scholarly journals Assessment of the Effects of Stretch-Injury on Primary Rat Microglia

2020 ◽  
Author(s):  
Mike Shaughness ◽  
Kimberly Byrnes
Keyword(s):  
Time Course ◽  
Cell Injury ◽  
Mechanical Stretch ◽  
Course Evaluation ◽  
Cell Diameter ◽  
Exclusion Zone ◽  
Post Injury ◽  
Stretch Injury ◽  
Arginase 1 ◽  
A Cell

Abstract Background: Mechanical stretch-injury is a prominent force involved in the etiology of traumatic brain injury (TBI). It is known to directly cause damage and dysfunction in neurons, astrocytes, and endothelial cells. However, the deleterious effects of stretch-injury on microglia, the brain’s primary immunocompetent cell, are currently unknown. Methods: The Cell Injury Controller II (CICII), a validated model of cellular neurotrauma, was used to induce a mechanical stretch-injury in primary rat microglia. Statistical analysis utilized student t-test and one and two way-ANOVAs with Tukey’s and Sidak’s multiple comparisons, respectively. Results: Cells exposed to stretch-injury showed no signs of membrane permeability, necrosis, or apoptosis, as measured by media derived lactate dehydrogenase (LDH) and cleaved-caspase 3 immunocytochemistry, respectively. Interestingly, injured cells displayed a functional deficit in production nitric oxide (NO), identified by media assay and immunocytochemistry, at 6, 12, 18, and 48 hours post-injury. Furthermore, gene expression analysis revealed the expression of inflammatory cytokines IL-6 and IL-10 and enzyme arginase-1 was significantly down-regulated at 12 hours post-injury. Time course evaluation of migration, using a cell exclusion zone assay, showed stretch-injured cells display decreased migration into the exclusion zone at 48 and 72 hours post-stretch. Lastly, coinciding with the functional immune deficits, was a significant change in morphology, with process length decreasing and cell diameter increasing following an injury at 12 hours. Conclusions: Taken together, the data demonstrate that stretch-injury produces significant alterations in microglial function, which may have marked impact on their response to injury or their interaction with other cells.

Targeting Platelets Containing Electro-encapsulated lloprost to Balloon Injured Aorta in Rats

1995 ◽  
Vol 73 (03) ◽  
pp. 535-542 ◽  
Author(s):  
N Crawford ◽  
A Chajara ◽  
G Pfliegler ◽  
B EI Gamal ◽  
L Brewer ◽  
...  
Keyword(s):  
Time Course ◽  
Therapeutic Potential ◽  
Simple Procedure ◽  
Rat Aorta ◽  
Balloon Injury ◽  
Post Injury ◽  
Antiproliferative Effects ◽  
Platelet Deposition ◽  
Total Dna ◽  
Novel Drug

SummaryDrugs can be electro-encapsulated within platelets and targeted to damaged blood vessels by exploiting the platelet’s natural haemostatic properties to adhere to collagen and other vessel wall constituents revealed by injury. A rat aorta balloon angioplasty model has been used to study the effect on platelet deposition of giving iloprost loaded platelets i.v. during the balloon injury. After labelling the circulating platelets with 111-Indium before balloon injury, time course studies showed maximum platelet deposition on the injured aorta occurred at about 1 h post-injury and the deposition remained stable over the next 2-3 h. When iloprost-loaded platelets were given i.v. during injury and the circulating platelet pool labelled with 111-Indium 30 min later, platelet deposition, measured at 2 h postinjury, was substantially and significantly reduced compared with control platelet treatment. Some antiproliferative effects of iloprost-loaded platelets given i.v. during injury have also been observed. Whereas the incorporation of [3H]-thymidine into aorta intima-media DNA at 3 days post injury was 62-fold higher in balloon injured rats than in control sham operated rats, thymidine incorporation into intima/media of rats which had received iloprost loaded platelets during injury was reduced as compared with rats subjected only to the injury procedure. The reduction was only of near significance, however, but at 14 days after injury the total DNA content of the aorta intima/media of rats given iloprost loaded platelets during injury was significantly reduced. Although iloprost loaded platelets can clearly inhibit excessive platelet deposition, other encapsulated agents may have greater anti-proliferative effects. These studies have shown that drug loaded platelets can be targeted to injured arteries, where they may be retained as depots for local release. We believe this novel drug delivery protocol may have therapeutic potential in reducing the incidence of occlusion and restenosis after angioplasty and thrombolysis treatment. Electro-encapsulation of drugs into platelets is a simple procedure and, using autologous and fully biocompatible and biodegradable platelets as delivery vehicles, might overcome some of the immunological and toxicological problems which have been encountered with other delivery vectors such as liposomes, microbeads, synthetic microcapsules and antibodies.

scholarly journals Frequency of myelin oligodendrocyte glycoprotein antibodies in a large cohort of neurological patients

2021 ◽  
Vol 7 (2) ◽  
pp. 205521732110227
Author(s):  
Friederike Held ◽  
Sudhakar Reddy Kalluri ◽  
Achim Berthele ◽  
Ana-Katharina Klein ◽  
Markus Reindl ◽  
...  
Keyword(s):  
Time Course ◽  
Neurological Diseases ◽  
External Validation ◽  
Diagnostic Value ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Large Cohort ◽  
Wide Range ◽  
Neurological Patients ◽  
A Cell ◽  
Nosological Entity

Background Myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOG-AD) is recognized as a distinct nosological entity. IgG antibodies against MOG (MOG-Ab) overlap with neuromyelitis optica spectrum disorders (NMOSD) phenotype in adults. However, an increasing number of clinical phenotypes have been reported to be associated with MOG-Ab. Objective To investigate the seroprevalence of MOG-Ab under consideration of demographics, disease entities and time course in a large cohort of unselected neurological patients. Methods Blood samples of 2.107 consecutive adult neurologic patients admitted to our department between 2016-2017 were tested for MOG-Ab using a cell-based assay. MOG-Ab persistence was analyzed in follow-up samples. External validation was performed in two independent laboratories. Results We found MOG-Ab in 25 of 2.107 (1.2%) patients. High antibody ratios were mostly associated with NMOSD and MOG-AD phenotype (5/25). Low ratios occurred in a wide range of neurological diseases, predominantly in other demyelinating CNS diseases (5/25) and stroke (6/25). MOG-Ab persistence over time was not confined to NMOSD and MOG-AD phenotype. Conclusion The present study demonstrates the occurrence of MOG-Ab in a wide range of neurological diseases. Only high MOG-Ab ratios were associated with a defined clinical phenotype, but low MOG-Ab ratios were not. The diagnostic value of low MOG-Ab is thus highly limited.

scholarly journals Time-course evaluation of blood glucose changes in response to insulin delivery in critically ill patients

Critical Care ◽  
2014 ◽  
Vol 18 (Suppl 1) ◽  
pp. P440
Author(s):  
F Bass ◽  
S Bird ◽  
N Hammond ◽  
J Myburgh ◽  
S Finfer
Keyword(s):  
Blood Glucose ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Time Course ◽  
Insulin Delivery ◽  
Course Evaluation

Differential expression of TNF-α, IL-6, and IGF-1 by graded mechanical stress in normal rat myocardium

2002 ◽  
Vol 282 (3) ◽  
pp. H926-H934 ◽  
Author(s):  
Emiliano A. Palmieri ◽  
Giulio Benincasa ◽  
Francesca Di Rella ◽  
Cosma Casaburi ◽  
Maria G. Monti ◽  
...  
Keyword(s):  
Time Course ◽  
De Novo ◽  
Mechanical Stretch ◽  
Progressive Increase ◽  
Compensatory Hypertrophy ◽  
Current Data ◽  
Rat Myocardium ◽  
Tnf Α ◽  
Normal Rat ◽  
Necrosis Factor

An isovolumic normal rat heart Langendorff model was used to examine the effects of moderate (15 mmHg) and severe (35 mmHg) mechanical stretch on the time course (from 0 to 60 min) of myocardial expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and insulin-like growth factor (IGF)-1 and their cognate receptors. After 10 min of moderate stretch, TNF-α was de novo expressed, whereas constitutive IL-6 and IGF-1 levels were slightly upregulated; no further changes occurred up to 60 min. In comparison, severe stretch resulted in a higher and progressive increase in TNF-α, IL-6, and IGF-1 expression up to 20 min. After 20 min, whereas TNF-α expression further increased, IL-6 and IGF-1 levels progressively reduced to values lower than those observed under moderate stretch and in unstretched (5 mmHg) control myocardium (IL-6). Mechanical stretch did not significantly alter the expression of the cognate receptors. Indeed, the TNF-α receptor (p55) tended to be progressively upregulated under severe stretch over time. The current data provide the first demonstration that TNF-α, IL-6, and IGF-1 ligand-receptor systems are differentially expressed within the normal rat myocardium in response to graded mechanical stretch. Such findings may have potential implications with regard to compensatory hypertrophy and failure.

scholarly journals Spontaneous one-kidney rats are more susceptible to develop hypertension by DOCA-NaCl and subsequent kidney injury compared with uninephrectomized rats

2016 ◽  
Vol 310 (10) ◽  
pp. F1054-F1064 ◽  
Author(s):  
Xuexiang Wang ◽  
Ashley C. Johnson ◽  
Jennifer M. Sasser ◽  
Jan M. Williams ◽  
Leah C. Solberg Woods ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Kidney Function ◽  
Time Course ◽  
Kidney Injury ◽  
Solitary Kidney ◽  
Course Evaluation ◽  
Significant Rise ◽  
Kidney Weight ◽  
Unilateral Renal Agenesis ◽  
Single Kidney

There is little clinical data of how hypertension may influence individuals with nephron deficiency in the context of being born with a single kidney. We recently developed a new rat model (the heterogeneous stock-derived model of unilateral renal agenesis rat) that is born with a single kidney and exhibits progressive kidney injury and decline in kidney function with age. We hypothesized that DOCA-salt would induce a greater increase in blood pressure and therefore accelerate the progression of kidney injury in rats born with a solitary kidney compared with rats that have undergone unilateral nephrectomy. Time course evaluation of blood pressure, kidney injury, and renal hemodynamics was performed in the following six groups of animals from weeks 13 to 18: 1) DOCA-treated rats with a solitary kidney (DOCA+S group), 2) placebo-treated rats with a solitary kidney, 3) DOCA-treated control rats with two kidneys (DOCA+C group), 4) placebo-treated control rats with two kidneys, 5) DOCA-treated rats with two kidneys that underwent uninephrectomy (DOCA+UNX8 group), and 6) placebo-treated rats with two kidneys that underwent uninephrectomy. DOCA+S rats demonstrated a significant rise ( P < 0.05) in blood pressure (192 ± 4 mmHg), proteinuria (205 ± 31 mg/24 h), and a decline in glomerular filtration rate (600 ± 42 μl·min−1·g kidney weight−1) relative to the DOCA+UNX8 (173 ± 3 mmHg, 76 ± 26 mg/24 h, and 963 ± 36 μl·min−1·g kidney weight−1) and DOCA+C (154 ± 2 mmHg, 7 ± 1 mg/24 h, and 1,484 ± 121 μl·min−1·g kidney weight−1) groups. Placebo-treated groups showed no significant change among the three groups. An assessment of renal injury markers via real-time PCR/Western blot analysis and histological analysis was concordant with the measured physiological parameters. In summary, congenital solitary kidney rats are highly susceptible to the induction of hypertension compared with uninephrectomized rats, suggesting that low nephron endowment is an important driver of elevated blood pressure, hastening nephron injury through the transmission of elevated systemic blood pressure and thereby accelerating decline in kidney function.

scholarly journals Time-course evaluation of intestinal structural disorders in a porcine model of intra-abdominal hypertension by mechanical intestinal obstruction

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0191420 ◽  
Author(s):  
Ester Párraga Ros ◽  
Laura Correa-Martín ◽  
Francisco M. Sánchez-Margallo ◽  
Irma Eugenia Candanosa-Aranda ◽  
Manu L. N. G. Malbrain ◽  
...  
Keyword(s):  
Intestinal Obstruction ◽  
Time Course ◽  
Porcine Model ◽  
Course Evaluation ◽  
Mechanical Intestinal Obstruction ◽  
Structural Disorders ◽  
Abdominal Hypertension

miR-30e-5p regulates autophagy and apoptosis by targeting Beclin1 involved in contrast-induced acute kidney injury

2021 ◽  
Vol 28 ◽  
Author(s):  
Xiaoqin Liu ◽  
Qingzhao Li ◽  
Lixin Sun ◽  
Limei Chen ◽  
Yue Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Kidney Injury ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Cell Model ◽  
Kidney Injury ◽  
Cell Vitality ◽  
A Cell ◽  
Renal Tubular ◽  
Induced Apoptosis

Aims: This study aims to verify if miR-30e-5p targets Beclin1 (BECN1), a key regulator of autophagy, and investigate the function of miR-30e-5p and Beclin1 through mediating autophagy and apoptosis in contrast-induced acute kidney injury (CI-AKI). Methods: Human renal tubular epithelial HK-2 cells were treated with Urografin to construct a cell model of CI-AKI. Real-time reverse transcription–polymerase chain reaction was used to detect gene expression. The dual-luciferase reporting assay and endogenous validation were used to verify targeting and regulating function. The expressions of protein were detected using Western blot. Cell proliferation was detected using methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. Cell apoptosis was detected using terminal-deoxynucleoitidyl transferase mediated nick end labeling assay, and autophagy was detected using transmission electron microscopy. Results: HK-2 cells exposed to Urografin for 2 h induced a significant increase in miR-30e-5p. miR-30e-5p had a targeting effect on Beclin1. Moreover, Urografin exposure can enhance cell apoptosis by increasing caspase 3 gene expression and inhibiting autophagy, which was induced by decreased Beclin1 expression regulated by miR-30e-5p, thereby resulting in renal cell injury. Downregulation of miR-30e-5p or upregulation of Beclin1 restored cell vitality by promoting autophagy and suppressing apoptosis in Urografin-treated cells. Conclusions: Urografin increased the expression of miR-30e-5p in HK-2 cells and thus decreased Beclin1 levels to inhibit autophagy, but induced apoptosis, which may be the mechanism for CI-AKI.

Abstract 153: Born with a Single Kidney versus Nephrectomy: Similar End Point, Different Mechanism of Injury

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Xuexiang Wang ◽  
Ashley Johnson ◽  
Jonathan Lee ◽  
Leah Solberg-Woods ◽  
Michael R Garrett
Keyword(s):  
Renal Function ◽  
Renal Injury ◽  
Time Course ◽  
Course Evaluation ◽  
Pathophysiological Mechanism ◽  
Mechanism Of Injury ◽  
Nephron Number ◽  
Unilateral Renal Agenesis ◽  
Renal Ablation ◽  
Single Kidney

A relatively common abnormality of the urogenital tract in humans is the development of only a single kidney (1:500 to 1:1000). Clinical studies suggest that patients born with a single kidney can develop proteinuria, hypertension, and even renal failure later in life. In contrast, studies in children who undergo nephrectomy or adults who serve as kidney donors appear to exhibit little difference in renal function compared to two-kidney subjects. Invasive techniques such as nephrectomy or renal ablation have been used to generate animal models to recapitulate this human congenital disorder. The progression of injury in these models is attributed to hyperfiltration which refers to changes in hemodynamics that cause glomerular damage leading to hypertension. Recently, our lab developed a new genetic animal model [heterogeneous stock derived model of unilateral renal agenesis, (HSRA)] that develops with a single kidney in 50-75% of offspring. The model is characterized by reduced nephron number, kidney hypertrophy, and renal injury that leads to a decline in renal function. Time course evaluation of blood pressure, renal hemodynamics, and renal injury was performed in 4 groups; (1) HSRA-S (1-kidney), (2) HSRA-C (2-kidney littermates), (3) HSRA-UNX3 (uninephrectomy-week 3) and (4) HSRA-UNX8 (uninephrectomy-week 8). Nephrectomized animals demonstrated hyperfiltration, whereas single kidney animals (HSRA-S) did not. This suggests a different pathophysiological mechanism of injury between congenital and nephrectomized rats. At later time points, proteinuria for HSRA-UNX3 (82±22.9 mg/24h) and HSRA-UNX8 (46±18.1) were significantly higher than HSRA-C (11±6.4), while HSRA-S (109±15.7) demonstrated the highest proteinuria. GFR was lowest in HSRA-S (656±123.9 ul/min/gKW), followed by HSRA-UNX3 (1151±112.4), HSRA-UNX8 (1309±98.3) and HSRA-C (1544±111.7). Microarray studies have identified several developmental genes ( Hox5b , Smoc2 and c- Kit ) that may be linked to reduced nephron number and other structural changes that could predispose the HSRA-S to kidney injury later in life. These results demonstrate that rats born with a single kidney are more prone to renal injury than nephrectomized rats and the mechanism is likely different.

scholarly journals Early pH Changes in Musculoskeletal Tissues upon Injury—Aerobic Catabolic Pathway Activity Linked to Inter-Individual Differences in Local pH

2020 ◽  
Vol 21 (7) ◽  
pp. 2513 ◽  
Author(s):  
Julia C. Berkmann ◽  
Aaron X. Herrera Martin ◽  
Agnes Ellinghaus ◽  
Claudia Schlundt ◽  
Hanna Schell ◽  
...  
Keyword(s):  
Individual Differences ◽  
Animal Models ◽  
Time Course ◽  
Tricarboxylic Acid Cycle ◽  
Controlled Drug Release ◽  
Post Injury ◽  
Ph Changes ◽  
Ph Values ◽  
Local Ph

Local pH is stated to acidify after bone fracture. However, the time course and degree of acidification remain unknown. Whether the acidification pattern within a fracture hematoma is applicable to adjacent muscle hematoma or is exclusive to this regenerative tissue has not been studied to date. Thus, in this study, we aimed to unravel the extent and pattern of acidification in vivo during the early phase post musculoskeletal injury. Local pH changes after fracture and muscle trauma were measured simultaneously in two pre-clinical animal models (sheep/rats) immediately after and up to 48 h post injury. The rat fracture hematoma was further analyzed histologically and metabolomically. In vivo pH measurements in bone and muscle hematoma revealed a local acidification in both animal models, yielding mean pH values in rats of 6.69 and 6.89, with pronounced intra- and inter-individual differences. The metabolomic analysis of the hematomas indicated a link between reduction in tricarboxylic acid cycle activity and pH, thus, metabolic activity within the injured tissues could be causative for the different pH values. The significant acidification within the early musculoskeletal hematoma could enable the employment of the pH for novel, sought-after treatments that allow for spatially and temporally controlled drug release.

scholarly journals Longitudinal Changes in Disability Rating Scale Scores: A Secondary Analysis Among Patients With Severe TBI Enrolled in the Epo Clinical Trial

2019 ◽  
Vol 25 (3) ◽  
pp. 293-301 ◽  
Author(s):  
Julia S. Benoit ◽  
H. Julia Hannay ◽  
Jose-Miguel Yamal ◽  
David J. Francis ◽  
Imoigele Aisiku ◽  
...  
Keyword(s):  
Dynamic Process ◽  
Time Course ◽  
Injury Severity ◽  
Rating Scale ◽  
Outcome Measurement ◽  
Response To Treatment ◽  
Post Injury ◽  
Transfusion Threshold ◽  
Disability Rating Scale ◽  
Disability Rating

AbstractObjectives:Long-term neurological response to treatment after a severe traumatic brain injury (sTBI) is a dynamic process. Failure to capture individual heterogeneity in recovery may impact findings from single endpoint sTBI randomized controlled trials (RCT). The present study re-examined the efficacy of erythropoietin (Epo) and transfusion thresholds through longitudinal modeling of sTBI recovery as measured by the Disability Rating Scale (DRS). This study complements the report of primary outcomes in the Epo sTBI RCT, which failed to detect significant effects of acute treatment at 6 months post-injury.Methods:We implemented mixed effects models to characterize the recovery time-course and to examine treatment efficacy as a function of time post-injury and injury severity.Results:The inter-quartile range (25th–75thpercentile) of DRS scores was 20–28 at week1; 8–24 at week 4; and 3–17 at 6 months. TBI severity group was found to significantly interact with Epo randomization group on mean DRS recovery curves. No significant differences in DRS recovery were found in transfusion threshold groups.Conclusions:This study demonstrated the value of taking a comprehensive view of recovery from sTBI in the Epo RCT as a temporally dynamic process that is shaped by both treatment and injury severity, and highlights the importance of the timing of primary outcome measurement. Effects of Epo treatment varied as a function of injury severity and time. Future studies are warranted to understand the possible moderating influence of injury severity on treatment effects pertaining to sTBI recovery. (JINS, 2019,25, 293–301)

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