James Jung1, Peter Hahn1, Bernard Choi2, Tahseen Mozaffar1, Ranjan Gupta1. 1. Department of Orthopaedic Surgery, University of California, 2226 Gillespie Neuroscience Research Facility, Irvine, CA 92697. E-mail address for R. Gupta: ranjang@uci.edu. 2. Department of Biomedical Engineering, University of California, Irvine, CA 92697.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. CLINICAL RELEVANCE: 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.
BACKGROUND: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. METHODS: 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. RESULTS: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). CONCLUSIONS: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. CLINICAL RELEVANCE: 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.
Authors: Michael Warren Keith; Victoria Masear; Kevin C Chung; Kent Maupin; Michael Andary; Peter C Amadio; William C Watters; Michael J Goldberg; Robert H Haralson; Charles M Turkelson; Janet L Wies; Richard McGowan Journal: J Bone Joint Surg Am Date: 2009-10 Impact factor: 5.284