Inflammatory markers assessment in an animal model of intracranial hypertension: a randomized trial

Abstract Background Intracranial hypertension (ICH) is a common final pathway of most neurosurgical pathologies and leads to poor prognosis if not detected and treated properly. Inflammatory markers have been assessed in clinical scenarios of neurological injuries, in which systemic and brain tissue aggressions may introduce bias. There is a lack of studies under controlled settings to isolate the ICH effect on inflammation. This study aims to evaluate the effects of ICH on the serum concentration of cytokines as biomarkers of neuroinflammation in an experimental model which isolates ICH from potential confounding variables. Methods An established model of ICH using an intracerebral pediatric bladder catheter and a multisensor intraparenchymal catheter was used in adult pigs (Sus domesticus). The animals were randomly allocated to 2 groups based on the catheter balloon volume used to simulate the ICP increase (4 ml or 7 ml). Cytokines were measured in 4 timepoints during the experiment: (1) 15 min before balloon insufflation; (2) 5 min after insufflation; (3) 125 min after insufflation; (4) 60 min after deflation. The following cytokines were measured IL-1α; IL-1β; IL–1ra; IL-2; IL-4; IL-6; IL-8; IL-10; IL-12; IL-18; TNFα. Generalized estimating equations were modeled to compare the ICP and cytokines values between the groups along the experiment. The study sample size was powered to detect interactions between the groups and the study moments with an effect size (f) of at least 0.3. The ARRIVE checklist was followed. Results A total of 20 animals were studied (10 in each group, 4 ml or 7 ml balloon volume insufflation). The animal model was successful in increasing the ICP along the moments of the experiment (p < 0,001) and in creating an ICP gradient between the groups (p = 0,004). The interaction term (moment × group) was also significant (p < 0,001). There was a significant association between ICP elevation and most cytokines variation. The cytokines IL-1α, IL-1β, IL1-ra, IL-6, IL-12, and IL-18 increased, whereas IL-2, IL-4, and TNF-α decreased. IL-10 did not vary significantly in response to the ICP elevation. Conclusion The serum concentration of cytokines varied in response to intracranial hypertension. The study demonstrated the specific changes in each cytokine after intracranial hypertension and provides key information to guide neuroinflammation clinical research. The proposed experiment was successful as an animal model to the study of neuroinflammation biomarkers

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Preconditioning with L-Ala-Gln reduces the expression of inflammatory markers (TNF-α, NF-κB, IL-6 and HO-1) in an injury animal model of cerebrovascular ischemia in Meriones unguiculatus (gerbils)

Acta Cirurgica Brasileira ◽

10.1590/s0102-865020200060000001 ◽

2020 ◽

Vol 35 (6) ◽

Author(s):

Leidelamar Rosário Alves de Oliveira ◽

Andréa de Oliveira Albuquerque ◽

Cícero Igor Simões Moura Silva ◽

Jussara Mathiele Silva ◽

Meyssa Quezado de Figueiredo Cavalcante Casadevall ◽

...

Keyword(s):

Animal Model ◽

Inflammatory Markers ◽

Meriones Unguiculatus ◽

Tnf Α

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Inflammatory Markers May Inform the Effects of Electroconvulsive Therapy on Cognition in Patients with Depression

Neuropsychobiology ◽

10.1159/000515931 ◽

2021 ◽

pp. 1-9

Author(s):

Jan-Baptist Belge ◽

Linda Van Diermen ◽

Bernard Sabbe ◽

Manuel Morrens ◽

Violette Coppens ◽

...

Keyword(s):

Episodic Memory ◽

Cognitive Functioning ◽

Electroconvulsive Therapy ◽

Inflammatory Markers ◽

Verbal Learning ◽

Potential Biomarker ◽

Tnf Α ◽

Autobiographic Memory ◽

Learning Test ◽

Verbal Episodic Memory

Introduction: The neurobiological mechanisms underlying the acute cognitive effects of electroconvulsive therapy (ECT) remain poorly understood. Prior research has shown that proinflammatory cytokines such as IL-6, TNF-α, IL1-β, and IL-10 may interfere with cognitive functioning. Interestingly, immunomodulation is one of the proposed modes of action of ECT. This study investigates whether changes of peripheral levels of IL-6, TNF-α, IL1-β, and IL-10 are related to changes in cognitive functioning following ECT. Methods: In the week before and 1 week after an acute course of ECT, 62 patients suffering from depression underwent a neuropsychological evaluation to assess their processing speed using the Symbol Digit Substitution Test (SDST), verbal episodic memory using the Hopkins Verbal Learning Test-Revised (HVLT-R), and their retrospective autobiographic memory using the Autobiographical Memory Interview (AMI) with the peripheral inflammatory markers being measured at the same 2 time points. Results: Patients improved drastically following ECT, while their main performance on both the HVLT-R and AMI declined and their SDST scores remained stable. The levels of IL-6 and IL1-β had both decreased, where the decrease in IL-6 was related to the decrease in HVLT-R scores. Higher baseline IL-10 levels were associated with a more limited decrease of the HVLT-R scores. Conclusion: Our findings tentatively suggest that the effects of ECT on verbal episodic memory may be related to the treatment’s immunomodulatory properties, most notably due to decreased IL-6 levels. Moreover, baseline IL-10 appears to be a potential biomarker to predict the effects of ECT on verbal episodic memory. Whilst compelling, the results of this study should be interpreted with caution as, due to its exploratory nature, no correction for multiple comparisons was made. Further, a replication in larger cohorts is warranted.

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Rat model of smoke inhalation-induced acute lung injury

BMJ Open Respiratory Research ◽

10.1136/bmjresp-2021-000879 ◽

2021 ◽

Vol 8 (1) ◽

pp. e000879

Author(s):

Premila Devi Leiphrakpam ◽

Hannah R Weber ◽

Tobi Ogun ◽

Keely L Buesing

Keyword(s):

Animal Model ◽

Acute Lung Injury ◽

Lung Injury ◽

Caspase 3 ◽

Small Animal ◽

Therapeutic Options ◽

Smoke Inhalation ◽

Small Animal Model ◽

Injury Score ◽

Confounding Variables

BackgroundAcute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a lethal disease with limited therapeutic options and an unacceptably high mortality rate. Understanding the complex pathophysiological processes involved in the development of ALI/ARDS is critical for developing novel therapeutic strategies. Smoke inhalation (SI) injury is the leading cause of morbidity and mortality in patients with burn-associated ALI/ARDS; however, to our knowledge few reliable, reproducible models are available for pure SI animal model to investigate therapeutic options for ALI/ARDS without the confounding variables introduced by cutaneous burn or other pathology.ObjectiveTo develop a small animal model of pure SI-induced ALI and to use this model for eventual testing of novel therapeutics for ALI.MethodsRats were exposed to smoke using a custom-made smoke generator. Peripheral oxygen saturation (SpO2), heart rate, arterial blood gas, and chest X-ray (CXR) were measured before and after SI. Wet/dry weight (W/D) ratio, lung injury score and immunohistochemical staining of cleaved caspase 3 were performed on harvested lung tissues of healthy and SI animals.ResultsThe current study demonstrates the induction of ALI in rats after SI as reflected by a significant, sustained decrease in SpO2 and the development of diffuse bilateral pulmonary infiltrates on CXR. Lung tissue of animals exposed to SI showed increased inflammation, oedema and apoptosis as reflected by the increase in W/D ratio, injury score and cleaved caspase 3 level of the harvested tissues compared with healthy animals.ConclusionWe have successfully developed a small animal model of pure SI-induced ALI. This model is offered to the scientific community as a reliable model of isolated pulmonary SI-induced injury without the confounding variables of cutaneous injury or other systemic pathology to be used for study of novel therapeutics or other investigation.

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In vitro evidence for the involvement of H2S pathway in the effect of clodronate during inflammatory response

Scientific Reports ◽

10.1038/s41598-021-94228-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rosangela Montanaro ◽

Alessio D’Addona ◽

Andrea Izzo ◽

Carlo Ruosi ◽

Vincenzo Brancaleone

Keyword(s):

Inflammatory Markers ◽

In Vitro Study ◽

Inos Expression ◽

Beneficial Effects ◽

Tnf Α ◽

Inflammatory State ◽

Anti Inflammatory ◽

Underlying Mechanisms ◽

Inflammatory Effect

AbstractClodronate is a bisphosphonate agent commonly used as anti-osteoporotic drug. Throughout its use, additional anti-inflammatory and analgesic properties have been reported, although the benefits described in the literature could not solely relate to their inhibition of bone resorption. Thus, the purpose of our in vitro study is to investigate whether there are underlying mechanisms explaining the anti-inflammatory effect of clodronate and possibly involving hydrogen sulphide (H2S). Immortalised fibroblast-like synoviocyte cells (K4IM) were cultured and treated with clodronate in presence of TNF-α. Clodronate significantly modulated iNOS expression elicited by TNF-α. Inflammatory markers induced by TNF-α, including IL-1, IL-6, MCP-1 and RANTES, were also suppressed following administration of clodronate. Furthermore, the reduction in enzymatic biosynthesis of CSE-derived H2S, together with the reduction in CSE expression associated with TNF-α treatment, was reverted by clodronate, thus rescuing endogenous H2S pathway activity. Clodronate displays antinflammatory properties through the modulation of H2S pathway and cytokines levels, thus assuring the control of the inflammatory state. Although further investigation is needed to stress out how clodronate exerts its control on H2S pathway, here we showed for the first the involvement of H2S in the additive beneficial effects observed following clodronate therapy.

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Effects of 12 Weeks of Exercise on Hepatic TNF-α and PPARα in an Animal Model of High-Fat Diet-Induced Nonalcoholic Steatohepatitis

Journal of Exercise Science & Fitness ◽

10.1016/s1728-869x(09)60003-4 ◽

2009 ◽

Vol 7 (1) ◽

pp. 18-23 ◽

Cited By ~ 3

Author(s):

Haifeng Zhang ◽

Yuxiu He ◽

Pak Kwong Chung ◽

Tom K. Tong ◽

Frank H. Fu ◽

...

Keyword(s):

Animal Model ◽

Nonalcoholic Steatohepatitis ◽

High Fat Diet ◽

High Fat ◽

Tnf Α

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Lycopene attenuates LPS-induced TNF-α secretion in macrophages and inflammatory markers in adipocytes exposed to macrophage-conditioned media

Molecular Nutrition & Food Research ◽

10.1002/mnfr.201100623 ◽

2012 ◽

Vol 56 (5) ◽

pp. 725-732 ◽

Cited By ~ 78

Author(s):

Julie Marcotorchino ◽

Beatrice Romier ◽

Erwan Gouranton ◽

Celine Riollet ◽

Beatrice Gleize ◽

...

Keyword(s):

Inflammatory Markers ◽

Conditioned Media ◽

Tnf Α

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Association of acylated ghrelin profiles with chronic inflammatory markers in overweight and obese postmenopausal women: a MONET study

Acta Endocrinologica ◽

10.1530/eje-07-0038 ◽

2007 ◽

Vol 157 (4) ◽

pp. 419-426 ◽

Cited By ~ 10

Author(s):

David H St-Pierre ◽

Jean-Philippe Bastard ◽

Lise Coderre ◽

Martin Brochu ◽

Antony D Karelis ◽

...

Keyword(s):

Postmenopausal Women ◽

Inflammatory Markers ◽

Area Under The Curve ◽

Blood Lipid ◽

Cross Sectional Study ◽

Acylated Ghrelin ◽

Euglycemic Hyperinsulinemic Clamp ◽

Cross Sectional ◽

Tnf Α ◽

Maximal Reduction

Objective: Recent reports have suggested that the existence of associations between hormonal dysregulation and chronic upregulation of inflammatory markers, which may cause obesity-related disturbances. Thus, we examined whether acylated ghrelin (AcylG) and total ghrelin (TotG) levels could be associated with the following inflammatory markers: C-reactive protein (CRP), tumor necrosis factor α (TNF-α), and soluble TNF receptor 1 (sTNF-R1). Design: Cross-sectional study consisting of 50 overweight and obese postmenopausal women. Methods: AcylG and TotG levels were assessed at 0, 60, 160, 170, and 180 min of the euglycemic/hyperinsulinemic clamp (EHC). We evaluated insulin sensitivity, body composition, and blood lipid profiles as well as fasting concentrations of CRP, TNF-α, and sTNF-R1. Results: In fasting conditions, sTNF-R1 was negatively correlated with AcylG (r = −0.48, P < 0.001) levels. In addition, AcylG/TotG was associated negatively with sTNF-R1 (r = −0.44, P = 0.002) and positively with TNF-α (r = 0.38, P = 0.009) values. During the EHC, TotG (at all time points) and AcylG (at 60 and 160 min) values were significantly decreased from fasting concentrations. AcylG maximal reduction and area under the curve (AUC) values were correlated to sTNF-R1 (r = −0.35, P = 0.02 and r = −0.34, P = 0.02, respectively). Meanwhile, the AcylG/TotG AUC ratio was associated negatively with sTNF-R1 (r = −0.29, P < 0.05) and positively with TNF-α (r = 0.36, P = 0.02). Following adjustments for total adiposity, sTNF-R1 remained correlated with fasting and maximal reduction AcylG values. Similarly, AcylG/TotG ratios remained significantly correlated with sTNF-R1 and TNF-α. Importantly, 23% of the variation in sTNF-R1 was independently predicted by fasting AcylG. Conclusion: These results are the first to suggest that both fasting and EHC-induced AcylG profiles are correlated with fasting values of sTNF-R1, a component of the TNF-α system. Thus, AcylG may act, at least in part, as one mediator of chronic inflammatory activity in human obesity.

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Experimental model of intracranial hypertension with continuous multiparametric monitoring in swine

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20130126 ◽

2013 ◽

Vol 71 (10) ◽

pp. 802-806 ◽

Cited By ~ 4

Author(s):

Almir Ferreira de Andrade ◽

Matheus Schmidt Soares ◽

Gustavo Cartaxo Patriota ◽

Alessandro Rodrigo Belon ◽

Wellingson Silva Paiva ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Animal Model ◽

Brain Injury ◽

Intracranial Pressure ◽

Intracranial Hypertension ◽

Severe Traumatic Brain Injury ◽

Transcranial Doppler ◽

Porcine Model ◽

Cerebral Oximetry ◽

Suitable Animal Model

Objective Intracranial hypertension (IH) develops in approximately 50% of all patients with severe traumatic brain injury (TBI). Therefore, it is very important to identify a suitable animal model to study and understand the pathophysiology of refractory IH to develop effective treatments. Methods We describe a new experimental porcine model designed to simulate expansive brain hematoma causing IH. Under anesthesia, IH was simulated with a balloon insufflation. The IH variables were measured with intracranial pressure (ICP) parenchymal monitoring, epidural, cerebral oximetry, and transcranial Doppler (TCD). Results None of the animals died during the experiment. The ICP epidural showed a slower rise compared with parenchymal ICP. We found a correlation between ICP and cerebral oximetry. Conclusion The model described here seems useful to understand some of the pathophysiological characteristics of acute IH.

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Melatonin-Pretreated Mesenchymal Stem Cells Improved Cognition in a Diabetic Murine Model

Frontiers in Physiology ◽

10.3389/fphys.2021.628107 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shaimaa Nasr Amin ◽

Nivin Sharawy ◽

Nashwa El Tablawy ◽

Dalia Azmy Elberry ◽

Mira Farouk Youssef ◽

...

Keyword(s):

Diabetes Mellitus ◽

Stem Cells ◽

Animal Model ◽

Mesenchymal Stem Cells ◽

Synaptic Plasticity ◽

Object Recognition ◽

Ex Vivo ◽

Type I ◽

Positive Effects ◽

Tnf Α

Diabetes mellitus (DM) is a multisystem endocrine disorder affecting the brain. Mesenchymal stem cells (MSCs) pretreated with Melatonin have been shown to increase the potency of MSCs. This work aimed to compare Melatonin, stem cells, and stem cells pretreated with Melatonin on the cognitive functions and markers of synaptic plasticity in an animal model of type I diabetes mellitus (TIDM). Thirty-six rats represented the animal model; six rats for isolation of MSCs and 30 rats were divided into five groups: control, TIDM, TIDM + Melatonin, TIDM + Stem cells, and TIDM + Stem ex vivo Melatonin. Functional assessment was performed with Y-maze, forced swimming test and novel object recognition. Histological and biochemical evaluation of hippocampal Neuroligin 1, Sortilin, Brain-Derived Neurotrophic Factor (BDNF), inducible nitric oxide synthase (iNOS), toll-like receptor 2 (TLR2), Tumor necrosis factor-alpha (TNF-α), and Growth Associated Protein 43 (GAP43). The TIDM group showed a significant decrease of hippocampal Neuroligin, Sortilin, and BDNF and a significant increase in iNOS, TNF-α, TLR2, and GAP43. Melatonin or stem cells groups showed improvement compared to the diabetic group but not compared to the control group. TIDM + Stem ex vivo Melatonin group showed a significant improvement, and some values were restored to normal. Ex vivo melatonin-treated stem cells had improved spatial working and object recognition memory and depression, with positive effects on glucose homeostasis, inflammatory markers levels and synaptic plasticity markers expression.

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The association between a metabolically healthy overweight/obesity phenotype and markers of inflammation among Chinese children and adolescents aged 10–18 years

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2021-0224 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Jinyu Zhou ◽

Ling Bai ◽

Yangyang Dong ◽

Rongrong Cai ◽

Wenqing Ding

Keyword(s):

Children And Adolescents ◽

Inflammatory Markers ◽

Normal Weight ◽

Chinese Children ◽

Metabolic Phenotypes ◽

Tnf Α ◽

Metabolically Healthy ◽

Hs Crp ◽

The Relationship ◽

Chinese Children And Adolescents

Abstract Objectives The association between metabolically healthy overweight/obesity (MHO) and inflammatory markers remains controversial. The aim of the present study was to describe the prevalence of different metabolic phenotypes and to examine the relationship of different metabolic phenotypes with inflammatory markers among Chinese children and adolescents. Methods The study included 1,125 children and adolescents aged 10–18 years using a cross-sectional survey, and all subjects were classified into four groups based on a combination of BMI and metabolic status. In addition, the inflammatory markers we measured were high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Results The prevalence of metabolically healthy with normal-weight (MHNW), MHO, metabolically unhealthy with normal-weight (MUNW), and metabolically unhealthy overweight/obesity (MUO) phenotypes was 38.76, 7.11, 38.67 and 15.47%, respectively. The results of logistic regression analysis showed that the MHO was associated with the z scores of hs-CRP in Chinese children and adolescents (OR=0.57, 95% CI: 0.39–0.83). Meanwhile, multivariate adjusted regression analysis showed that the relationship between hs-CRP and MHO among the overweight/obese was consistent with the results above, but among the normal-weight, only the highest quartile of TNF-α could increase the risk of MUNW (OR=1.65, 95% CI: 1.09–2.52). Conclusions MHO phenotypes were not common in Chinese children and adolescents. Individuals with MHO had a more beneficial hs-CRP profile than those with MUO.

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