Cyclooxygenase-2 inhibitors differentially attenuate pentylenetetrazol-induced seizures and increase of pro- and anti-inflammatory cytokine levels in the cerebral cortex and hippocampus of mice

Temp, Fernanda R.; Marafiga, Joseane Righes; Milanesi, Laura Hautrive; Duarte, Thiago; Rambo, Leonardo Magno; Pillat, Micheli Mainardi; Mello, Carlos Fernando

doi:10.1016/j.ejphar.2017.05.013

Cited by 38 publications

(18 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…19,29 We hypothesize that CXB, however, carries out its effect via inhibition of pro-inflammatory cytokines, as well as inhibition of white blood cells and inflammatory cell recruitment early in the post-injury period. 30 Rabbits treated with CXB-loaded collagen membranes (group 3) did demonstrate decreased density of fibrous lesions, as well as reduced myofibroblast presence when compared to the vehicle membrane group (group 2). These data will require further investigation at earlier time points to demonstrate if this method of pharmacologic inhibition is able to decrease the density of myofibroblasts and fibrous tissue overall.…”

Section: Histopathology Datamentioning

confidence: 87%

Reduction of arthrofibrosis utilizing a collagen membrane drug‐eluting scaffold with celecoxib and subcutaneous injections with ketotifen

Limberg

Tibbo

Salib

et al. 2020

Journal Orthopaedic Research

View full text Add to dashboard Cite

The dense formation of abnormal scar tissue after total knee arthroplasty results in arthrofibrosis, an unfortunate sequela of inflammation. The purpose of this study was to use a validated rabbit model to assess the effects on surgically-induced knee joint contractures of two combined pharmacological interventions: celecoxib (CXB) loaded on an implanted collagen membrane, and subcutaneously (SQ) injected ketotifen. Thirty rabbits were randomly divided into five groups. The first group received no intervention after the index surgery. The remaining four groups underwent intra-articular implantation of collagen membranes loaded with or without CXB at the time of the index surgery; two of which were also treated with SQ ketotifen. Biomechanical joint contracture data were collected at 8, 10, 16, and 24 weeks. At the time of necropsy (24 weeks), posterior capsule tissue was collected for messenger RNA and histopathologic analyses. At 24 weeks, there was a statistically significant increase in passive extension among rabbits in all groups treated with CXB and/or ketotifen compared to those in the contracture control group. There was a statistically significant decrease in COL3A1, COL6A1, and ACTA2 gene expression in the treatment groups compared to the contracture control group (P < .001). Histopathologic data also demonstrated a trend towards decreased fibrous tissue density in the CXB membrane group compared to the vehicle membrane group. The present data suggest that intra-articular placement of a treated collagen membrane blunts the severity of contracture development in a rabbit model of arthrofibrosis, and that ketotifen and CXB may independently contribute to the prevention of arthrofibrosis. Statement of clinical significance: Current literature has demonstrated that arthrofibrosis may affect up to 5% of primary total knee arthroplasty patients. For that reason, novel pharmacologic prophylaxis and treatment modalities are critical to

show abstract

Section: Histopathology Datamentioning

confidence: 87%

Reduction of arthrofibrosis utilizing a collagen membrane drug‐eluting scaffold with celecoxib and subcutaneous injections with ketotifen

Limberg

Tibbo

Salib

et al. 2020

Journal Orthopaedic Research

View full text Add to dashboard Cite

show abstract

“…CXB is a cyclooxygenase inhibitor that selectively targets the COX‐2 enzyme, inhibiting the production of pro‐inflammatory cytokines (IL‐1β, IL‐6, IFN‐γ, TNF‐α) . This inhibition decreases the recruitment of white blood cells and other inflammatory cells and decreases sensitization in pain receptors .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of COX‐2 Pathway as a Potential Prophylaxis Against Arthrofibrogenesis in a Rabbit Model of Joint Contracture

Salib

Reina

Trousdale

et al. 2019

Journal Orthopaedic Research

View full text Add to dashboard Cite

Arthrofibrosis is a common complication following total knee arthroplasty caused by pathologic fibroblast activation and excessive collagen deposition around a synovial joint leading to debilitating loss of motion. Treatment options are limited because the pathologic mechanisms remain to be characterized. Dysregulation of the inflammatory cascade may lead to communication between myofibroblasts and immune cells triggering tissue metaplasia, and excessive collagen deposition described clinically as arthrofibrosis. We explored the novel use of celecoxib (selective cyclooxygenase-2 [COX-2] inhibitor) to disrupt the downstream effects of the post-traumatic inflammatory cascade and inhibit scar tissue formation in a validated rabbit model of arthrofibrosis combined with new parameters for quantifying the stiffness of the posterior capsule. Biomechanical and molecular analyses, of contracted rabbit knee posterior capsule tissue after COX-2 inhibition revealed increased maximal passive extension and down-regulation of collagen messenger RNA compared with controls. Histopathologic examination suggested a trend of decreased quantities of dense fibrous connective tissue with COX-2 inhibition. These data may suggest that inhibiting the inflammatory cascade could potentially reduce pathologic myofibroblast activation, thereby reducing scar tissue formation and increasing the range of motion in arthrofibrotic joints. Implementing a multi-modal pharmacologic approach may simultaneously target numerous cellular components contributing to the complex process of arthrofibrogenesis.

show abstract

“…Experimental data from rodent models confirmed that enhanced activation of inflammatory pathways can contribute to enhanced excitability and lowered thresholds in the epileptic brain [3][4][5]. Moreover, increased expression rates of various pro-inflammatory mediators have been demonstrated in brain tissue from rodent epilepsy models as well as human patients with epilepsy [1,[6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 78%

Molecular alterations of the TLR4-signaling cascade in canine epilepsy

et al. 2020

View full text Add to dashboard Cite

Background: Cumulating evidence from rodent models points to a pathophysiological role of inflammatory signaling in the epileptic brain with Toll-like receptor-4 signaling acting as one key factor. However, there is an apparent lack of information about expression alterations affecting this pathway in canine patients with epilepsy. Therefore, we have analyzed the expression pattern of Toll-like receptor 4 and its ligands in brain tissue of canine patients with structural or idiopathic epilepsy in comparison with tissue from laboratory dogs or from owner-kept dogs without neurological diseases. Results: The analysis revealed an overexpression of Toll-like receptor-4 in the CA3 region of dogs with structural epilepsy. Further analysis provided evidence for an upregulation of Toll-like receptor-4 ligands with high mobility group box-1 exhibiting increased expression levels in the CA1 region of dogs with idiopathic and structural epilepsy, and heat shock protein 70 exhibiting increased expression levels in the piriform lobe of dogs with idiopathic epilepsy. In further brain regions, receptor and ligand expression rates proved to be either in the control range or reduced below control levels. Conclusions: Our study reveals complex molecular alterations affecting the Toll-like receptor signaling cascade, which differ between epilepsy types and between brain regions. Taken together, the data indicate that multitargeting approaches modulating Toll-like receptor-4 signaling might be of interest for management of canine epilepsy. Further studies are recommended to explore respective molecular alterations in more detail in dogs with different etiologies and to confirm the role of the pro-inflammatory signaling cascade as a putative target.

show abstract

Cyclooxygenase-2 inhibitors differentially attenuate pentylenetetrazol-induced seizures and increase of pro- and anti-inflammatory cytokine levels in the cerebral cortex and hippocampus of mice

Cited by 38 publications

References 63 publications

Reduction of arthrofibrosis utilizing a collagen membrane drug‐eluting scaffold with celecoxib and subcutaneous injections with ketotifen

Reduction of arthrofibrosis utilizing a collagen membrane drug‐eluting scaffold with celecoxib and subcutaneous injections with ketotifen

Inhibition of COX‐2 Pathway as a Potential Prophylaxis Against Arthrofibrogenesis in a Rabbit Model of Joint Contracture

Molecular alterations of the TLR4-signaling cascade in canine epilepsy

Contact Info

Product

Resources

About