Remote inflammatory response in liver is dependent on the segmental level of spinal cord injury

Fleming, Jennifer C.; Bailey, Christopher S.; Hundt, H. K. L.; Gurr, Kevin R.; Bailey, Stewart I.; Cepinskas, Gediminas; Lawendy, Abdel-Rahman; Badhwar, Amit

doi:10.1097/ta.0b013e31824d68bd

Cited by 29 publications

(23 citation statements)

References 37 publications

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“…SCI at cervical and high thoracic levels is known to trigger a severe systemic inflammatory response 20 , but the role of inflammation in complete spinal transection at the mid-thoracic-level and the secondary voiding dysfunction was not investigated so far. An earlier study on SCI patients 18 identified IL-6, CXCL-1, and CCL2 as potential serum biomarkers for SCI.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous Recovery of Reflex Voiding Following Spinal Cord Injury Mediated by Anti-inflammatory and Neuroprotective Factors

Tyagi

Kadekawa

Kashyap

et al. 2016

Urology

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Objective To investigate the time dependent changes in expression of cytokines that characterizes the spontaneous recovery of reflex voiding after spinal cord injury (SCI). SCI is known to reorganize the neural circuitry of micturition reflex after injury. Methods Under isoflurane anesthesia, spinal cord of 18 adult female Sprague-Dawley rats was completely transected at the Th9/10 level. Awake cystometry was performed on controls and 6 SCI animals at each time point of 4, 8 and 12 weeks and bladder was then harvested for analysis of 29 proteins Millipore kit or ELISA. Prophylactic dose of ampicillin 100mg/kg was administered periodically to all SCI animals. Results Spontaneous recovery of voiding after SCI at 12 weeks was evident from increased intercontractile interval and voiding efficiency during cystometry. Expression of pro-inflammatory interleukins (IL-1α and IL-1β, IL-2 IL-5, IL-6, IL-18, TNF-α) and CXC chemokines (CXCL1, CXCL2, CXCL10), CX3CL1 and CCL2 showed significant elevation at 4 and 8 weeks with slight decrease at 12 weeks. In contrast, expression of anti-inflammatory interleukin IL-10 and neuroprotective factors, BDNF,CXCL-5 and Leptin was elevated at 8 and 12 weeks (p<0.05). In contrast, expression of CCL3, CCL5 and growth factors VEGF, NGF, EGF, G-CSF, GM-CSF did not show any significant temporal change after SCI. Conclusions Spontaneous recovery of reflex voiding at 12 weeks was marked by increased endogenous expression of anti-inflammatory cytokine IL-10 and neuroprotective factors BDNF, CXCL-5 and leptin, which suggests that pharmacological suppression of inflammation, can hasten the emergence of reflex voiding after SCI.

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Section: Discussionmentioning

confidence: 99%

Spontaneous Recovery of Reflex Voiding Following Spinal Cord Injury Mediated by Anti-inflammatory and Neuroprotective Factors

Tyagi

Kadekawa

Kashyap

et al. 2016

Urology

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“…[1][2][3][4][5] Data in Figure 1 show that activated Kupffer cells, the resident hepatic macrophages, persist at and beyond 1 dpi in liver. Indeed, hepatic CD68 mRNA increased > 100-fold by 1 dpi and remained at that level for at least 21 dpi (Fig.…”

Section: Thoracic Sci Induces Robust Liver Inflammation and Lipid Accmentioning

confidence: 99%

“…SCI initiates a systemic inflammatory response defined by rapid elevation of chemokines and leukocytes in the circulation, lungs, kidneys, and liver, which evokes local tissue pathology such as edema and bleeding. [1][2][3][4][5][6] This systemic response in turn likely contributes to acute and possibly chronic dysfunction in patients with SCI.…”

Section: Introductionmentioning

confidence: 99%

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Spinal Cord Injury Causes Chronic Liver Pathology in Rats

Sauerbeck

Laws

Bandaru

et al. 2015

Journal of Neurotrauma

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Traumatic spinal cord injury (SCI) causes major disruption to peripheral organ innervation and regulation. Relatively little work has investigated these post-SCI systemic changes, however, despite considerable evidence that multiple organ system dysfunction contributes to chronic impairments in health. Because metabolic dysfunction is common after SCI and the liver is a pivotal site for metabolic homeostasis, we sought to determine if liver pathology occurs as a result of SCI in a rat spinal contusion model. Histologic evidence showed excess lipid accumulation in the liver for at least 21 days post-injury after cervical or midthoracic SCI. Lipidomic analysis revealed an acute increase in hepatic ceramides as well as chronically elevated lactosylceramide. Post-SCI hepatic changes also included increased proinflammatory gene expression, including interleukin (IL)-1a, IL-1b, chemokine ligand-2, and tumor necrosis factor-a mRNA. These were coincident with increased CD68 + macrophages in the liver through 21 days post-injury. Serum alanine transaminase, used clinically to detect liver damage, was significantly increased at 21 days post-injury, suggesting that early metabolic and inflammatory damage preceded overt liver pathology. Surprisingly, liver inflammation was even detected after lumbar SCI. Collectively, these results suggest that SCI produces chronic liver injury with symptoms strikingly similar to those of nonalcoholic steatohepatitis (fatty liver disease). These clinically significant hepatic changes after SCI are known to contribute to systemic inflammation, cardiovascular disease, and metabolic syndrome, all of which are more prevalent in persons with SCI. Targeting acute and prolonged hepatic pathology may improve recovery and reduce long-term complications after SCI.

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“…It has been previously demonstrated that SCI causes local and systemic inflammatory responses which are associated with the production of free radicals (18)(19)(20). Free radical-induced lipid peroxidation is one of the mechanisms of the secondary spinal cord injury which result in an autodestructive phenomenon of spinal cord (21).…”

Section: Discussionmentioning

confidence: 99%

Tadalafil attenuates spinal cord injury induced oxidative organ damage in rats

Şener¹

2014

mpj

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Spinal cord injury (SCI) has been shown to cause systemic inflammatory response syndrome (SIRS) which damages multiple organs due to an influx of inflammatory cells from the circulation. In this study, we evaluated the effect of tadalafil, a phoshodiesterase inhibitor, against spinal cord, kidney and bladder damage in experimental animal model of spinal cord injury. Male Wistar albino rats were divided into sham-operated control, and either vehicle or tadalafil-treated SCI groups. In order to induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10, was used. Injured animals were given either 10 mg/kg tadalafil or vehicle 15 minutes post injury and repeated daily for seven days. After decapitation spinal cord, kidney and bladder tissue samples were obtained to examine oxidative tissue injury; malondialdehyde (MDA) and glutathione (GSH) levels, and superoxide dismutase (SOD), myeloperoxidase (MPO) and caspase-3 activities. Tissues were also examined histologically. In the injured animals, MDA levels MPO and caspase-3 activities in tissues were found significantly increased while tadalafil treatment reversed these increases. On the other hand SCI-induced decreases in GSH levels and SOD activities were also reversed with tadalafil treatment. According to the results, tadalafil exerts beneficial effects against SCI-induced oxidative damage in spinal cord and also in remote organs such as kidney and bladder tissues through its antiinflammatory and antioxidant effects.

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Remote inflammatory response in liver is dependent on the segmental level of spinal cord injury

Abstract: Our findings indicate that traumatic SCI triggers an acute SIR that contributes to hepatocellular injury. SCI-induced remote injury/dysfunction to the liver appears to be transient and is more robust after an upper thoracic SCI compared with a lower thoracic SCI.

Cited by 29 publications

References 37 publications

Spontaneous Recovery of Reflex Voiding Following Spinal Cord Injury Mediated by Anti-inflammatory and Neuroprotective Factors

Spontaneous Recovery of Reflex Voiding Following Spinal Cord Injury Mediated by Anti-inflammatory and Neuroprotective Factors

Spinal Cord Injury Causes Chronic Liver Pathology in Rats

Tadalafil attenuates spinal cord injury induced oxidative organ damage in rats

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