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Delayed decompression exacerbates ischemia-reperfusion injury in cervical compressive myelopathy
Pia M. Vidal, … , Warren D. Foltz, Michael G. Fehlings
Pia M. Vidal, … , Warren D. Foltz, Michael G. Fehlings
Published June 2, 2017
Citation Information: JCI Insight. 2017;2(11):e92512. https://doi.org/10.1172/jci.insight.92512.
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Research Article Inflammation Neuroscience

Delayed decompression exacerbates ischemia-reperfusion injury in cervical compressive myelopathy

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Abstract

Degenerative cervical myelopathy (DCM) is the most common progressive nontraumatic spinal cord injury. The most common recommended treatment is surgical decompression, although the optimal timing of intervention is an area of ongoing debate. The primary objective of this study was to assess whether a delay in decompression could influence the extent of ischemia-reperfusion injury and alter the trajectory of outcome in DCM. Using a DCM mouse model, we show that decompression acutely led to a 1.5- to 2-fold increase in levels of inflammatory cytokines within the spinal cord. Delayed decompression was associated with exacerbated reperfusion injury, astrogliosis, and poorer neurological recovery. Additionally, delayed decompression was associated with prolonged elevation of inflammatory cytokines and an exacerbated peripheral monocytic inflammatory response (P < 0.01 and 0.001). In contrast, early decompression led to resolution of reperfusion-mediated inflammation, neurological improvement, and reduced hyperalgesia. Similar findings were observed in subjects from the CSM AOSpine North America and International studies, where delayed decompressive surgery resulted in poorer neurological improvement compared with patients with an earlier intervention. Our data demonstrate that delayed surgical decompression for DCM exacerbates reperfusion injury and is associated with ongoing enhanced levels of cytokine expression, microglia activation, and astrogliosis, and paralleled with poorer neurological recovery.

Authors

Pia M. Vidal, Spyridon K. Karadimas, Antigona Ulndreaj, Alex M. Laliberte, Lindsay Tetreault, Stefania Forner, Jian Wang, Warren D. Foltz, Michael G. Fehlings

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Figure 1

Experimental design.

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Experimental design.
(A) Representative intraoperative images of the spi...
(A) Representative intraoperative images of the spinal cord before material implantation (before DCM), of a compressed animal before and after decompression (from left to right, respectively). (B and C) Scheme of the time points assessed for early and delayed decompression. The time is provided based on (i) weeks after induction of DCM and (ii) after decompression. In these timelines, time 0 refers to either the time of material implantation (see weeks after DCM) or the time of decompression (see weeks after Dec). Mice in the early-decompressed group were operated at 6 weeks after DCM by receiving decompression (DCM-E + Dec) or a sham decompression (DCM-E) (B). Similarly, the delayed-decompressed group received decompression (DCM-D + Dec) or sham decompression (DCM-D), but at 12 weeks after material implantation (C). Both groups were sacrificed at 24 hours and 2 and 5 weeks after their decompressive surgery, and tissues of interest were collected. Neurobehavioral assessment was carried out until 5 weeks after surgery. DCM, degenerative cervical myelopathy; Dec, decompression; DCM-E, age-matched early sham decompressed group; DCM-D, age-matched delayed sham decompressed group.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

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