The Impact of Nonsteroidal Anti-inflammatory Drugs on Inflammatory Response After Aneurysmal Subarachnoid Hemorrhage

Muroi, Carl; Hugelshofer, Michael; Seule, Martin; Keller, Emanuela

doi:10.1007/s12028-013-9930-2

Cited by 31 publications

(17 citation statements)

References 36 publications

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“…Regarding the systemic inflammatory response to the ANTI-inflammatory treatment, although Df is an NSAID extensively used as a COX inhibitor, its true mechanism of action remains to be highlighted [49]. In a clinical follow-up study of the systemic inflammatory response upon aneurysmal subarachnoid hemorrhage (SAH), the authors verified an inverse correlation between the amount of NSAID applied and the systemic pro-inflammatory parameters (IL-6 and C-Reactive Protein) in the acute phase (≤day 14) [50].…”

Section: Discussionmentioning

confidence: 96%

Modulation of the In Vivo Inflammatory Response by Pro- Versus Anti-Inflammatory Intervertebral Disc Treatments

Cunha

Teixeira

Ribeiro-Machado

et al. 2020

IJMS

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Inflammation is central in intervertebral disc (IVD) degeneration/regeneration mechanisms, and its balance is crucial to maintain tissue homeostasis. This work investigates the modulation of local and systemic inflammatory response associated with IVD degeneration/herniation by administration of PRO-versus ANTI-inflammatory treatments. Chitosan/poly-γ-glutamic acid nanocomplexes, known as pro-inflammatory (PRO), and soluble diclofenac, a non-steroidal anti-inflammatory drug (ANTI), were intradiscally administered in a rat IVD injury model, 24 h after lesion. Two weeks after administration, a reduction of disc height accompanied by hernia formation was observed. In the PRO-inflammatory treated group, IL-1β, IL-6 and COX-2 IVD gene expression were upregulated, and loss of nucleus pulposus (NP) structure and composition was observed. Systemically, lower T-cell frequency was observed in the lymph nodes (LN) and spleen (SP) of the PRO group, together with an increase in CD4+ T cells subset in the blood (BL) and LN. In contrast, the ANTI-group had higher proteoglycans/collagen ratio and collagen type 2 content in the NP, while an increase in the frequency of myeloid cells, M1 macrophages and activated macrophages (MHCII+) was observed at the systemic level. Overall, this study illustrates the dynamics of local and systemic inflammatory and immune cell responses associated with intradiscal therapies, which will contribute to designing more successful immunomodulatory treatments for IVD degeneration.Several in vivo models of IVD degeneration are described in the literature, with murine tail models of mechanical injury by needle puncture commonly used [4,5]. Depending on the needle size, the puncture may induce annulus fibrosus (AF) disruption while causing depressurization of the nucleus pulposus (NP) [6,7]. Needle calibers, varying between 16 to 22 G, often lead to significant pressure failure, decreased cell viability, increased expression of pro-inflammatory/degenerative factors and alterations in extracellular matrix (ECM) composition in IVDs from both large (e.g., bovine [8]) and small animals (e.g., rabbit [9] and rat [10]), resembling human IVD degeneration. Our group has previously established and validated an IVD herniation/degeneration model of rat caudal needle puncture, using a 21 G needle [10,11], in which IVD herniation and infiltration of macrophages were observed [10]. This model is relatively simple to manipulate and presents cost-effectiveness [12]. Moreover, it allows the study of local and systemic immune response, crucial in human IVD degeneration and difficult to analyze in vitro or ex vivo [13]. Only a few studies, mainly in bone, address the dialogue/interplay between local/systemic immune responses and how this can be linked with tissue remodeling [14,15]. Despite this, it is important to consider the limitations of small animal models of IVD degeneration when compared to humans, such as differences in spine biomechanics, IVD size and cellular composition, which may be critical for clinical trans...

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Section: Discussionmentioning

confidence: 96%

Modulation of the In Vivo Inflammatory Response by Pro- Versus Anti-Inflammatory Intervertebral Disc Treatments

Cunha

Teixeira

Ribeiro-Machado

et al. 2020

IJMS

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“…Another potential treatment target in the early phase after aSAH is to suppress neuroinflammation by the application of systemic anti-inflammatory drugs. Potential benefits in patients with SAH have been postulated [ 27 - 29 ] and are furthermore supported by the improvement of cerebral edema and decreasing neuronal cell apoptosis in experimental SAH models [ 30 ]. With the limitation of associated hemodynamic side effects [ 31 ] when applied as a rapid infusion, a continuous low-dose infusion may be considered [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Early brain injury after aneurysmal subarachnoid hemorrhage: a multimodal neuromonitoring study

et al. 2015

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IntroductionThere is a substantial amount of evidence from animal models that early brain injury (EBI) may play an important role for secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Cerebral microdialysis (CMD) allows online measurement of brain metabolites, including the pro-inflammatory cytokine interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9), which is indicative for disruption of the blood-brain barrier.MethodsTwenty-six consecutive poor-grade aSAH patients with multimodal neuromonitoring were analyzed for brain hemodynamic and metabolic changes, including CMD-IL-6 and CMD-MMP-9 levels. Statistical analysis was performed by using a generalized estimating equation with an autoregressive function.ResultsThe baseline cerebral metabolic profile revealed brain metabolic distress and an excitatory response which improved over the following 5 days (P <0.001). Brain tissue hypoxia (brain tissue oxygen tension of less than 20 mm Hg) was common (more than 60% of patients) in the first 24 hours of neuromonitoring and improved thereafter (P <0.05). Baseline CMD-IL-6 and CMD-MMP-9 levels were elevated in all patients (median = 4,059 pg/mL, interquartile range (IQR) = 1,316 to 12,456 pg/mL and median = 851 pg/mL, IQR = 98 to 25,860 pg/mL) and significantly decreased over days (P <0.05). A higher pro-inflammatory response was associated with the development of delayed cerebral ischemia (P = 0.04), whereas admission disease severity and early brain tissue hypoxia were associated with higher CMD-MMP-9 levels (P <0.03). Brain metabolic distress and increased IL-6 levels were associated with poor functional outcome (modified Rankin Scale of more than 3, P ≤0.01). All models were adjusted for probe location, aneurysm securing procedure, and disease severity as appropriate.ConclusionsMultimodal neuromonitoring techniques allow insight into pathophysiologic changes in the early phase after aSAH. The results may be used as endpoints for future interventions targeting EBI in poor-grade aSAH patients.

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“…The neuroinflammatory response in EBI after SAH has been identified in both clinical and experimental studies141516. Accordingly, anti-inflammatory intervention is a novel promising area of research for SAH treatment11.…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Sequencing and Co-Expression Network Analysis of lncRNAs and mRNAs in Early Brain Injury Following Experimental Subarachnoid Haemorrhage

Peng

Tian

et al. 2017

Sci Rep

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Subarachnoid haemorrhage (SAH) is a fatal neurovascular disease following cerebral aneurysm rupture with high morbidity and mortality rates. Long non-coding RNAs (lncRNAs) are a type of mammalian genome transcript, are abundantly expressed in the brain and are involved in many nervous system diseases. However, little is currently known regarding the influence of lncRNAs in early brain injury (EBI) after SAH. This study analysed the expression profiles of lncRNAs and mRNAs in SAH brain tissues of mice using high-throughput sequencing. The results showed a remarkable difference in lncRNA and mRNA transcripts between SAH and control brains. Approximately 617 lncRNA transcripts and 441 mRNA transcripts were aberrantly expressed at 24 hours after SAH. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the differentially expressed mRNAs were mostly involved in inflammation. Based on the lncRNA/mRNA co-expression network, knockdown of fantom3_F730004F19 reduced the mRNA and protein levels of CD14 and toll-like receptor 4 (TLR4) and attenuated inflammation in BV-2 microglia cells. These results indicate that lncRNA fantom3_F730004F19 may be associated with microglia induced inflammation via the TLR signaling pathway in EBI following SAH. LncRNA represent a potential therapeutic target for the prognosis, diagnosis, and treatment of SAH.

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The Impact of Nonsteroidal Anti-inflammatory Drugs on Inflammatory Response After Aneurysmal Subarachnoid Hemorrhage

Cited by 31 publications

References 36 publications

Modulation of the In Vivo Inflammatory Response by Pro- Versus Anti-Inflammatory Intervertebral Disc Treatments

Modulation of the In Vivo Inflammatory Response by Pro- Versus Anti-Inflammatory Intervertebral Disc Treatments

Early brain injury after aneurysmal subarachnoid hemorrhage: a multimodal neuromonitoring study

High-Throughput Sequencing and Co-Expression Network Analysis of lncRNAs and mRNAs in Early Brain Injury Following Experimental Subarachnoid Haemorrhage

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