Abstract 135: MicroRNA 133b Promotes Neural Plasticity Via Exosome Transfer After Treatment Of Stroke With Mesenchymal Stromal Cells In Rats

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
hongqi xin ◽  
Yi Li ◽  
Zhongwu Liu ◽  
Yisheng Cui ◽  
Zheng G Zhang ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Neural Plasticity ◽  
In Vitro Study ◽  
Neural Cells ◽  
Treatment Groups ◽  
Promote Neurite Outgrowth ◽  
Vitro Data ◽  
In Vitro Data

Introduction: Our previous in vitro study demonstrated that MSCs via exosomes transfer miR-133b to neural cells which promote neurite outgrowth. In the present in vivo study, we altered the miR-133b level in MSC exosomes, and tested neural plasticity and functional recovery after MSC treatment of stroke in rats. Methods: We generated stable rat MSC cell lines with transfection of pre-miR-133b (miR-133b+MSC) and miR-133b inhibitor (miR-133b-MSC). Adult Wistar rats were subjected to 2h MCAo and intravenously received MSCs (3x106) or PBS at 24h after MCAo. Functional tests (Neurological Severity Score and Foot Fault) were performed. Rats were sacrificed 14 days after MCAo and adjacent frozen coronal sections were used for immunostaining. Western blot and TaqMan miRNA assay were used to detect protein and miR-133b. Results: The miR-133b levels in MSCs and their corresponding exosomes were increased in miR-133b+MSCs (652.1±54.1% and 367.4±21.6%, respectively), and were decreased in miR-133b-MSCs (33.5±4.4% and 21.0±8.1%, respectively) compared to normal MSCs. At day 14 after MCAo, all MSC treatment groups except miR-133b-MSCs improved (P<0.05) functional recovery compared with PBS treatment, and miR-133b+MSCs improved (P<0.05), while miR-133b-MSCs treatment decreased (P<0.05) functional recovery compared to normal MSCs. Bielshowsky silver, NF-200 and synaptophysin staining showed that neurite remodeling increased along the ischemic boundary zone (P<0.05) after normal MSC treatment and were enhanced by miR-133b+MSC treatment (36.4±4.3%, 12.2±5.2% and 21.6±5.6%, respectively). Compared to MCAo control, normal MSC treatment increased (P<0.05) the miR-133b level in the CSF exosomes, which was further increased by miR-133b+MSCs (101.1±13.2%) and significantly decreased by miR-133b-MSCs (73.9±10.1%). MCAo increased RhoA and CTGF (target proteins of miR-133b, P<0.05, respectively) expression in rat brain and miR-133b+MSC treatment further reversed protein expression at day 14 after MCAo compared to normal MSCs. Conclusions: In concert with our in vitro data, the present study indicates that MSC treatment promotes neural plasticity and functional recovery after stroke by transferring miRNAs (e.g. miR-133b) to neural cells via exosomes.

Use of Toxicokinetics in Risk Assessment Based on In Vitro Data

1993 ◽  
Vol 21 (2) ◽  
pp. 173-180
Author(s):  
Gunnar Johanson
Keyword(s):  
Risk Assessment ◽  
Whole Body ◽  
External Exposure ◽  
Target Dose ◽  
Toxic Response ◽  
Route Of Exposure ◽  
Vitro Data ◽  
In Vitro Data

This presentation addresses some aspects of the methodology, advantages and problems associated with toxicokinetic modelling based on in vitro data. By using toxicokinetic models, particularly physiologically-based ones, it is possible, in principle, to describe whole body toxicokinetics, target doses and toxic effects from in vitro data. Modelling can be divided into three major steps: 1) to relate external exposure (applied dose) of xenobiotic to target dose; 2) to establish the relationship between target dose and effect (in vitro data, e.g. metabolism in microsomes, partitioning in tissue homogenates, and toxicity in cell cultures, are useful in both steps); and 3) to relate external exposure to toxic effect by combining the first two steps. Extrapolations from in vitro to in vivo, between animal and man, and between high and low doses, can easily be carried out by toxicokinetic simulations. In addition, several factors that may affect the toxic response by changing the target dose, such as route of exposure and physical activity, can be studied. New insights concerning the processes involved in toxicity often emerge during the design, refinement and validation of the model. The modelling approach is illustrated by two examples: 1) the carcinogenicity of 1,3-butadiene; and 2) the haematotoxicity of 2-butoxyethanol. Toxicokinetic modelling is an important tool in toxicological risk assessment based on in vitro data. Many factors, some of which can, and should be, studied in vitro, are involved in the expression of toxicity. Successful modelling depends on the identification and quantification of these factors.

scholarly journals MATURATION OF HEMOLYSIN-PRODUCING CELL CLONES

1970 ◽  
Vol 131 (6) ◽  
pp. 1261-1270 ◽  
Author(s):  
George C. Saunders ◽  
Douglas Swartzendruber
Keyword(s):  
Bone Marrow ◽  
Doubling Time ◽  
Sheep Erythrocyte ◽  
Mature Animal ◽  
Cell Clones ◽  
Initial Appearance ◽  
Vitro Data ◽  
In Vitro Data

Cells capable of reacting with sheep erythrocyte (SRBC) antigen to maturate and produce hemolysin appear simultaneously in the bone marrow and spleen of 1-day old Swiss-Webster mice. However, hemolysin-producing cell clones (HPCC) do not result. Complete functional precursor units generally appear in the spleens of mice older than 3 days. In vivo and in vitro data correlate well in this regard. Complete precursor units are not seen in the bone marrow and only very rarely in the thymus. The efficiency of precursor units of neonatal mice when they become functional approximates that of the mature animal when based on the doubling time of plaque-forming cells (PFC). Possible explanations of the initial appearance of incomplete precursor units have been discussed.

scholarly journals Subanesthetic ketamine reactivates adult cortical plasticity to restore vision from amblyopia

2020 ◽  
Author(s):  
Steven F. Grieco ◽  
Xin Qiao ◽  
Xiaoting Zheng ◽  
Yongjun Liu ◽  
Lujia Chen ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Neural Plasticity ◽  
Cortical Plasticity ◽  
Brain Plasticity ◽  
Excitatory Input ◽  
Inhibitory Neurons ◽  
List Type ◽  
Visual Cortical

SummarySubanesthetic ketamine evokes rapid and long-lasting antidepressant effects in human patients. The mechanism for ketamine’s effects remains elusive, but ketamine may broadly modulate brain plasticity processes. We show that single-dose ketamine reactivates adult mouse visual cortical plasticity and promotes functional recovery of visual acuity defects from amblyopia. Ketamine specifically induces down-regulation of neuregulin-1 (NRG1) expression in parvalbumin-expressing (PV) inhibitory neurons in mouse visual cortex. NRG1 downregulation in PV neurons co-tracks both the fast onset and sustained decreases in synaptic inhibition to excitatory neurons, along with reduced synaptic excitation to PV neurons in vitro and in vivo following a single ketamine treatment. These effects are blocked by exogenous NRG1 as well as PV targeted receptor knockout. Thus ketamine reactivation of adult visual cortical plasticity is mediated through rapid and sustained cortical disinhibition via downregulation of PV-specific NRG1 signaling. Our findings reveal the neural plasticity-based mechanism for ketamine-mediated functional recovery from adult amblyopia.Highlights○ Disinhibition of excitatory cells by ketamine occurs in a fast and sustained manner○ Ketamine evokes NRG1 downregulation and excitatory input loss to PV cells○ Ketamine induced plasticity is blocked by exogenous NRG1 or its receptor knockout○ PV inhibitory cells are the initial functional locus underlying ketamine’s effects

Identification of human cytochrome P 450 s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data

2003 ◽  
Vol 59 (5-6) ◽  
pp. 429-442 ◽  
Author(s):  
Xue-Qing Li ◽  
Anders Bj�rkman ◽  
Tommy B. Andersson ◽  
Lars L. Gustafsson ◽  
Collen M. Masimirembwa
Keyword(s):  
Hepatic Clearance ◽  
Human Cytochrome ◽  
Cytochrome P 450 ◽  
Vitro Data ◽  
In Vitro Data

scholarly journals In Vitro Interaction of Caspofungin Acetate with Voriconazole against Clinical Isolates of Aspergillus spp

2002 ◽  
Vol 46 (9) ◽  
pp. 3039-3041 ◽  
Author(s):  
Sofia Perea ◽  
Gloria Gonzalez ◽  
Annette W. Fothergill ◽  
William R. Kirkpatrick ◽  
Michael G. Rinaldi ◽  
...  
Keyword(s):  
Inhibitory Concentration ◽  
Fractional Inhibitory Concentration ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
In Vitro Interaction ◽  
Vitro Data ◽  
In Vitro Data

ABSTRACT The interaction between caspofungin acetate and voriconazole was studied in vitro by using 48 clinical Aspergillus spp. isolates obtained from patients with invasive aspergillosis. MICs were determined by the NCCLS broth microdilution method. Synergy, defined as a fractional inhibitory concentration (FIC) index of <1, was detected in 87.5% of the interactions; an additive effect, defined as an FIC index of 1.0, was observed in 4.2% of the interactions; and a subadditive effect, defined as an FIC index of 1.0 to 2.0, was found in 8.3% of the interactions. No antagonism was observed. Animal models are required to validate the in vivo significance of these in vitro data presented for the combination of caspofungin and voriconazole.

scholarly journals How well can in vitro data predict in vivo effects of chemicals? Rodent carcinogenicity as a case study

2016 ◽  
Vol 77 ◽  
pp. 54-64 ◽  
Author(s):  
Louis Anthony (Tony) Cox ◽  
Douglas A. Popken ◽  
A. Michael Kaplan ◽  
Laura M. Plunkett ◽  
Richard A. Becker
Keyword(s):  
In Vivo Effects ◽  
Vitro Data ◽  
In Vitro Data ◽  
Rodent Carcinogenicity

scholarly journals Functional inhibition of osteoblastic cells in an in vivo mouse model of myeloid leukemia

Blood ◽  
2012 ◽  
Vol 119 (2) ◽  
pp. 540-550 ◽  
Author(s):  
Benjamin J. Frisch ◽  
John M. Ashton ◽  
Lianping Xing ◽  
Michael W. Becker ◽  
Craig T. Jordan ◽  
...  
Keyword(s):  
Bone Loss ◽  
Myeloid Leukemia ◽  
Serum Levels ◽  
Osteoblastic Cells ◽  
Novel Approach ◽  
Vitro Data ◽  
In Vitro Data ◽  
Marrow Cells

Pancytopenia is a major cause of morbidity in acute myeloid leukemia (AML), yet its cause is unclear. Normal osteoblastic cells have been shown to support hematopoiesis. To define the effects of leukemia on osteoblastic cells, we used an immunocompetent murine model of AML. Leukemic mice had inhibition of osteoblastic cells, with decreased serum levels of the bone formation marker osteocalcin. Osteoprogenitor cells and endosteal-lining osteopontin+ cells were reduced, and osteocalcin mRNA in CD45− marrow cells was diminished. This resulted in severe loss of mineralized bone. Osteoclasts were only transiently increased without significant increases in bone resorption, and their inhibition only partially rescued leukemia-induced bone loss. In vitro data suggested that a leukemia-derived secreted factor inhibited osteoblastic cells. Because the chemokine CCL-3 was recently reported to inhibit osteoblastic function in myeloma, we tested its expression in our model and in AML patients. Consistent with its potential novel role in leukemic-dependent bone loss, CCL-3 mRNA was significantly increased in malignant marrow cells from leukemic mice and from samples from AML patients. Based on these results, we propose that therapeutic mitigation of leukemia-induced uncoupling of osteoblastic and osteoclastic cells may represent a novel approach to promote normal hematopoiesis in patients with myeloid neoplasms.

scholarly journals Use of Terbinafine in Mouse and Rat Models of Pneumocystis carinii Pneumonia

2002 ◽  
Vol 46 (2) ◽  
pp. 514-516 ◽  
Author(s):  
Peter D. Walzer ◽  
Alan Ashbaugh
Keyword(s):  
Pneumocystis Carinii Pneumonia ◽  
Drug Testing ◽  
Inhibitory Concentration ◽  
Pneumocystis Carinii ◽  
Rat Models ◽  
Vitro Data ◽  
In Vitro Data

ABSTRACT Terbinafine, an allylamine used to treat onychomycosis, has been reported to be active against rat Pneumocystis carinii in vitro and in vivo. By contrast, our in vitro data showed that the 50% inhibitory concentration of terbinafine against rat P. carinii is 3.7 μg/ml, a level that cannot be clinically achieved in serum. In the present study, terbinafine administered orally at doses of 20 to 400 mg/kg/day and 50 to 250 mg/kg/day was ineffective therapy for mouse and rat models of pneumocystosis, respectively. These results emphasize the complexities of P. carinii drug testing and the need for caution before considering studies in humans.

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