scholarly journals Tumor necrosis factor-α inhibition attenuates middle cerebral artery remodeling but increases cerebral ischemic damage in hypertensive rats

2014 ◽  
Vol 307 (5) ◽  
pp. H658-H669 ◽  
Author(s):  
Paulo W. Pires ◽  
Saavia S. Girgla ◽  
Guillermo Moreno ◽  
Jonathon L. McClain ◽  
Anne M. Dorrance
Keyword(s):  
Cerebral Ischemia ◽  
Tumor Necrosis Factor ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Tumor Necrosis ◽  
Myogenic Tone ◽  
Hypertensive Rats ◽  
Tnf Α ◽  
Necrosis Factor

Hypertension causes vascular inflammation evidenced by an increase in perivascular macrophages and proinflammatory cytokines in the arterial wall. Perivascular macrophage depletion reduced tumor necrosis factor (TNF)-α expression in cerebral arteries of hypertensive rats and attenuated inward remodeling, suggesting that TNF-α might play a role in the remodeling process. We hypothesized that TNF-α inhibition would improve middle cerebral artery (MCA) structure and reduce damage after cerebral ischemia in hypertensive rats. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were treated with the TNF-α inhibitor etanercept (ETN; 1.25 mg·kg−1·day−1 ip daily) or PBS (equivolume) for 6 wk. The myogenic tone generation, postischemic dilation, and passive structure of MCAs were assessed by pressure myography. Cerebral ischemia was induced by MCA occlusion (MCAO). Myogenic tone was unchanged, but MCAs from SHRSP + ETN had larger passive lumen diameter and reduced wall thickness and wall-to-lumen ratio. Cerebral infarct size was increased in SHRSP + ETN after transient MCAO, despite an improvement in dilation of nonischemic MCA. The increase in infarct size was linked to a reduction in the number of microglia in the infarct core and upregulation of markers of classical macrophage/microglia polarization. There was no difference in infarct size after permanent MCAO or when untreated SHRSP subjected to transient MCAO were given ETN at reperfusion. Our data suggests that TNF-α inhibition attenuates hypertensive MCA remodeling but exacerbates cerebral damage following ischemia/reperfusion injury likely due to inhibition of the innate immune response of the brain.

Epidermal growth factor, tumor necrosis factor alpha, and thioredoxin in cerebral tissue following cerebral ischemia / Serebral iskemi sonrası beyin dokusunda epidermal büyüme faktörü, tümör nekrozis faktör alfa ve tiyoredoksin

2015 ◽  
Vol 40 (6) ◽  
Author(s):  
Hatice Ferhan Kömürcü ◽  
Nedret Kılıç ◽  
Melike Erol Demirbilek ◽  
Serdar Kahraman
Keyword(s):  
Cerebral Ischemia ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cerebral Tissue ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Epidermal Growth ◽  
Factor Alpha ◽  
Necrosis Factor

AbstractObjective: In this study, the changes in the levels of the epidermal growth factor (EGF), tumor necrosis factor alpha (TNF-α), and thioredoxine (TRX) in the cerebral tissue of rats following the cerebral ischemia model were investigated.Methods: The left middle cerebral artery occlusion (MCAO) was done in 27 out of 48 rats recruited into the study for obtaining focal cerebral ischemia model (MCAO group). Twenty-one rats underwent a sham operation; the middle cerebral artery was exposed but not occluded (Sham group). EGF, TNF-α, and TRX levels were studied in the operated left and contralateral hemispheres at the 16Results: EGF levels at 96Conclusion: The results suggested that cerebral ischemia following MCAO might affect EGF, TNF-α and TRX levels in both ischemic and contralateral hemispheres in cerebral tissue; and this effect may change by the time passed after MCAO.

scholarly journals Investigation of Epidermal Growth Factor, Tumor Necrosis Factor-alpha and Thioredoxin System in Rats Exposed to Cerebral Ischemia

2016 ◽  
Vol 24 (3) ◽  
pp. 307-317
Author(s):  
Melike Erol-Demirbilek ◽  
Nedret Kilic ◽  
Hatice Ferhan Komurcu
Keyword(s):  
Cerebral Ischemia ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Epidermal Growth Factor ◽  
Tumor Necrosis ◽  
Tnf Α ◽  
Thioredoxin System ◽  
Epidermal Growth ◽  
Cerebral Ischemic ◽  
Necrosis Factor

Abstract Background: Thioredoxin reductase (TrxR), epidermal growth factor (EGF) and tumor necrosis factor-α (TNF-α) have neuroprotective/neurotoxic effects in cerebral ischemia. We aimed to investigate the TrxR activity, EGF and TNF-α levels in cerebral ischemic, sham-operated and non-ischemic rat brains. Methods: Sprague-Dawley rats divided into three groups. Rats in control group were not subjected to any of treatments and their brains were removed under anesthesia. Middle cerebral arters were exposed but not occluded for the sham-operated rats. Animals were subjected to permanent middle cerebral arter occlusion (MCAO) in MCAO-operated group. The rats were decapitated at 16 hours (h), 48 h and 96 h after sham operation and focal cerebral ischemia. TrxR activities, EGF and TNF-α levels were measured in ischemic and non-ischemic hemispheres for all groups. Results: In group MCAO, TrxR activities were significantly low at 48 h in ischemic hemisphere in comparison to control. After the 48 h, a remarkable increase was observed at 96 h. EGF and TNF-α levels were substantially high at 96 h in group MCAO of ischemic brain. Conclusion: TrxR activity was reduced by oxidative stress which was formed by ischemia. EGF levels increased to exhibit neurotrophic and neuroprotective effects. After ischemia, TNF-α levels increased as a response to the tissue damage. Further studies with a higher number of experimental subjects and shorter or longer periods such as from first 30 minutes up to 3 months may be more informative to show the time-dependent variations in TrxR, EGF and TNF-α in cerebral ischemic injury.

#50 Gestational exposure of tumor necrosis factor-α (TNF-α) inhibitor drugs

2019 ◽  
Vol 88 ◽  
pp. 149-150 ◽  
Author(s):  
Erkoseoglu Ilknur ◽  
Kadioglu Mine ◽  
Cavusoglu Irem ◽  
Sisman Mulkiye ◽  
Aran Turhan ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Gestational Exposure ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Association of tumor necrosis factor-alpha -308 G/A and -238 G/A polymorphism with diabetic retinopathy: a systematic review and updated meta-analysis.

2020 ◽  
Author(s):  
Wenna Gao ◽  
Ruilin Zhu ◽  
liu yang
Keyword(s):  
Diabetic Retinopathy ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Meta Analysis ◽  
Entire Group ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Background: Mounting evidence has suggested tumor necrosis factor-alpha (TNF-α) can promote the development of diabetic retinopathy (DR), and TNF-α gene variants may influence DR risk. However, the results are quite different. Objectives: To comprehensively address this issue, we performed the meta-analysis to evaluate the association of TNF-α-308 G/A and -238 G/A polymorphism with DR. Method: Data were retrieved in a systematic manner and analyzed using STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Allelic and genotypic comparisons between cases and controls were evaluated. Results: For the TNF-α-308 G/A polymorphism, overall analysis suggested a marginal association with DR [the OR(95%CI) of (GA versus GG), (GA + AA) versus GG, and (A versus G) are 1.21(1.04, 1.41), 1.20(1.03, 1.39), and 1.14(1.01, 1.30), respectively]. And the subgroup analysis indicated an enhanced association among the European population. For the TNF-α-238 G/A polymorphism, there was mild correlation in the entire group [the OR(95%CI) of (GA versus GG) is 1.55(1.14,2.11) ], which was strengthened among the Asian population. Conclusion: The meta-analysis suggested that -308 A and -238 A allele in TNF-α gene potentially increased DR risk and showed a discrepancy in different ethnicities.

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