Prominent Microglial Activation in the Early Proinflammatory Immune Response in Naturally Occurring Canine Spinal Cord Injury

Spitzbarth, Ingo; Bock, Przemek J.; Haist, Verena; Stein, Veronika M.; Tipold, Andrea; Wewetzer, Konstantin; Baumgärtner, Wolfgang; Beineke, Andreas

doi:10.1097/nen.0b013e3182270f8e

Cited by 66 publications

(104 citation statements)

References 91 publications

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“…In a previous study that examined mRNA expression of cytokines in the spinal cord of dogs with IVDH-associated SCI, IL-8 was likewise found to be increased, compared to control dogs, especially in acute injury. 9 It should be noted that neutrophilic inflammation was not prevalent in animals in that study, which is in contrast to most other reports that have examined spinal cord or …”

Section: Discussioncontrasting

confidence: 52%

“…7 A small group of studies has demonstrated that inflammatory mechanisms may play a critical role in canine IVDH-associated SCI. [8][9][10][11] In particular, in acute canine SCI, resident microglial activation is prominent as is upregulation of matrix metalloproteinase 9, release of myelin basic protein, and overproduction of interleukin (IL)-6 and IL-8 messenger RNA (mRNA). [9][10][11][12] In order to further develop this model system, a broader understanding of inflammatory mechanisms after SCI is needed, particularly if pathways are to be targeted in preclinical trials.…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal Fluid Inflammatory Cytokines and Chemokines in Naturally Occurring Canine Spinal Cord Injury

Taylor

Welsh²,

Young³

et al. 2014

Journal of Neurotrauma

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Canine intervertebral disk herniation (IVDH) is a common, naturally occurring form of spinal cord injury (SCI) that is increasingly being used in pre-clinical evaluation of therapies. Although IVDH bears critical similarities to human SCI with respect to lesion morphology, imaging features, and post-SCI treatment, limited data are available concerning secondary injury mechanisms. Here, we characterized cerebrospinal fluid (CSF) cytokines, and chemokines in dogs with acute, surgically treated, thoracolumbar IVDH (n = 39) and healthy control dogs (n = 21) to investigate early inflammatory events after SCI. A bioplex system was used to measure interleukin (IL)-2, -6, -7, -8, -10, -15, and -18, granulocyte macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-c), keratinocyte chemoattractant (KC)-like protein, IFN-c-inducible protein-10, monocyte chemotactic protein 1 (MCP-1), and tumor necrosis factor alpha. Cytokine and chemokine concentrations in the CSF of healthy and SCI dogs were compared and, in SCI dogs, were correlated to the duration of SCI, behavioral measures of injury severity at the time of sampling, and neurological outcome 42 days post-SCI as determined by a validated ordinal score. IL-8 concentration was significantly higher in SCI cases than healthy controls ( p = 0.0013) and was negatively correlated with the duration of SCI ( p = 0.042). CSF MCP-1 and KC-like protein were positively correlated with CSF microprotein concentration in dogs with SCI ( p < 0.0001 and p = 0.004). CSF MCP-1 concentration was negatively associated with 42-day postinjury outcome ( p < 0.0001). Taken together, these data indicate that cytokines and chemokines present after SCI in humans and rodent models are associated with SCI pathogenesis in canine IVDH.

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Section: Discussioncontrasting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Inflammatory Cytokines and Chemokines in Naturally Occurring Canine Spinal Cord Injury

Taylor

Welsh²,

Young³

et al. 2014

Journal of Neurotrauma

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“…Lipopolysaccharides induce the expression of IL-6 in canine macrophages, such as DH82 cells (Fujimoto et al 2012), blood mononuclear cells and Kupffer cells in vitro (Hamano et al 2002;Shi et al 1995). Moreover, IL-6 expression is associated with inflammation (Spitzbarth et al 2011) and macrophage infiltration into inflamed tissues in dog (Klocke et al 2005). IFNγ expression is also a result of the activation of blood mononuclear cells in the dog (Panaro et al 2001) and increases the cytotoxic activity of canine alveolar macrophages in vitro (Kurzman et al 1999).…”

Section: Discussionmentioning

confidence: 99%

Adipose tissue macrophages in non-rodent mammals: a comparative study

et al. 2015

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The stromal vascular fraction (SVF) of adipose tissue in rodents and primates contains mesenchymal stem cells and immune cells. SVF cells have complex metabolic, immune and endocrine functions with biomedical impact. However, in other mammals, the amount of data on SVF stem cells is negligible and whether the SVF hosts immune cells is unknown. In this study, we show that the SVF is rich in immune cells, with a dominance of adipose tissue macrophages (ATMs) in cattle (Bos primigenius taurus), domestic goat (Capra aegagrus hircus), domestic sheep (Ovis aries), domestic cat (Felis catus) and domestic dog (Canis familiaris). ATMs of these species are granulated lysosome-rich cells with lamellipodial protrusions and express the lysosome markers acid phosphatase 5 (ACP-5) and Mac-3/Lamp-2. Using ACP-5 and Mac-3/Lamp-2 as markers, we additionally detected ATMs in other species, such as the domestic horse (Equus ferus caballus), wild boar (Sus scrofa) and red fox (Vulpes vulpes). Feline and canine ATMs also express the murine macrophage marker F4/80 antigen. In the lean condition, the alternative macrophage activation marker CD206 is expressed by feline and canine ATMs and arginase-1 by feline ATMs. Obesity is associated with interleukin-6 and interferon gamma expression and with overt tyrosine nitration in both feline and canine ATMs. This resembles the obesity-induced phenotype switch of murine and human ATMs. Thus, we show, for the first time, that the presence of ATMs is a general trait of mammals. The interaction between the adipose cells and SVF immune cells might be evolutionarily conserved among mammals.

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“…However, shortly after the primary injury, a complex and dynamic cascade of cellular processes including inflammation, edema, ischemia, reactive species liberation, excitotoxicity, and microglial and astrocytic activation occur 11, 12, 13, 14. This spectrum of responses is known as the “secondary injury,” and it occurs seconds to weeks after the primary injury 12, 15…”

mentioning

confidence: 99%

Comparison of Preoperative Quantitative Magnetic Resonance Imaging and Clinical Assessment of Deep Pain Perception as Prognostic Tools for Early Recovery of Motor Function in Paraplegic Dogs with Intervertebral Disk Herniations

Wang‐Leandro

Siedenburg

Hobert

et al. 2017

Veterinary Internal Medicne

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BackgroundPrognostic tools to predict early postoperative motor function recovery (MFR) after thoracolumbar intervertebral disk herniation (IVDH) in paraplegic dogs represent an opportunity to timely implement novel therapies that could shorten recovery times and diminish permanent neurological dysfunctions.HypothesisFractional anisotropy (FA) values obtained using diffusion tensor imaging have a higher prognostic value than a lesion extension ratio in T2‐weighted images (T2W‐LER) and clinical assessment of deep pain perception (DPP) for MFR.AnimalsThirty‐five paraplegic dogs with diagnosis of acute or subacute thoracolumbar IVDH.MethodsProspective, descriptive observational study. At admission, absence or presence of DPP, T2W‐LER, and FA values was evaluated. MFR was assessed within 4 weeks after decompressive surgery. Values of T2W‐LER and FA of dogs with and without MFR were compared using t‐tests. All 3 methods were evaluated for their sensitivity and specificity as a prognostic factor.ResultsNo differences were found between groups regarding T2W‐LER. FA values differed statistically when measured caudally of lesion epicenter being higher in dogs without MFR compared to dogs with MFR (P = .023). Logistic regression analysis revealed significance in FA values measured caudally of the lesion epicenter (P = .033, area under the curve = 0.72). Using a cutoff value of FA = 0.660, the technique had a sensitivity of 80% and a specificity of 55%. Evaluation of DPP had a sensitivity of 73.3% and specificity of 75% (P = .007).Conclusions and Clinical ImportanceEvaluation of DPP showed a similar sensitivity and a better specificity predicting early MFR than quantitative magnetic resonance imaging.

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Prominent Microglial Activation in the Early Proinflammatory Immune Response in Naturally Occurring Canine Spinal Cord Injury

Cited by 66 publications

References 91 publications

Cerebrospinal Fluid Inflammatory Cytokines and Chemokines in Naturally Occurring Canine Spinal Cord Injury

Cerebrospinal Fluid Inflammatory Cytokines and Chemokines in Naturally Occurring Canine Spinal Cord Injury

Adipose tissue macrophages in non-rodent mammals: a comparative study

Comparison of Preoperative Quantitative Magnetic Resonance Imaging and Clinical Assessment of Deep Pain Perception as Prognostic Tools for Early Recovery of Motor Function in Paraplegic Dogs with Intervertebral Disk Herniations

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