriuretic peptide levels were significantly increased at 6 weeks post-SCI compared to baseline, and serum arginine vasopressin (AVP) levels were significantly decreased. Further, there was a significant decrease post-injury relative to shams in the number of AVP-labeled cells within the suprachiasmatic nucleus, a hypothalamic region responsible for significant disruptions of circadian rhythmicity post-SCI, including loss of the diurnal variation of AVP production, which clinical studies have identified as contributing to the emergence of nocturia after SCI. Together, the current results demonstrate that SCI-induced polyuria is present after a T3-level SCI, indicating that damage of descending supraspinal circuitries precipitates dysfunction of homeostatic mechanisms involved in salt and water balance.
脊髓损伤（SCI）会对许多系统产生重大影响，这归因于身体自主调节功能的紊乱。在这些功能紊乱中，尿液过度生成/排出（多尿）的研究较少。针对SCI诱导的多尿进行的临床前动物研究是在T8 - T10脊髓水平的挫伤性损伤模型中开展的，这种损伤直接影响到调节肾功能的脊髓回路的脊髓上交感神经输入以及包括肾节前交感神经纤维在内的局部网络。本研究采用更高水平（T3）的挫伤来缩小诱导多尿的潜在损伤源。代谢笼24小时尿液收集显示，从SCI后1周开始并持续至SCI后6周，T3挫伤的成年雄性大鼠的排尿量相对于损伤前和手术假对照有显著增加。随后对先前确定的生物标志物进行检测，结果显示了反映多尿存在的水平。例如，与基线相比，SCI后6周时尿心房利钠肽水平显著升高，而血清精氨酸加压素（AVP）水平显著降低。此外，与假手术组相比，损伤后视交叉上核内AVP标记细胞的数量显著减少，视交叉上核是下丘脑的一个区域，SCI后昼夜节律的显著紊乱与之相关，包括AVP分泌昼夜变化的丧失，临床研究已确定这是SCI后夜尿症出现的原因之一。总之，目前的结果表明，T3水平的SCI后会出现SCI诱导的多尿，这表明脊髓上下行通路的损伤会导致参与盐和水平衡的稳态机制功能障碍。
