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The lack of therapeutics that prevent the development of epilepsy, improve disease prognosis or overcome drug resistance represents an unmet clinical need in veterinary as well as in human medicine. Over the past decade, experimental studies and studies in human epilepsy patients have demonstrated that neuroinflammatory processes are involved in epilepsy development and play a key role in neuronal hyperexcitability that underlies seizure generation. Targeting neuroinflammatory signaling pathways may provide a basis for clinically relevant disease-modification strategies in general, and moreover, could open up new therapeutic avenues for human and veterinary patients with drug-resistant epilepsy. A sound understanding of the neuroinflammatory mechanisms underlying seizure pathogenesis in canine patients is therefore essential for mechanism-based discovery of selective epilepsy therapies that may enable the development of new disease-modifying treatments. In particular, subgroups of canine patients in urgent needs, e.g. dogs with drug-resistant epilepsy, might benefit from more intensive research in this area. Moreover, canine epilepsy shares remarkable similarities in etiology, disease manifestation, and disease progression with human epilepsy. Thus, canine epilepsy is discussed as a translational model for the human disease and epileptic dogs could provide a complementary species for the evaluation of antiepileptic and antiseizure drugs. This review reports key preclinical and clinical findings from experimental research and human medicine supporting the role of neuroinflammation in the pathogenesis of epilepsy. Moreover, the article provides an overview of the current state of knowledge regarding neuroinflammatory processes in canine epilepsy emphasizing the urgent need for further research in this specific field. It also highlights possible functional impact, translational potential and future perspectives of targeting specific inflammatory pathways as disease-modifying and multi-target treatment options for canine epilepsy.

In the current study the hypothesis should be proven that T1 weighted Fast Field Echo (FFE) sequence is a useful method to visualize intervertebral disc degeneration, respectively changes of the expected disc appearance. Medical records of 208 dogs were reviewed and images of 781 intervertebral discs were evaluated by two blinded examiners using a modified Pfirrmann classification system in two MRI sequences: FFE and Turbo-Spin-Echo T2-weighted sequence (T2W). The patients were allocated to three categories based on body conformation: (1) brachycephalic and chondrodystrophic breeds, (2) non-chondrodystrophic and non-brachycephalic breeds with a body weight of < 25 kg, and (3) non-chondrodystrophic and non-brachycephalic breeds with a body weight greater or equal 25 kg. In brachycephalic and chondrodystrophic dogs 340 intervertebral discs were evaluated, the majority of them presented a mild change of the normal disc structure, 53% in the FFE sequence and 41% in T2W images. High discrepancies were observed between mild and moderate degeneration: in the FFE-sequence 15% (n = 50) of the discs had signs of mild degeneration, whereas in T2W the same discs were graded as moderately degenerated. In non-chondrodystrophic and non-brachycephalic breeds under 25 kg body weight 320 intervertebral discs were assessed. In the FFE-sequence 52% (n = 166) of the intervertebral discs were judged as having a mild degeneration. In contrast, these same discs were graded as healthy discs (22%), mildly degenerated (33%), moderately degenerated (37%), and severely degenerated (8%) in T2W. In non-chondrodystrophic and non-brachycephalic breeds greater or equal 25 kg 121 intervertebral discs were assessed. The grading was equal in 43%, but differed in one grade (47%) and in two grades (10%) between the two sequences. In both sequences intervertebral disc herniations were equally well-diagnosed. The Kappa coefficient revealed a high discrepancy between the two MRI-sequences. In conclusion, FFE cannot replace the well-established T2W sequence for grading disc degeneration.

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.

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.

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

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.