Research Outputs

Now showing 1 - 3 of 3
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    Acute systemic white blood cell changes following Degenerative Cervical Myelopathy (DCM) in a Mouse Model
    (International Journal of Molecular Sciences, 2022) ; ;
    Ulndreaj, Antigona
    ;
    Hong, James
    ;
    Zhou, Cindy
    ;
    Fehlings, Michael
    Degenerative cervical myelopathy (DCM) is caused by age-related degeneration of the cervical spine, causing chronic spinal cord compression and inflammation. The aim of this study was to assess whether the natural progression of DCM is accompanied by hematological changes in the white blood cell composition. If so, these changes can be used for diagnosis complementing established imaging approaches and for the development of treatment strategies, since peripheral immunity affects the progression of DCM. Gradual compression of the spinal cord was induced in C57B/L mice at the C5-6 level. The composition of circulating white blood cells was analyzed longitudinally at four time points after induction of DCM using flow cytometry. At 12 weeks, serum cytokine levels were measured using a Luminex x-MAP assay. Neurological impairment in the mouse model was also assessed using the ladder walk test and CatWalk. Stepping function (* p < 0.05) and overground locomotion (*** p < 0.001) were impaired in the DCM group. Importantly, circulating monocytes and T cells were affected primarily at 3 weeks following DCM. T cells were two-fold lower in the DCM group (*** p < 0.0006), whereas monocytes were four-fold increased (*** p < 0.0006) in the DCM compared with the sham group. Our data suggest that changes in white blood cell populations are modest, which is unique to other spinal cord pathologies, and precede the development of neurobehavioral symptoms.
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    IgM immunoglobulin influences recovery after cervical spinal cord injury by modulating the IgG autoantibody response
    (Society for Neuroscience, 2021) ;
    Ulndreaj, Antigona
    ;
    Forgione, Nicole
    ;
    Hong, James
    ;
    Fehlings, Michael
    Spinal cord injury (SCI) results in the development of detrimental autoantibodies against the lesioned spinal cord. IgM immunoglobulin maintains homeostasis against IgG-autoantibody responses, but its effect on SCI recovery remains unknown. In the present study we investigated the role of IgM immunoglobulin in influencing recovery after SCI. To this end, we induced cervical SCI at the C6/C7 level in mice that lacked secreted IgM immunoglobulin [IgM-knock-out (KO)] and their wild-type (WT) littermate controls. Overall, the absence of secretory IgM resulted in worse outcomes as compared with WT mice with SCI. At two weeks after injury, IgM-KO mice had significantly more IgG antibodies, which fixed the complement system, in the injured spinal cord parenchyma. In addition to these findings, IgM-KO mice had more parenchymal T-lymphocytes as well as CD11b+ microglia/macrophages, which co-localized with myelin. At 10 weeks after injury, IgM-KO mice showed significant impairment in neurobehavioral recovery, such as deteriorated coordination, reduced hindlimb swing speed and print area. These neurobehavioral detriments were coupled with increased lesional tissue and myelin loss. Taken together, this study provides the first evidence for the importance of IgM immunoglobulin in modulating recovery after SCI and suggests that modulating IgM could be a novel therapeutic approach to enhance recovery after SCI.
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    Neuromotor decline is associated with gut dysbiosis following surgical decompression for Degenerative Cervical Myelopathy
    (Elsevier, 2024) ; ;
    Brockie, Sydney
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    Hong, James
    ;
    Zhou, Cindy
    ;
    Fehlings, Michael
    Degenerative cervical myelopathy (DCM) describes a spectrum of disorders that cause progressive and chronic cervical spinal cord compression. The clinical presentation can be complex and can include locomotor impairment, hand and upper extremity dysfunction, pain, loss of bladder and bowel function, as well as gastrointestinal dysfunction. Once diagnosed, surgical decompression is the recommended treatment for DCM patients with moderate to severe impairment. Our body is composed of a large community of microorganisms, known as the microbiota. Traumatic and nontraumatic spinal cord injuries (SCIs) can induce changes in the gut microbiota and gut microbiota derived metabolites. These changes have been reported as important disease-modifying factors after injury. However, whether gut dysbiosis is associated with functional neurological recovery after surgical decompression has not been examined to date. Here, DCM was induced in C57BL/6 mice by implanting an aromatic polyether material underneath the C5–6 laminae. The extent of gut dysbiosis was assessed by gas chromatography and 16S rRNA sequencing from fecal samples before and after decompression. Neuromotor activity was assessed using the Catwalk test. Our results show that DCM pre- and post- surgical decompression is associated with gut dysbiosis, without altering short chain fatty acids (SCFAs) levels. Significant differences in Clostridia, Verrumicrobiae, Lachnospiracea, Firmicutes, Bacteroidales, and Clostridiaceae were observed between the DCM group (before decompression) and after surgical decompression (2 and 5 weeks). The changes in gut microbiota composition correlated with locomotor features of the Catwalk. For example, a longer duration of ground contact and dysfunctional swing in the forelimbs, were positively correlated with gut dysbiosis. These results show for the first time an association between gut dysbiosis and locomotor deterioration after delayed surgical decompression. Thus, providing a better understanding of the extent of changes in microbiota composition in the setting of DCM pre- and postsurgical decompression.