scholarly journals Regulatory effect of Dimethyl Sulfoxide (DMSO) on astrocytic reactivity in a murine model of cerebral infarction by arterial embolization

2013 ◽  
pp. 31-36 ◽  
Author(s):  
Catalina Lapuente ◽  
Carlos A Rengifo ◽  
Marco F Ávila ◽  
Angel E Céspedes
Keyword(s):  
Dimethyl Sulfoxide ◽  
Cellular Response ◽  
Arterial Embolization ◽  
Treated Group ◽  
Experimental Models ◽  
Cerebral Embolism ◽  
Immune Reactivity ◽  
Regulatory Effect ◽  
Nih Image ◽  
Neurologic Recovery

Introduction: The pathophysiology of cerebral ischemia is essential for early diagnosis, neurologic recovery, the early onset of drug treatment and the prognosis of ischemic events. Experimental models of cerebral ischemiac an be used to evaluate the cellular response phenomena and possible neurological protection by drugs. Objective: To characterize the cellular changes in the neuronal population and astrocytic response by the effect of Dimethyl Sulfoxide (DMSO) on a model of ischemia caused by cerebral embolism. Methods: Twenty Wistar rats were divided into four groups (n= 5). The infarct was induced with α-bovinethrombin (40 NIH/U). The treated group received 90 mg (100 µL) of DMSO in saline (1:1 v/v) intraperitoneally for 5 days; ischemic controls received only NaCl (placebo) and two non-ischemic groups (simulated) received NaCl and DMSO respectively. We evaluated the neuronal (anti-NeuN) and astrocytic immune-reactivity (anti-GFAP). The results were analyzed by densitometry (NIH Image J-Fiji 1.45 software) and analysis of variance (ANOVA) with the Graph pad software (Prism 5). Results: Cerebral embolism induced reproducible and reliable lesions in the cortex and hippocampus (CA1). similar to those of focal models. DMSO did not reverse the loss of post-ischemia neuronal immune-reactivity, but prevented the morphological damage of neurons, and significantly reduced astrocytic hyperactivity in thesomato-sensory cortex and CA1 (P <0.001). Conclusions: The regulatory effect of DMSO on astrocyte hyperreactivity and neuronal-astroglial cytoarchitecture, gives it potential neuroprotective properties for the treatment of thromboembolic cerebral ischemiain the acute phase.

scholarly journals Studies of the interaction of ticagrelor with the P2Y13 receptor and with P2Y13-dependent pro-platelet formation by human megakaryocytes

2016 ◽  
Vol 116 (12) ◽  
pp. 1079-1088 ◽  
Author(s):  
Anna Björquist ◽  
Christian A. Di Buduo ◽  
Eti A. Femia ◽  
Robert F. Storey ◽  
Richard C. Becker ◽  
...  
Keyword(s):  
Platelet Count ◽  
Cellular Response ◽  
P2y Receptors ◽  
Cell System ◽  
Experimental Models ◽  
Significant Activity ◽  
Label Free ◽  
Coronary Syndrome ◽  
Platelet Formation

SummaryTicagrelor is an antagonist of the platelet P2Y12 receptor for ADP, approved for the prevention of thromboembolic events in patients with acute coronary syndrome. Previous studies showed that ticagrelor has no significant activity versus P1 receptors for adenosine and other known P2Y receptors, with the exception of P2Y13, which was not tested. The P2Y12 antagonist cangrelor has been shown to also inhibit P2Y13 and to decrease the P2Y13-regulated capacity of megakaryocytes to produce pro-platelets. We tested whether or not ticagrelor inhibits P2Y13 signalling and function. The in vitro effects of ticagrelor, its active (TAM) and inactive (TIM) metabolites, cangrelor and the P2Y13 antagonist MRS2211 were tested in two experimental models: 1) a label-free cellular response assay in P2Y13-transfected HEK293 T-REx cells; and 2) pro-platelet formation by human megakaryocytes in culture. Ticagrelor, TAM, cangrelor and MRS2211, but not TIM, inhibited the cellular responses in P2Y13-transfected cells. In contrast, only MRS2211 and cangrelor, confirming previous results, inhibited pro-platelet formation by megakaryocytes in vitro. The platelet count of patients randomised to treatment with ticagrelor in the PLATO trial did not change during treatment and was comparable to those of patients randomised to clopidogrel. In conclusion, ticagrelor and TAM act as P2Y13 antagonists in a transfected cell system in vitro but this does not translate into any impact on pro-platelet formation in vitro or altered platelet count in patients.

scholarly journals Bipolar radiofrequency ablation of aneurysm remnants after coil embolization can improve endovascular treatment of experimental bifurcation aneurysms

2017 ◽  
Vol 126 (5) ◽  
pp. 1537-1544 ◽  
Author(s):  
Xavier Boileau ◽  
Han Zeng ◽  
Robert Fahed ◽  
Fabrice Bing ◽  
Alina Makoyeva ◽  
...  
Keyword(s):  
Radiofrequency Ablation ◽  
Endovascular Treatment ◽  
Coil Embolization ◽  
Treated Group ◽  
Experimental Models ◽  
Ordinal Scale ◽  
Control Group ◽  
Median Score ◽  
Aneurysm Neck ◽  
Bipolar Radiofrequency

OBJECTIVEEndovascular treatment of aneurysms may result in incomplete initial occlusion and aneurysm recurrence at angiographic follow-up studies. This study aimed to assess the feasibility and efficacy of bipolar radiofrequency ablation (RFA) of aneurysm remnants after coil embolization.METHODSBipolar RFA was accomplished using the coil mass as 1 electrode, while the second electrode was a stent placed across the aneurysmal neck. After preliminary experiments and protocol approval from the Animal Care committee, wide-necked bifurcation aneurysms were constructed in 24 animals. Aneurysms were allocated to 1 of 3 groups: partial intraoperative coil embolization, followed by RFA (n = 12; treated group) or without RFA (n = 6; control group 1); or attempted complete endovascular coil embolization 2–4 weeks later (n = 6; control group 2). Angiographic results were compared at baseline, immediately after RFA, and at 12 weeks, using an ordinal scale. Pathological results and neointima formation at the neck were compared using a semiquantitative grading scale.RESULTSBipolar RFA was able to reliably target the aneurysm neck when the coil mass and stent were used as electrodes. RFA improved angiographic results immediately after partial coiling (p = 0.0024). Two RFA-related complications occurred, involving transient occlusion of 1 carotid artery and 1 hemorrhage from an adventitial arterial blister. At 12 weeks, angiographic results were improved with RFA (median score of 0), when compared with controls (median score of 2; p = 0.0013). Neointimal closure of the aneurysm neck was better with RFA compared with controls (p = 0.0003).CONCLUSIONSBipolar RFA can improve results of embolization in experimental models by selectively ablating residual lesions after coil embolization.

scholarly journals EVALUATION OF PROTECTIVE POTENTIAL OF CITRUS AURANTIFOLIA (CHRISTM) SWINGLE PEEL EXTRACT IN ATTENUATING DOXORUBICIN-INDUCED HEPATOTOXICITY IN EXPERIMENTAL MODELS

2020 ◽  
Vol 10 ◽  
pp. 138
Author(s):  
Oladapo Elijah Oyinloye ◽  
Akinyinka Oyedolapo Alabi ◽  
David Damilola Oluwasusi ◽  
Abdullahi Akanji Murtala ◽  
Adeyinka Aderonke Aderinola ◽  
...  
Keyword(s):  
Liver Enzymes ◽  
Antioxidant Properties ◽  
Study Groups ◽  
Treated Group ◽  
Experimental Models ◽  
Female Rats ◽  
Distilled Water ◽  
Citrus Aurantifolia ◽  
Vacuolar Change ◽  
Peel Extract

Citrus aurantifolia is a very common, and widely cultivated and consumed for its antioxidant properties due to its robust flavonoids content. Doxorubicin (DOX) is an antibiotic broadly used in the treatment of different types of solid tumours, but its use also comes at a cost, organ toxicity. The curative and preventive properties of Citrus aurantifolia  peel extract (CAPE) in doxorubicininduced hepatotoxicity in Wistar rats were evaluated. Thirty female rats were divided into six groups of five (5) rats each in both curative and preventive studies. In curative study, five groups of rats (II – VI) received Doxorubicin (mixed with normal saline, 15 mg/kg body weight i.p) on day one, 24 hours after, graded doses of CAPE and alpha-lipoic acid (A.L.A.) were administered to groups II- V and VI respectively for 7 consecutive days. For the prophylactic study, groups II – V and VI received graded doses of CAPE and A.L.A. respectively, 24 hours after Doxorubicin was administered to groups II-VI. Groups treated with D.W. and A.L.A. were used as a negative and positive control, respectively Liver enzymes such as A.S.T., A.L.T. and A.L.P., including liver samples, were examined for histopathological changes. A significant reduction (p< 0.05) in serum A.S.T. and A.L.T. levels was observed in animals treated with CAPE 200 and 400mg/kg in the preventive study, while in curative, a significant reduction in an expected rise in serum A.S.T., A.L.T. and A.L.P. (p<0.05) was observed in animals treated with CAPE 400mg/kg when compared to the group treated with DOX + distilled water. Hepatocellular necrosis was observed in the histology of DOX- distilled water treated group. Besides, the hepatocytes of groups treated with CAPE (200 and 400mg/kg) in this study showed narrow foci of mild vacuolar change as compared with groups treated with the lowest dose of CAPE (100mg.kg) and distilled water, which revealed random foci of mild vacuolar change. This study has provided information that DOX damaged liver tissue due to an increase in liver enzymes and histopathological results showing tissue damaged in groups treated with lower doses of CAPE and distilled water.  This study further demonstrates that groups treated with CAPE 200, 400 mg/kg and A.L.A. protect hepatic damage induced by DOX.

Effect of traditional herbal formulation on experimental models of ulcerative colitis

2020 ◽  
Vol 10 ◽  
Author(s):  
Sateesha S Boregowda ◽  
Karnati Nithinkumar ◽  
Rajamma A Jayaramu ◽  
Chandan Kalegowda ◽  
Govindareddy Y Avalakondareddy
Keyword(s):  
Ulcerative Colitis ◽  
Artemisia Annua ◽  
Treated Group ◽  
Experimental Models ◽  
Morinda Citrifolia ◽  
Serum Lactate Dehydrogenase ◽  
Standard Drug ◽  
Polyherbal Formulation ◽  
Tissue Weight ◽  
Herbal Formulation

Aims: Evaluation of the effectiveness of herbal formulation consisting Morinda citrifolia L, Artemisia annua L, Glycyrrhiza glabra L and Ocimum basilicum L, in treating ulcerative colitis. Objectives: Assessment of effect of herbal formulation on the indomethacin induced ulcerative colitis based on serum lactate dehydrogenase (LDH) level, tissue myloperoxidase (MPO) activity and colonic glutathione (GSH) content and macroscopic features. Determination of tissue ulcer scores, tissue weight and tissue histopathological changes before and after treatment with herbal formulation in disease induced model. Methods: Herbal formulation from an ancient literature was selected and it is evaluated for its effectiveness against indomethacin-induced ulcerative colitis in rats. Mesalamine was used as a standard drug to compare the effect of herbal formulation on ulcerative colitis. Quantification of serum LDH levels, tissue MPO activity, colonic GSH levels, and the histopathological features of inflammatory and recovered cells were used to establish the efficacy of the formulation. Results: Formulation treatment showed an appreciable increase in the serum GSH levels, and decrease in the tissue MPO activity and serum LDH levels. The results of ulcer score analysis and tissue weight analysis of the formulation treated group were similar to the mesalamine treated group. Histopathological studies reveal a decrease in oedema and reduced inflammation followed by the formulation treatment. Conclusion: The study established the efficacy of polyherbal formulation in the treatment of ulcerative colitis following sub-chronic administration. This analysis also reveals that the polyherbal formulation is effective as mesalamine in the treatment of ulcerative colitis.

Abstract WMP40: Intra-arterial Mesenchymal Stem Cells in a Large Animal Endovascular Canine Stroke Model: Findings on Serial Diffusion Tensor Imaging

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Luis Guada ◽  
Pattany Pradip ◽  
Kevin Ramdas ◽  
Ryan Pafford ◽  
Gaurav Saigal ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Cell Therapy ◽  
Diffusion Tensor ◽  
Artery Occlusion ◽  
Experimental Models ◽  
Large Animal ◽  
White Matter Tracts ◽  
Neurologic Recovery ◽  
Adc Values

Background: Cell therapy is promising in rodent pre-clinical studies. Confirmation of efficacy of this novel approach in large animals is recommended. Diffusion Tensor Imaging (DTI) assesses white matter microstructure in the CNS using Fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Diffusion Tensor Tractography (DTT) DTT produces a 3D representation of the white matter tracts (WMT) in which data are displayed on a colored map that helps to identify the integrity of the tracts selected under the region of Interest (ROI). The purpose of this study was to use DTI-DTT analysis, and correlate it with the neuro-assessment of dogs over one month after ipsilateral intra-arterial (IA) Mesenchymal Stem Cell (MSCs) 48 hours after a brain-stroke was reversible middle cerebral artery occlusion (rMCAo) Methods: Mongrel Hounds (n=5), aged 12-36 months, were included in this pilot study. rMCAo was induced via endovascular approach using a detachable helical ultra-coil over 35-80 min. MSCs (1-20 millions) were infused intra-arterially 48hrs post stroke in the ipsilesional cervical internal carotid. DTI-T images were obtained at 48h post rMCAo pre-IA cell delivery, 15 & 30 days. DTT was also generated. FA-ADC values of the right & left hemisphere and CST were determined. Weekly neuro-evaluations were performed using our canine neuro-scale Results: Our data suggest a correlation between the neurological recovery and improvement in the FA-ADC values (see figure). An increase in the caliber of corticospinal tracts ipsilateral to the stroke by day 30 compared to pre-injection was observed on the DTT reconstruction for two canines that showed neurological improvement ( see figure) Conclusions: Serial DTI-DTT imaging after IA cell therapy shows improvement in white matter tracts correlating with neurologic recovery. This supports further development of DTI-DTT biomarkers to measure neurologic recovery in experimental models as well as early clinical trials.

The impact of dimethyl sulfoxide on oxidative stress and cytotoxicity in various experimental models

Toxicology ◽  
2021 ◽  
pp. 243-261
Author(s):  
Phiwayinkosi V. Dludla ◽  
Bongani B. Nkambule ◽  
Sithandiwe E. Mazibuko-Mbeje ◽  
Tawanda M. Nyambuya ◽  
Sonia Silvestri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dimethyl Sulfoxide ◽  
Experimental Models ◽  
The Impact

scholarly journals Invariant NKT Cells as Novel Targets for Immunotherapy in Solid Tumors

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Karsten A. Pilones ◽  
Joseph Aryankalayil ◽  
Sandra Demaria
Keyword(s):  
Cellular Response ◽  
Antitumor Immunity ◽  
Nkt Cells ◽  
Experimental Models ◽  
Small Population ◽  
Current Data ◽  
Nkt Cell ◽  
Invariant Nkt Cells ◽  
Adaptive Immune Cells ◽  
Infection And Inflammation

Natural killer T (NKT) cells are a small population of lymphocytes that possess characteristics of both innate and adaptive immune cells. They are uniquely poised to respond rapidly to infection and inflammation and produce cytokines that critically shape the ensuing adaptive cellular response. Therefore, they represent promising therapeutic targets. In cancer, NKT cells are attributed a role in immunosurveillance. NKT cells also act as potent activators of antitumor immunity when stimulated with a synthetic agonist in experimental models. However, in some settings, NKT cells seem to act as suppressors and regulators of antitumor immunity. Here we briefly review current data supporting these paradoxical roles of NKT cells and their regulation. Increased understanding of the signals that determine the function of NKT cells in cancer will be essential to improve current strategies for NKT-cell-based immunotherapeutic approaches.

scholarly journals Anticoagulation in Cerebral Embolism

1983 ◽  
Vol 10 (1) ◽  
pp. 32-36 ◽  
Author(s):  
Edward Bass
Keyword(s):  
Experimental Data ◽  
Retrospective Study ◽  
Prospective Studies ◽  
Early Treatment ◽  
Treatment Plan ◽  
Experimental Models ◽  
Cerebral Embolism ◽  
Insufficient Information ◽  
Hematoma Formation ◽  
Risk Of Hemorrhage

SUMMARY:A case of presumed anticoagulant induced hemorrhage into infarction is presented along with a retrospective study of 110 cases of cerebral embolus.An accurate recommendation for the timing of anticoagulation following cerebral embolism hinges on balancing the risk of hemorrhage into infarction against the benefits of early treatment attributed to preventing recurrent embolism. It is felt that the present literature, concepts of pathogenesis and experimental data provide insufficient information to make absolute clinical decisions. The available evidence implies that the risk of further embolic events is three to four times that of hemorrhage into infarction, yet additional randomized prospective studies and better experimental models are needed to establish a valid treatment plan. It may be possible to distinguish separate mechanisms underlying early diffuse hemorrhage into infarction from sudden delayed massive hematoma formation.

scholarly journals A Ragulator–BORC interaction controls lysosome positioning in response to amino acid availability

2017 ◽  
Vol 216 (12) ◽  
pp. 4183-4197 ◽  
Author(s):  
Jing Pu ◽  
Tal Keren-Kaplan ◽  
Juan S. Bonifacino
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cellular Response ◽  
Mammalian Target Of Rapamycin ◽  
Small Gtpase ◽  
Regulatory Effect ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Amino Acid Availability ◽  
Amino Acid Depletion

Lysosomes play key roles in the cellular response to amino acid availability. Depletion of amino acids from the medium turns off a signaling pathway involving the Ragulator complex and the Rag guanosine triphosphatases (GTPases), causing release of the inactive mammalian target of rapamycin complex 1 (mTORC1) serine/threonine kinase from the lysosomal membrane. Decreased phosphorylation of mTORC1 substrates inhibits protein synthesis while activating autophagy. Amino acid depletion also causes clustering of lysosomes in the juxtanuclear area of the cell, but the mechanisms responsible for this phenomenon are poorly understood. Herein we show that Ragulator directly interacts with BLOC-1–related complex (BORC), a multi-subunit complex previously found to promote lysosome dispersal through coupling to the small GTPase Arl8 and the kinesins KIF1B and KIF5B. Interaction with Ragulator exerts a negative regulatory effect on BORC that is independent of mTORC1 activity. Amino acid depletion strengthens this interaction, explaining the redistribution of lysosomes to the juxtanuclear area. These findings thus demonstrate that amino acid availability controls lysosome positioning through Ragulator-dependent, but mTORC1-independent, modulation of BORC.

scholarly journals Determinants of plasma membrane wounding by deforming stress

2010 ◽  
Vol 299 (6) ◽  
pp. L826-L833 ◽  
Author(s):  
Richard A. Oeckler ◽  
Won-Yeon Lee ◽  
Mun-Gi Park ◽  
Othmar Kofler ◽  
Deborah L. Rasmussen ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Optical Tweezers ◽  
Cellular Response ◽  
Ex Vivo ◽  
Experimental Models ◽  
Alveolar Epithelial Cells ◽  
Interfacial Stress ◽  
Alveolar Epithelial ◽  
Adhesive Interactions

Once excess liquid gains access to air spaces of an injured lung, the act of breathing creates and destroys foam and thereby contributes to the wounding of epithelial cells by interfacial stress. Since cells are not elastic continua, but rather complex network structures composed of solid as well as liquid elements, we hypothesize that plasma membrane (PM) wounding is preceded by a phase separation, which results in blebbing. We postulate that interventions such as a hypertonic treatment increase adhesive PM-cytoskeletal (CSK) interactions, thereby preventing blebbing as well as PM wounds. We formed PM tethers in alveolar epithelial cells and fibroblasts and measured their retractive force as readout of PM-CSK adhesive interactions using optical tweezers. A 50-mOsm increase in media osmolarity consistently increased the tether retractive force in epithelial cells but lowered it in fibroblasts. The osmo-response was abolished by pretreatment with latrunculin, cytochalasin D, and calcium chelation. Epithelial cells and fibroblasts were exposed to interfacial stress in a microchannel, and the fraction of wounded cells were measured. Interventions that increased PM-CSK adhesive interactions prevented blebbing and were cytoprotective regardless of cell type. Finally, we exposed ex vivo perfused rat lungs to injurious mechanical ventilation and showed that hypertonic conditioning reduced the number of wounded subpleural alveolus resident cells to baseline levels. Our observations support the hypothesis that PM-CSK adhesive interactions are important determinants of the cellular response to deforming stress and pave the way for preclinical efficacy trials of hypertonic treatment in experimental models of acute lung injury.

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