title: Early Surgical Decompression Restores Neurovascular Blood Flow and Ischemic Parameters in an in Vivo Animal Model of Nerve Compression Injury.
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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Orthopaedic Surgery, University of California, 2226 Gillespie Neuroscience Research Facility, Irvine, CA 92697. E-mail address for R. Gupta: ranjang@uci.edu.
authors.forename: James
authors.initials: J
authors.lastname: Jung
authors.affiliation: Department of Orthopaedic Surgery, University of California, 2226 Gillespie Neuroscience Research Facility, Irvine, CA 92697. E-mail address for R. Gupta: ranjang@uci.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Hahn
authors.affiliation: Department of Biomedical Engineering, University of California, Irvine, CA 92697.
authors.forename: Bernard
authors.initials: B
authors.lastname: Choi
authors.affiliation: Department of Orthopaedic Surgery, University of California, 2226 Gillespie Neuroscience Research Facility, Irvine, CA 92697. E-mail address for R. Gupta: ranjang@uci.edu.
authors.forename: Tahseen
authors.initials: T
authors.lastname: Mozaffar
authors.affiliation: Department of Orthopaedic Surgery, University of California, 2226 Gillespie Neuroscience Research Facility, Irvine, CA 92697. E-mail address for R. Gupta: ranjang@uci.edu.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Gupta
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D019299:Decompression, Surgical; D004195:Disease Models, Animal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007511:Ischemia / Q000209:etiology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009408:Nerve Compression Syndromes / Q000150:complications* / Q000601:surgery*; D009431:Neural Conduction; D059348:Peripheral Nerve Injuries / Q000601:surgery*; D012584:Sciatic Nerve / Q000098:blood supply* / Q000601:surgery*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D002374:Catalase; D020780:Matrix Metalloproteinase 9