Delayed decompression exacerbates ischemia-reperfusion injury in cervical compressive myelopathy
Pia M. Vidal, Spyridon K. Karadimas, Antigona Ulndreaj, Alex M. Laliberte, Lindsay Tetreault, Stefania Forner, Jian Wang, Warren D. Foltz, Michael G. Fehlings
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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Research Article Inflammation Neuroscience

Delayed decompression exacerbates ischemia-reperfusion injury in cervical compressive myelopathy

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 10

Early surgical decompression improves upper extremity function.

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Early surgical decompression improves upper extremity function. (A) Earl...
(A) Early surgical decompression improves muscle/grip strength as assessed with the wire hang test. The latency to fall from the grid was significantly increased in the DCM-E + Dec group compared with the DCM-E group at the 1-, 2-, and 5-week time points. *P < 0.05, two-way ANOVA. Open squares at the –1w (1 week before surgical decompression) denotes all the animals before decompression. (B) No significant changes were observed in the group that underwent delayed surgery at any time point. (C) Representative images of DCM animals performing the wire hang test. The white arrows indicate different ways that decompressed animals hold onto the grid with the 4 limbs. The number of animals used was as follows: DCM-E group before surgical decompression (n = 15); DCM-E (n = 7); DCM-E + Dec (n = 8); DCM-D group before surgical decompression (n = 17), DCM-D (n = 9); DCM-D + Dec (n = 8). The dot plot at each time point represents the mean of 3 measurements per animal. (D) Manual dexterity using the Capellini handling test was measured as the time the animals spent eating a piece of 2.6-cm-long pasta. The DCM-E group before decompression experienced a significant increase in the time spent eating the pasta compared with naive animals. **P < 0.01, one-way ANOVA. The DCM-E + Dec group spent less time eating the pasta compared with the DCM-E group, at the 3-day, 4-day, and 5-week time points. *P < 0.05, one-way ANOVA. (E) Mice in the DCM-D group spent more time eating pasta, compared with naive animals. *P < 0.05, one-way ANOVA. However, no significant changes were detected at any time point after decompression. (F) Representative images of DCM animals performing the Capellini handling test. Some abnormal eating patterns were observed in DCM animals, such as head tilt and grabbing the pasta with 1 forepaw and hind limb on the floor. Naive animals (n = 3); DCM-E group before surgical decompression (n = 12); DCM-E + Dec (n = 7–12); DCM-D group before surgical decompression (n = 8); DCM-D + Dec (n = 7–8). The dot plot at each time point represents the mean of 3 measurements per animal. The results are presented as mean ± SEM. DCM, degenerative cervical myelopathy; Dec, decompression; DCM-E, age-matched early sham decompressed group; DCM-D, age-matched delayed sham decompressed group; w, weeks.