A progressive compression model of thoracic spinal cord injury in mice： function assessment and pathological changes in spinal cord

Non-traumatic injury accounts for approximately half of clinical spinal cord injury, including chronic spinal cord compression. However, previous rodent spinal cord compression models are mainly designed for rats, few are available for mice. Our aim is to develop a thoracic progressive compression mice model of spinal cord injury. In this study, adult wild-type C57BL/6 mice were divided into two groups： in the surgery group, a screw was inserted at T9 lamina to compress the spinal cord, and the compression was increased by turning it further into the canal（0.2 mm） post-surgery every 2 weeks up to 8 weeks. In the control group, a hole was drilled into the lamina without inserting a screw. The results showed that Basso Mouse Scale scores were lower and gait worsened. In addition, the degree of hindlimb dysfunction in mice was consistent with the degree of spinal cord compression. The number of motor neurons in the anterior horn of the spinal cord was reduced in all groups of mice, whereas astrocytes and microglia were gradually activated and proliferated. In conclusion, this progressive compression of thoracic spinal cord injury in mice is a preferable model for chronic progressive spinal cord compression injury.

Assessment of hindlimb motor recovery affer severe thoracic spinal cord injury in rats: classification of CatWalk XT■ gait analysis parameters

Assessment of locomotion recovery in preclinical studies of experimental spinal cord injury remains challenging. We studied the CatWalk XT■gait analysis for evaluating hindlimb functional recovery in a widely used and clinically relevant thoracic contusion/compression spinal cord injury model in rats. Rats were randomly assigned to either a T9 spinal cord injury or sham laminectomy. Locomotion recovery was assessed using the Basso, Beattie, and Bresnahan open field rating scale and the CatWalk XT■gait analysis. To determine the potential bias from weight changes, corrected hindlimb(H) values(divided by the unaffected forelimb(F) values) were calculated. Six weeks after injury, cyst formation, astrogliosis, and the deposition of chondroitin sulfate glycosaminoglycans were assessed by immunohistochemistry staining. Compared with the baseline, a significant spontaneous recovery could be observed in the CatWalk XT■parameters max intensity, mean intensity, max intensity at%, and max contact mean intensity from 4 weeks after injury onwards. Of note, corrected values(H/F) of CatWalk XT■parameters showed a significantly less vulnerability to the weight changes than absolute values, specifically in static parameters. The corrected CatWalk XT■parameters were positively correlated with the Basso, Beattie, and Bresnahan rating scale scores, cyst formation, the immunointensity of astrogliosis and chondroitin sulfate glycosaminoglycan deposition. The CatWalk XT■gait analysis and especially its static parameters, therefore, seem to be highly useful in assessing spontaneous recovery of hindlimb function after severe thoracic spinal cord injury. Because many CatWalk XT■parameters of the hindlimbs seem to be affected by body weight changes, using their corrected values might be a valuable option to improve this dependency.

Ninjurin-1: a biomarker for reflecting the process of neuroinflammation after spinal cord injury

Previous studies have shown that Ninjurin-1 participates in cell trafficking and axonal growth following central and peripheral nervous system neuroinflammation.But its precise roles in these processes and involvement in spinal cord injury pathophysiology remain unclear.Western blot assay revealed that Ninjurin-1 levels in rats with spinal cord injury exhibited an upregulation until day 4 post-injury and slightly decreased thereafter compared with sham controls.Immunohistochemistry analysis revealed that Ninjurin-1 immunoreactivity in rats with spinal cord injury sharply increased on days 1 and 4 post-injury and slightly decreased on days 7 and 21 post-injury compared with sham controls.Ninjurin-1 immunostaining was weak in vascular endothelial cells, ependymal cells, and some glial cells in sham controls while it was relatively strong in macrophages, microglia, and reactive astrocytes.These findings suggest that a variety of cells, including vascular endothelial cells, macrophages, and microglia, secrete Ninjurin-1 and they participate in the pathophysiology of compression-induced spinal cord injury.All experimental procedures were approved by the Care and Use of Laboratory Animals of Jeju National University(approval No.2018-0029) on July 6, 2018.

Exploratory use of ultrasound to determine whether demyelination following carpal tunnel syndrome co-exists with axonal degeneration

Carpal tunnel syndrome （CTS） accompanied by secondary axonal degeneration cannot be clearly dis- criminated using the current cross-validated ultrasound severity classification system. This study aimed at exploring cut-off values of ultrasound parameters, including wrist cross-sectional area （W-CSA）, wrist perimeter （W-P）, ratio of cross-sectional area （R-CSA） and perimeter （R-P）, changes of CSA and P from wrist to one third distal forearm （△CSA＆AP） for differentiation. Seventy-three patients （13 male and 60 female） were assigned into group A （demyelination only, n = 40） and group B （demyelination with secondary axonal degeneration, n = 33） based on the outcomes of nerve conduction studies （NCS）. Receiver Operative Characteristics （ROC） curves were plotted to obtain sensitivity, specificity, and accuracy of cut- off values for all the ultrasound parameters. The overall identified cut-off values （W-CSA 12.0 mm2, W-P 16.27 mm, R-CSA 1.85, R-P 1.48, △CSA 6.98 mm2, △P 5.77 mm） had good sensitivity （77.1-88.6%）, fair specificity （40-62.2%） and fair-to-good accuracy （0.676-0.758）. There were also significant differences in demographics （age and severity gradation, P 〈 0.001）, NCS findings （wrist motor latency and conduction velocity, P 〈 0.0001; wrist motor amplitude, P 〈 0.05; distal sensory latency, P 〈 0.05; sensory amplitude, P 〈 0.001） and ultrasound measurements （W-CSA, W-P, R-CSA, R-P, △CSA＆△P, P 〈 0.05） between groups. These findings suggest that ultrasound can be potentially used to differentiate demyelinating CTS with sec- ondary axonal degeneration and provide better treatment guidance.

Anterior subcutaneous transposition of the ulnar nerve improves neurological function in patients with cubital tunnel syndrome

Although several surgical procedures exist for treating cubital tunnel syndrome, the best surgical option remains controversial. To evaluate the efficacy of anterior subcutaneous transposition of the ulnar nerve in patients with moderate to severe cubital tunnel syndrome and to analyze prognostic factors, we retrospectively reviewed 62 patients（65 elbows） diagnosed with cubital tunnel syndrome who underwent anterior subcutaneous transposition. Preoperatively, the initial severity of the disease was evaluated using the Mc Gowan scale as modified by Goldberg： 18 patients（28%） had grade IIA neuropathy, 20（31%） had grade IIB, and 27（42%） had grade III. Postoperatively, according to the Wilson ＆ Krout criteria, treatment outcomes were excellent in 38 patients（58%）, good in 16（25%）, fair in 7（11%）, and poor in 4（6%）, with an excellent and good rate of 83%. A negative correlation was found between the preoperative Mc Gowan grade and the postoperative Wilson ＆ Krout score. The patients having fair and poor treatment outcomes had more advanced age, lower nerve conduction velocity, and lower action potential amplitude compared with those having excellent and good treatment outcomes. These results suggest that anterior subcutaneous transposition of the ulnar nerve is effective and safe for the treatment of moderate to severe cubital tunnel syndrome, and initial severity, advancing age, and electrophysiological parameters can affect treatment outcome.

Bee venom acupuncture reduces neuroinflammation modulating microglia/macrophage phenotype polarization in spinal cord injury compression model

Aim: The present study aimed to examine whether apipuncture (stimulation of acupuncture points with bee venom)at ST36 and GV3 acupoints promotes neuroprotection and reduces neuroinflammation by modulating M1 and M2 phenotype polarization.Methods: Wistar rats were treated with bee venom (BV) (0.08 mg/kg) injection at acupoints ST36 and GV3 [BV (ST36 + GV3)-spinal cord injury (SCI)] or BV injection at non-acupoints [BV (NP)-SCI] or no treatment (CTL-SCI)after SCI by compression. The spinal cord mRNA expression of iNOS, Arg-1 and TGF-β was measured by real time PCR and the levels of IBA-1;BCL-2;NeuN e CNPase was measured by western blotting. Locomotor performance was measured by Basso, Beattie, and Bresnahan (BBB) and grid-walking tests.Results: Apipuncture treatment was able to (1) ameliorate locomotor performance;(2) reduce inflammatory markers (Cox-2 levels) and activation of microglia and macrophages;(3) reduce the polarization of the M1 phenotype marker (iNOS) and increase M2 (Arg-1 and TGF-β) phenotypic markers;(4) promote neuroprotection by reducing the death of neurons and oligodendrocytes;and (5) increase the expression of the anti-apoptotic factor BCL-2.Conclusion: Apipuncture treatment induces locomotor recovery and neuroprotection after the compression model of spinal cord injury. Further, it reduces neuroinflammation by decreasing M1 polarization and increasing M2 phenotype.