scholarly journals Prolonged, 24-h Delayed Peripheral Inflammation Increases Short- and Long-Term Functional Impairment and Histopathological Damage after Focal Ischemia in the Rat

2010 ◽  
Vol 30 (8) ◽  
pp. 1450-1459 ◽  
Author(s):  
Kristopher D Langdon ◽  
Crystal L MacLellan ◽  
Dale Corbett

The incidence of infection among stroke patients is alarmingly high and both acute and delayed infections increase morbidity and mortality. Experimental studies support the acute clinical data, but little attention has focused on delayed systemic infections. Here, we investigated the effects of prolonged systemic inflammation either before or 24-h after ischemia. Systemic inflammation was induced by injecting rats with three separate doses of lipopolysaccharide (LPS; 50 μg/kg, i.p.) with core temperature monitoring for 48-h after middle cerebral artery occlusion (MCAo). Lipopolysaccharide injected before MCAo increased injury by ∼30%, whereas delayed injection increased injury by ∼85% (30-day survival). Proinflammatory cytokines assessed repeatedly for 72 h were significantly and persistently elevated with inflammation. This was accompanied by increases in microglia/macrophage and infiltrating leukocyte numbers in delayed LPS-treated animals. Behavioral assessments at 7 and 30 days revealed ∼15% deficit in hindlimb function in animals treated with LPS 24-h after ischemia. Clearly, delayed and prolonged postischemic systemic inflammation has devastating effects on stroke outcome, in the absence of a prolonged febrile response. These findings, together with corroborative clinical data, emphasize the importance of early intervention to counteract the deleterious consequences of stroke-associated inflammation and infection.

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Adrien Cogo ◽  
Gabrielle Mangin ◽  
Benjamin Maïer ◽  
Jacques Callebert ◽  
Mikael Mazighi ◽  
...  

Abstract Background Strokes are becoming less severe due to increased numbers of intensive care units and improved treatments. As patients survive longer, post-stroke cognitive impairment (PSCI) has become a major health public issue. Diabetes has been identified as an independent predictive factor for PSCI. Here, we characterized a clinically relevant mouse model of PSCI, induced by permanent cerebral artery occlusion in diabetic mice, and investigated whether a reliable biomarker of PSCI may emerge from the kynurenine pathway which has been linked to inflammatory processes. Methods Cortical infarct was induced by permanent middle cerebral artery occlusion in male diabetic mice (streptozotocin IP). Six weeks later, cognitive assessment was performed using the Barnes maze, hippocampi long-term potentiation using microelectrodes array recordings, and neuronal death, white matter rarefaction and microglia/macrophages density assessed in both hemispheres using imunohistochemistry. Brain and serum metabolites of the kynurenin pathway were measured using HPLC and mass fragmentography. At last, these same metabolites were measured in the patient’s serum, at the acute phase of stroke, to determine if they could predict PSCI 3 months later. Results We found long-term spatial memory was impaired in diabetic mice 6 weeks after stroke induction. Synaptic plasticity was completely suppressed in both hippocampi along with increased neuronal death, white matter rarefaction in both striatum, and increased microglial/macrophage density in the ipsilateral hemisphere. Brain and serum quinolinic acid concentrations and quinolinic acid over kynurenic acid ratios were significantly increased compared to control, diabetic and non-diabetic ischemic mice, where PSCI was absent. These putative serum biomarkers were strongly correlated with degradation of long-term memory, neuronal death, microglia/macrophage infiltration and white matter rarefaction. Moreover, we identified these same serum biomarkers as potential predictors of PSCI in a pilot study of stroke patients. Conclusions we have established and characterized a new model of PSCI, functionally and structurally, and we have shown that the QUIN/KYNA ratio could be used as a surrogate biomarker of PSCI, which may now be tested in large prospective studies of stroke patients.


2020 ◽  
Vol 45 (3) ◽  
pp. 303-324
Author(s):  
Johannes Beckert ◽  
Thomas Koch ◽  
Benno Viererbl ◽  
Nora Denner ◽  
Christina Peter

AbstractNative advertising has recently become a prominent buzzword for advertisers and publishers alike. It describes advertising formats which closely adapt their form and style to the editorial environment they appear in, intending to hide the commercial character of these ads. In two experimental studies, we test how advertising disclosures in native ads on news websites affect recipients’ attitudes towards a promoted brand in a short and long-term perspective. In addition, we explore persuasion through certain content features (i. e., message sidedness and use of exemplars) and how they affect disclosure effects. Results show that disclosures increase perceived persuasive intent but do not necessarily decrease brand attitudes. However, disclosure effects do not persist over time and remain unaffected by content features.


2017 ◽  
Vol 37 (3) ◽  
pp. 755-761 ◽  
Author(s):  
Jewel Ahmed ◽  
Dominic M Dwyer ◽  
Tracy D Farr ◽  
David J Harrison ◽  
Stephen B Dunnett ◽  
...  

The need for sensitive, easy to administer assessments of long-term functional deficits is crucial in pre-clinical stroke research. In the present study, we introduce lickometry (lick microstructure analysis) as a precise method to assess sensorimotor deficits up to 40 days after middle cerebral artery occlusion in rats. Impairments in drinking efficiency compared to controls, and a compensatory increase in the number of drinking clusters were observed. This highlights the utility of this easy to administer task in assessing subtle, long-term deficits, which could be likened to oral deficits in patients.


2022 ◽  
Vol 11 (6) ◽  
pp. 733-745
Author(s):  
Nora Athmani ◽  
Allaoui Amine ◽  
Nasri Moncef ◽  
Boualga Ahmed

Hypercholesterolemia is a major risk factor of cardiovascular diseases (CVD). A limited number of experimental studies have shown that sardine protein hydrolysates (SPH) could be a very useful natural compound to prevent hy-percholesterolemia by both improving the lipoprotein profile and modula-ting oxidative stress. In the present study, the effect of short and long term treatments with SPH were examined on serum lipid contents, lipid peroxida-tion and antioxidant enzymes activities in rats fed cholesterol-enriched diet. At day 0, rats were divided into five groups. The group of day 0 was the stan-dard group, and the four remaining groups were divided into two parts of two groups each consuming for 14 or 28 days an hypercholesterolemic diet, and treated (HC-SPH) or not (HC) by gavage with SPH. Compared with day 0, serum TC contents were increased at day 14 and remained unchanged at day 28 in HC-SPH group. These values were decreased in HC-SPH versus HC. Liver and heart TBARS concentrations were increased at day 14 then diminished at day 28 in HC-SPH group. Liver and heart SOD and CAT activities were decrea-sed at short term then remained unchanged at long term in HC-SPH group. In addition, these activities were enhanced in HC-SPH versus HC. In conclusion, these results indicate the potential effects of short and long term treatments of SPH to improved cholesterolemia and reduced radical attack in rats fed high-cholesterol diets.


2019 ◽  
Vol 10 ◽  
pp. 143
Author(s):  
Feda Anisah Makkiyah ◽  
Wismaji Sadewo

Background: Although there are many experimental studies describing the suture method of middle cerebral artery occlusion (MCAO) in rats, this is still a new procedure in Indonesia and the techniques for applying this stroke model in animal research are not well known. There has been a perception in Indonesian scientific community that the technique would be difficult and require advanced equipment. The aim of this study is to demonstrate that it is possible to perform the technique with minimal resources using simple method and basic surgical loupe equipment. Methods: A total of 30 male Wistar rats, aged 6 months, weighing 250 g–400 g Wistar rats, were obtained from the Bandung Biofarma Pasteur. Preliminary trials were performed to gain an understanding of the detailed anatomy of the animals and to master the techniques. An ×8 loupe magnification was used for all surgical steps in this study except taking of surgical operation photos. The procedures applied simple methods, using two loop temporary knots instead of any animal vascular clips. Results: After an extensive training period, two of the 30 rats died within 4 weeks after the procedure. The effects of MCAO were confirmed clinically and by hematoxylin-eosin staining pathology slides. Conclusion: With simple methods, this MCAO procedure could be implemented in developing countries such as Indonesia without the requirement for advanced equipment.


2007 ◽  
Vol 106 (1) ◽  
pp. 92-99 ◽  
Author(s):  
Hiroaki Sakai ◽  
Huaxin Sheng ◽  
Robert B. Yates ◽  
Kazuyoshi Ishida ◽  
Robert D. Pearlstein ◽  
...  

Background Long-term neuroprotection by isoflurane has been questioned. The authors examined factors in experimental models potentially critical to definition of enduring isoflurane neuroprotection. Methods Rats were prepared for temporary middle cerebral artery occlusion (MCAO). Pericranial normothermia was maintained. Neurologic deficits (range, 0-48; 0=no deficit) and cerebral infarct volumes were measured. In experiment 1, rats underwent 50 or 80 min MCAO while awake or anesthetized with 1.8% isoflurane. Blood pressure was controlled with phenylephrine. Outcome was evaluated 2 weeks later. In experiment 2, rats underwent 50 min MCAO while awake or anesthetized with isoflurane, with outcome evaluated 8 weeks later. In experiment 3, rats underwent 50 min MCAO while awake or anesthetized with isoflurane and 2 weeks recovery. Effects of phenylephrine and the mitochondrial adenosine triphosphate-sensitive K channel antagonist 5-hydroxydecanoate were studied. In experiment 4, isoflurane-anesthetized rats underwent 50 min MCAO with permanent or temporary common carotid artery occlusion, with outcome evaluated 2 weeks later. Results In experiment 1, isoflurane reduced neurologic deficit (median+/-interquartile range; awake vs. isoflurane: 11+/-12 vs. 8+/-6 for 80 min and 13+/-4 vs. 3+/-9 for 50 min; P=0.0006) and infarct size (160+/-97 vs. 84+/-62 mm for 80 min and 169+/-78 vs. 68+/-61 mm for 50 min; P<0.0001). In experiment 2, isoflurane protection persisted at 8 weeks after ischemia. In experiment 3, there was no effect of phenylephrine or 5-hydroxydecanoate. In experiment 4, permanent common carotid ligation increased infarct size threefold versus temporary occlusion. Conclusions Isoflurane repeatedly improved long-term neurologic and histologic outcome from focal ischemia independent of ischemia duration, perfusion pressure, or pretreatment with 5-hydroxydecanoate.


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