Jung James, Hahn Peter, Choi Bernard, Mozaffar Tahseen, Gupta Ranjan
Department of Orthopaedic Surgery, University of California, 2226 Gillespie Neuroscience Research Facility, Irvine, CA 92697. E-mail address for R. Gupta:
Department of Biomedical Engineering, University of California, Irvine, CA 92697.
J Bone Joint Surg Am. 2014 Jun 4;96(11):897-906. doi: 10.2106/JBJS.M.01116.
Chronic nerve compression neuropathies result in decreased blood flow at the site of compression. Surgical decompression of the nerve often has variable postoperative results. The current study examines whether the timing of surgical intervention is an important variable in reversing the compression-induced ischemia and associated changes in biochemical markers.
An established model of chronic nerve compression injury was created in 100 C57BL/6 mice, and serial electrophysiological examinations were used to confirm the creation of a chronic nerve compression injury. Laser speckle imaging was used to measure neural blood flow. Nerves in the animals that did not undergo decompression were harvested at two, four, and six weeks after injury and analyzed for hypoxia-inducible factor 1α (HIF1α), catalase, superoxide dismutase (SOD), and matrix metalloproteinases (MMPs) 2 and 9. Surgical decompression in other animals was performed at either an early (two-week) or late (six-week) time point after injury, with specimens harvested at multiple time points after decompression. One-way analysis of variance with Bonferroni correction was performed.
Chronic nerve compression injury initially induced hyperemia (1.37 ± 0.50 times that in the contralateral, uninjured nerve) followed by a decline in neural blood flow by four weeks (0.66 ± 0.14, p = 0.0313). In parallel, HIF1α, catalase, and SOD were elevated early after compression, whereas extracellular matrix-altering proteins were elevated later in the disease. Although early decompression yielded a return of blood flow to a hyperemic state (1.35 ± 0.16, p = 0.0057), late decompression did not result in reversal of the abnormal neurovascular flow. With late decompression, an MMP9-mediated structural alteration of the extracellular matrix was seen, producing irreversible changes in blood flow parameters. Although nerve conduction velocity measurements returned to normal two weeks after decompression irrespective of the timing of the surgical intervention, distal latency returned to normal only after early decompression (0.97 ± 0.06 msec compared with 1.22 ± 0.06 msec for late decompression, p = 0.009).
Chronic nerve compression injuries decreased neurovascular flow and induced ischemia by upregulating HIF1α, catalase, and MMP9. Early surgical intervention offered better return to normal electrophysiological parameters compared with late intervention.
These data present a clinical correlate to the variable functional outcomes seen following surgical release of chronic nerve compression injuries and provide early support for using distal latency as a predictor of outcomes following surgical release.
慢性神经压迫性神经病变会导致压迫部位的血流减少。神经外科减压手术的术后效果往往不尽相同。本研究旨在探讨手术干预时机是否是逆转压迫性缺血及相关生化标志物变化的重要变量。
在100只C57BL/6小鼠中建立慢性神经压迫损伤模型，并通过系列电生理检查来确认慢性神经压迫损伤的形成。采用激光散斑成像测量神经血流。在损伤后2周、4周和6周处死未接受减压的动物，取神经样本，分析其中缺氧诱导因子1α（HIF1α）、过氧化氢酶、超氧化物歧化酶（SOD）以及基质金属蛋白酶（MMP）2和9的含量。对其他动物在损伤后的早期（2周）或晚期（6周）进行手术减压，并在减压后的多个时间点取样本。采用单因素方差分析并进行Bonferroni校正。
慢性神经压迫损伤最初会引起充血（是对侧未损伤神经的1.37±0.50倍），随后在4周时神经血流下降（0.66±0.14，p = 0.0313）。与此同时，HIF1α、过氧化氢酶和SOD在压迫早期升高，而改变细胞外基质的蛋白在疾病后期升高。尽管早期减压使血流恢复到充血状态（1.35±0.16，p = 0.0057），但晚期减压并未使异常的神经血管血流逆转。晚期减压时，可见MMP9介导的细胞外基质结构改变，导致血流参数发生不可逆变化。尽管无论手术干预时机如何，减压后2周神经传导速度测量值均恢复正常，但仅早期减压后远端潜伏期恢复正常（0.97±0.06毫秒，晚期减压为1.22±0.06毫秒，p = 0.009）。
慢性神经压迫损伤通过上调HIF1α、过氧化氢酶和MMP9降低神经血管血流并诱导缺血。与晚期干预相比，早期手术干预能使电生理参数更好地恢复正常。
这些数据与慢性神经压迫损伤手术松解后功能结果的差异存在临床相关性，并为将远端潜伏期用作手术松解后结果的预测指标提供了早期支持。
