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Background: Reduced pelvic limb reflexes in dogs with spinal cord injury typically suggests a lesion of the L4-S3 spinal cord segments. However, pelvic limb reflexes might also be reduced in dogs with a T3-L3 myelopathy and concurrent spinal shock., Hypothesis/objectives: We hypothesized that statistical models could be used to identify clinical variables associated with spinal shock in dogs with spinal cord injuries., Animals: Cohort of 59 dogs with T3-L3 myelopathies and spinal shock and 13 dogs with L4-S3 myelopathies., Methods: Data used for this study were prospectively entered by partner institutions into the International Canine Spinal Cord Injury observational registry between October 2016 and July 2019. Univariable logistic regression analyses were performed to assess the association between independent variables and the presence of spinal shock. Independent variables were selected for inclusion in a multivariable logistic regression model if they had a significant effect (P ≤ .1) on the odds of spinal shock in univariable logistic regression., Results: The final multivariable model included the natural log of weight (kg), the natural log of duration of clinical signs (hours), severity (paresis vs paraplegia), and pelvic limb tone (normal vs decreased/absent). The odds of spinal shock decreased with increasing weight (odds ratio [OR] = 0.28, P = .09; confidence interval [CI] 0.07-1.2), increasing duration (OR = 0.44, P = .02; CI 0.21-0.9), decreased pelvic limb tone (OR = 0.04, P = .003; CI 0.01-0.36), and increased in the presence of paraplegia (OR = 7.87, P = .04; CI 1.1-56.62)., Conclusions and Clinical Importance: A formula, as developed by the present study and after external validation, could be useful for assisting clinicians in determining the likelihood of spinal shock in various clinical scenarios and aid in diagnostic planning., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Traumatic spinal cord injury (SCI) results in sensory and motor function impairment and may cause a substantial social and economic burden. For the implementation of novel treatment strategies, parallel development of objective tools evaluating spinal cord (SC) integrity during motor function recovery (MFR) is needed. Diffusion tensor imaging (DTI) enables in vivo microstructural assessment of SCI., Methods: In the current study, temporal evolvement of DTI metrics during MFR were examined; therefore, values of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured in a population of 17 paraplegic dogs with naturally-occurring acute SCI showing MFR within 4 weeks after surgical decompression and compared to 6 control dogs. MRI scans were performed preoperatively and 12 weeks after MFR was observed. DTI metrics were obtained at the lesion epicentre and one SC segment cranially and caudally. Variance analyses were performed to compare values between evaluated localizations in affected dogs and controls and between time points. Correlations between DTI metrics and clinical scores at follow-up examinations were assessed., Results: Before surgery, FA values at epicentres were higher than caudally (p = 0.0014) and control values (p = 0.0097); ADC values were lower in the epicentre compared to control values (p = 0.0035) and perilesional (p = 0.0448 cranially and p = 0.0433 caudally). In follow-up examinations, no significant differences could be found between DTI values from dogs showing MFR and control dogs. Lower ADC values at epicentres correlated with neurological deficits at follow-up examinations (r = - 0.705; p = 0.0023)., Conclusions: Findings suggest that a tendency to the return of DTI values to the physiological situation after surgical decompression accompanies MFR after SCI in paraplegic dogs. DTI may represent a useful and objective clinical tool for follow-up studies examining in vivo SC recovery in treatment studies.

Study Design: Prospective cross-sectional cohort study., Objectives: The canine spontaneous model of spinal cord injury (SCI) is as an important pre-clinical platform as it recapitulates key facets of human injury in a naturally occurring context. The establishment of an observational canine SCI registry constitutes a key step in performing epidemiologic studies and assessing the impact of therapeutic strategies to enhance translational research. Further, accumulating information on dogs with SCI may contribute to current "big data" approaches to enhance understanding of the disease using heterogeneous multi-institutional, multi-species datasets from both pre-clinical and human studies., Setting: Multiple veterinary academic institutions across the United States and Europe., Methods: Common data elements recommended for experimental and human SCI studies were reviewed and adapted for use in a web-based registry, to which all dogs presenting to member veterinary tertiary care facilities were prospectively entered over ~1 year., Results: Analysis of data accumulated during the first year of the registry suggests that 16% of dogs with SCI present with severe, sensorimotor-complete injury and that 15% of cases are seen by a tertiary care facility within 8 h of injury. Similar to the human SCI population, 34% were either overweight or obese., Conclusions: Severity of injury and timing of presentation suggests that neuroprotective studies using the canine clinical model could be conducted efficiently using a multi-institutional approach. Additionally, pet dogs with SCI experience similar comorbidities to people with SCI, in particular obesity, and could serve as an important model to evaluate the effects of this condition.

Study Design: Prospective observational-analytical study., Objectives: Description of diffusion tensor imaging (DTI) metrics obtained from the spinal cord (SC) of dogs with severe acute or chronic spontaneous, non-experimentally induced spinal cord injury (SCI) and correlation of DTI values with lesion extent of SCI measured in T2-weighted (T2W) magnetic resonance imaging sequences., Setting: Hannover, Germany., Methods: Forty-seven paraplegic dogs, 32 with acute and 15 with chronic SCI, and 6 disease controls were included. T2W and DTI sequences of the thoracolumbar spinal cord were performed. Values of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were obtained from the epicentre of the lesion and one SC segment cranially and caudally and compared between groups. Pearson's correlation coefficient was calculated between DTI and T2W metrics., Results: During acute SCI, FA values were increased (P=0.0065) and ADC values were decreased (P=0.0099) at epicentres compared to disease controls. FA values obtained from dogs with chronic SCI were lower (P<0.0001 epicentres and caudally; P=0.0002 cranially) and ADC showed no differences compared to disease control values. Dogs with chronic SCI revealed lower FA and higher ADC compared to dogs with acute SCI (P<0.0001 for both values at all localisations). FA values from epicentre and cranially to the lesion during chronic SCI correlated with extent of lesion (r=0.5517; P=0.0052 epicentres and r=0.6810; P=0.0408 cranially)., Conclusion: Using DTI, differences between acute and chronic stages of spontaneous canine SCI were detected and correlations between T2W and DTI sequences were found in chronic SCI, supporting canine SCI as a useful large animal model.

Objectives: Post-traumatic intramedullary myelopathies and cavitations are well described lesions following spinal cord injury (SCI) in humans and have been described in histopathological evaluations in dogs. Human intramedullary myelopathies/cavitations are associated with severe initial SCI and deterioration of clinical signs. Canine intervertebral disc extrusions share similarities with SCI in humans. In this descriptive study, magnetic resonance imaging (MRI) findings in spinal cords of dogs suffering from chronic post-traumatic myelopathies, including cavitations, are elucidated. An additional aim of the study was to compare diagnostic imaging and histopathological findings and identify similarities between human and canine chronic post-traumatic spinal cord lesions., Methods: Thirty-seven dogs with thoracolumbar SCI and one or more 3Tesla MRI investigations more than 3 weeks after SCI were included. Extent of intramedullary lesions and particularly cavitations were evaluated and measured in sagittal and transverse MRI planes. These data were compared with clinical data., Results: A total of 91.9% of study patients developed chronic intramedullary lesions, and 86.5% developed intramedullary cavitations. Paraplegia without deep pain perception at initial examination was significantly associated with longer chronic myelopathies/cavitations (P = 0.002/P = 0.008), and with larger maximal cross-sectional area (mCSA) of the lesions (P = 0.041/0.005). In addition, a non-ambulatory status after decompressive surgery was also associated with the development of longer intramedullary lesions/cavitations (P<0.001) and larger lesion mCSA (P<0.001/P = 0.012). All dogs with negative outcome developed myelopathies/cavitations. In the group of 21 dogs with positive outcome, 3 did not develop any myelopathies, and 5 did not develop cavitations., Conclusions: Development of chronic intramedullary lesions/cavitations are common findings in canine SCI. Extensive chronic intramedullary lesions/cavitations reflect a severe initial SCI and negative clinical outcome. This supports the hypothesis that chronic spinal cord changes following SCI in humans share similarities with canine chronic spinal cord changes after spontaneous intervertebral disc extrusion.

Translation of therapeutic interventions for spinal cord injury (SCI) from laboratory to clinic has been historically challenging, highlighting the need for robust models of injury that more closely mirror the human condition. The high prevalence of acute, naturally occurring SCI in pet dogs provides a unique opportunity to evaluate expeditiously promising interventions in a population of animals that receive diagnoses and treatment clinically in a manner similar to persons with SCI, while adhering to National Institutes of Health guidelines for scientific rigor and transparent reporting. In addition, pet dogs with chronic paralysis are often maintained long-term by their owners, offering a similarly unique population for study of chronic SCI. Despite this, only a small number of studies have used the clinical dog model of SCI. The Canine Spinal Cord Injury Consortium (CANSORT-SCI) was recently established by a group of veterinarians and basic science researchers to promote the value of the canine clinical model of SCI. The CANSORT-SCI group held an inaugural meeting November 20 and 21, 2015 to evaluate opportunities and challenges to the use of pet dogs in SCI research. Key challenges identified included lack of familiarity with the model among nonveterinary scientists and questions about how and where in the translational process the canine clinical model would be most valuable. In light of these, we review the natural history, outcome, and available assessment tools associated with canine clinical SCI with emphasis on their relevance to human SCI and the translational process.

Intervertebral disc herniation (IVDH) is a common cause of spinal cord injury (SCI) in dogs. Microtubule-associated protein tau derives predominantly from neurons and axons, making it a potential marker of neuronal injury. A retrospective study, including 51 dogs with thoracolumbar or cervical IVDH and 12 clinically normal dogs, was designed to describe associations between cerebrospinal fluid (CSF) tau concentration, degree of neurological signs and motor functional recovery in dogs with IVDH. Signalment, degree of neurological dysfunction and outcome were recorded. Cisternal CSF tau values were determined by ELISA. Associations between CSF tau concentration and various clinical parameters were evaluated. Receiver-operating characteristics curve (ROC) analyses were performed to assess the validity of protein tau measurements. CSF tau concentrations were significantly higher in dogs showing plegia (median, 79.9 pg/mL; range, 0-778.7 pg/mL; P=0.016) compared to healthy dogs and dogs with paresis (median, 30.1 pg/mL; range, 0-193.1 pg/mL; P=0.025). Plegic dogs that improved by one neurological grade within 1 week had significantly lower tau protein levels compared to plegic dogs that needed more time for recovery or did not show an improvement (P=0.008). A CSF tau concentration >41.3 pg/mL had a sensitivity of 86% and specificity of 83% to predict an unsuccessful outcome in plegic dogs based on ROC analysis (area under the curve, 0.887; P=0.007, 95% confidence interval [CI] 0.717-1.057). CSF protein tau levels are positively associated with the severity of spinal cord damage and may serve as a prognostic indicator in dogs with IVDH., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Spinal cord injury (SCI) represents a devastating central nervous system disease that still lacks sufficient therapies. Here, dogs are increasingly recognized as a preclinical animal model for the development of future therapies. The aim of this study was a detailed characterization of axonopathy in canine intervertebral disc disease, which produces a mixed contusive and compressive injury and functions as a spontaneous translational animal model for human SCI. The results revealed an early occurrence of ultrastructurally distinct axonal swelling. Immunohistochemically, enhanced axonal expression of β-amyloid precursor protein, non-phosphorylated neurofilament (n-NF) and growth-associated protein-43 was detected in the epicenter during acute canine SCI. Indicative of a progressive axonopathy, these changes showed a cranial and caudally accentuated spatial progression in the subacute disease phase. In canine spinal cord slice cultures, immunoreactivity of axons was confined to n-NF. Real-time quantitative polymerase chain reaction of naturally traumatized tissue and slice cultures revealed a temporally distinct dysregulation of the matrix metalloproteinases (MMP)-2 and MMP-9 with a dominating expression of the latter. Contrasting to early axonopathy, diminished myelin basic protein immunoreactivity and phagocytosis were delayed. The results present a basis for assessing new therapies in the canine animal model for translational research that might allow partial extrapolation to human SCI., (© 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.)

Spinal cord injury (SCI) in dogs is a well recognized animal model to study pathogenesis and treatment modalities of the debilitating human disease. To define the contributing role of microglial cell activation to the secondary wave following SCI, microglia from 15 dogs with SCI confirmed by imaging, gross, and histopathological examination were isolated and characterized in terms of morphology, immunophenotype, and function ex vivo by flow cytometry, allowing single cell analysis. The results were compared to region-specific findings obtained from healthy control dogs. Light microscopy revealed a significant enhancement of myelinophagia within the traumatized spinal cord of dogs who had had SCI for ≥5 days. Immunophenotypical characterization revealed increased expression of B7-1, B7-2, MHC II, CD1c, ICAM 1, CD14, CD44, and CD45 emphasizing the enhanced function of microglia as co-stimulators of T cells, in leukocyte adhesion and aggregation, and for lipid or glycolipid presentation. In addition, phagocytosis and reactive oxygen species (ROS) generation were significantly increased in dogs with spinal cord trauma. Regional differences within the spinal cord were observed by demonstrating disparities in microglial immunophenotypes in the traumatized cervical compared to the thoracolumbar spinal cord. In contrast to histopathology, microglia activation analyzed on a single cell basis did not depend upon the time span following SCI.

Better understanding of the pathogenesis of spinal cord injury (SCI) is needed for the development of new therapeutic strategies. Spinal cord injury has been investigated in various rodent models, but extrapolation to humans requires the use of a large animal model that more closely mimics human SCI. Dogs frequently develop spontaneous SCI with features that bear a striking resemblance to the human counterpart. We investigated the temporal course of the immune response during naturally occurring canine SCI and in organotypic canine spinal cord slice cultures that are devoid of peripheral immune cells. By immunohistochemistry, the inflammatory response in subacute canine SCI was largely restricted to resident immune cells as demonstrated by activation of major histocompatibility complex class II-expressing microglia/macrophages. By quantitative polymerase chain reaction, there was parallel upregulation of proinflammatory cytokine gene expression (i.e. of interleukin 6 [IL-6] and IL-8 with a trend toward upregulation of tumor necrosis factor) in acute canine SCI. Expression of neuroprotective cytokines (e.g. IL-10) remained unchanged, and transforming growth factor β upregulation was delayed. In organotypic spinal cord slices, there was similar activation of major histocompatibility complex class II-positive microglia and prolonged upregulation of inflammatory cytokines, indicating that resident rather than infiltrating cells play major roles in the postinjury immune response. Thus, canine SCI represents a bridge between rodent models and human SCI that may be relevant for clinical and preclinical treatment studies.