Importance of alignment between local DC magnetic field and an oscillating magnetic field in responses of brain tissue in vitro and in vivo

1990 ◽  
Vol 11 (2) ◽  
pp. 159-167 ◽  
Author(s):  
C. F. Blackman ◽  
S. G. Benane ◽  
D. E. House ◽  
D. J. Elliott
Keyword(s):  
Magnetic Field ◽  
Brain Tissue ◽  
Dc Magnetic Field ◽  
Oscillating Magnetic Field

Monocytes as Carriers of Magnetic Nanoparticles for Tracking Inflammation in the Epileptic Rat Brain

2019 ◽  
Vol 16 (7) ◽  
pp. 637-644 ◽  
Author(s):  
Hadas Han ◽  
Sara Eyal ◽  
Emma Portnoy ◽  
Aniv Mann ◽  
Miriam Shmuel ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Ex Vivo ◽  
In Vivo Studies ◽  
Nanoparticle Distribution ◽  
Spontaneous Seizures ◽  
Systemic Distribution ◽  
Hippocampal Ca1 ◽  
Pilocarpine Model

Background: Inflammation is a hallmark of epileptogenic brain tissue. Previously, we have shown that inflammation in epilepsy can be delineated using systemically-injected fluorescent and magnetite- laden nanoparticles. Suggested mechanisms included distribution of free nanoparticles across a compromised blood-brain barrier or their transfer by monocytes that infiltrate the epileptic brain. Objective: In the current study, we evaluated monocytes as vehicles that deliver nanoparticles into the epileptic brain. We also assessed the effect of epilepsy on the systemic distribution of nanoparticleloaded monocytes. Methods: The in vitro uptake of 300-nm nanoparticles labeled with magnetite and BODIPY (for optical imaging) was evaluated using rat monocytes and fluorescence detection. For in vivo studies we used the rat lithium-pilocarpine model of temporal lobe epilepsy. In vivo nanoparticle distribution was evaluated using immunohistochemistry. Results: 89% of nanoparticle loading into rat monocytes was accomplished within 8 hours, enabling overnight nanoparticle loading ex vivo. The dose-normalized distribution of nanoparticle-loaded monocytes into the hippocampal CA1 and dentate gyrus of rats with spontaneous seizures was 176-fold and 380-fold higher compared to the free nanoparticles (p<0.05). Seizures were associated with greater nanoparticle accumulation within the liver and the spleen (p<0.05). Conclusion: Nanoparticle-loaded monocytes are attracted to epileptogenic brain tissue and may be used for labeling or targeting it, while significantly reducing the systemic dose of potentially toxic compounds. The effect of seizures on monocyte biodistribution should be further explored to better understand the systemic effects of epilepsy.

scholarly journals Magnetic Nanodiscs—A New Promising Tool for Microsurgery of Malignant Neoplasms

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1459
Author(s):  
Tatiana N. Zamay ◽  
Vladimir S. Prokopenko ◽  
Sergey S. Zamay ◽  
Kirill A. Lukyanenko ◽  
Olga S. Kolovskaya ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Remote Control ◽  
Tumor Cells ◽  
Biological Effects ◽  
Malignant Neoplasms ◽  
Rotating Magnetic Fields ◽  
Magnetic Structures ◽  
Promising Tool

Magnetomechanical therapy is one of the most perspective directions in tumor microsurgery. According to the analysis of recent publications, it can be concluded that a nanoscalpel could become an instrument sufficient for cancer microsurgery. It should possess the following properties: (1) nano- or microsized; (2) affinity and specificity to the targets on tumor cells; (3) remote control. This nano- or microscalpel should include at least two components: (1) a physical nanostructure (particle, disc, plates) with the ability to transform the magnetic moment to mechanical torque; (2) a ligand—a molecule (antibody, aptamer, etc.) allowing the scalpel precisely target tumor cells. Literature analysis revealed that the most suitable nanoscalpel structures are anisotropic, magnetic micro- or nanodiscs with high-saturation magnetization and the absence of remanence, facilitating scalpel remote control via the magnetic field. Additionally, anisotropy enhances the transmigration of the discs to the tumor. To date, four types of magnetic microdiscs have been used for tumor destruction: synthetic antiferromagnetic P-SAF (perpendicular) and SAF (in-plane), vortex Py, and three-layer non-magnetic–ferromagnet–non-magnetic systems with flat quasi-dipole magnetic structures. In the current review, we discuss the biological effects of magnetic discs, the mechanisms of action, and the toxicity in alternating or rotating magnetic fields in vitro and in vivo. Based on the experimental data presented in the literature, we conclude that the targeted and remotely controlled magnetic field nanoscalpel is an effective and safe instrument for cancer therapy or theranostics.

scholarly journals In Vivo and In Vitro Toxicodynamic Analyses of New Quinolone-and Nonsteroidal Anti-Inflammatory Drug-Induced Effects on the Central Nervous System

1999 ◽  
Vol 43 (5) ◽  
pp. 1091-1097 ◽  
Author(s):  
Hideki Kita ◽  
Hirotami Matsuo ◽  
Hitomi Takanaga ◽  
Junichi Kawakami ◽  
Koujirou Yamamoto ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Threshold Concentration ◽  
Current Response ◽  
Drug Induced ◽  
Inhibition Ratio ◽  
New Quinolones ◽  
The Central Nervous System ◽  
Anti Inflammatory

ABSTRACT We investigated the correlation between an in vivo isobologram based on the concentrations of new quinolones (NQs) in brain tissue and the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) for the occurrence of convulsions in mice and an in vitro isobologram based on the concentrations of both drugs for changes in the γ-aminobutyric acid (GABA)-induced current response in Xenopus oocytes injected with mRNA from mouse brains in the presence of NQs and/or NSAIDs. After the administration of enoxacin (ENX) in the presence or absence of felbinac (FLB), ketoprofen (KTP), or flurbiprofen (FRP), a synergistic effect was observed in the isobologram based on the threshold concentration in brain tissue between mice with convulsions and those without convulsions. The three NSAIDs did not affect the pharmacokinetic behavior of ENX in the brain. However, the ENX-induced inhibition of the GABA response in the GABAA receptor expressed in Xenopus oocytes was enhanced in the presence of the three NSAIDs. The inhibition ratio profiles of the GABA responses for both drugs were analyzed with a newly developed toxicodynamic model. The inhibitory profiles for ENX in the presence of NSAIDs followed the order KTP (1.2 μM) > FRP (0.3 μM) > FLB (0.2 μM). These were 50- to 280-fold smaller than those observed in the absence of NSAIDs. The inhibition ratio (0.01 to 0.02) of the GABAA receptor in the presence of both drugs was well-fitted to the isobologram based on threshold concentrations of both drugs in brain tissue between mice with convulsions and those without convulsions, despite the presence of NSAIDs. In mice with convulsions, the inhibitory profiles of the threshold concentrations of both drugs in brain tissue of mice with convulsions and those without convulsions can be predicted quantitatively by using in vitro GABA response data and toxicodynamic model.

Development of an In Vitro 3D Brain Tissue Model Mimicking In Vivo-Like Pro-inflammatory and Pro-oxidative Responses

2018 ◽  
Vol 46 (6) ◽  
pp. 877-887 ◽  
Author(s):  
Hyung Joon Cho ◽  
Scott S. Verbridge ◽  
Rafael V. Davalos ◽  
Yong W. Lee
Keyword(s):  
Brain Tissue ◽  
Tissue Model ◽  
Oxidative Responses

scholarly journals In VitroandIn VivoEvaluation of APX001A/APX001 and Other Gwt1 Inhibitors againstCryptococcus

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Karen Joy Shaw ◽  
Wiley A. Schell ◽  
Jonathan Covel ◽  
Gisele Duboc ◽  
C. Giamberardino ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Lung Tissue ◽  
Fungal Infections ◽  
Treatment Options ◽  
Content Type ◽  
Fungal Burden ◽  
Geographical Regions ◽  
Current Therapies

ABSTRACTCryptococcal meningitis (CM), caused primarily byCryptococcus neoformans, is uniformly fatal if not treated. Treatment options are limited, especially in resource-poor geographical regions, and mortality rates remain high despite current therapies. Here we evaluated thein vitroandin vivoactivity of several compounds, including APX001A and its prodrug, APX001, currently in clinical development for the treatment of invasive fungal infections. These compounds target the conserved Gwt1 enzyme that is required for the localization of glycosylphosphatidylinositol (GPI)-anchored cell wall mannoproteins in fungi. The Gwt1 inhibitors had low MIC values, ranging from 0.004 μg/ml to 0.5 μg/ml, against bothC. neoformansandC. gattii. APX001A and APX2020 demonstratedin vitrosynergy with fluconazole (fractional inhibitory concentration index, 0.37 for both). In a CM model, APX001 and fluconazole each alone reduced the fungal burden in brain tissue (0.78 and 1.04 log10CFU/g, respectively), whereas the combination resulted in a reduction of 3.52 log10CFU/g brain tissue. Efficacy, as measured by a reduction in the brain and lung tissue fungal burden, was also observed for another Gwt1 inhibitor prodrug, APX2096, where dose-dependent reductions in the fungal burden ranged from 5.91 to 1.79 log10CFU/g lung tissue and from 7.00 and 0.92 log10CFU/g brain tissue, representing the nearly complete or complete sterilization of lung and brain tissue at the higher doses. These data support the further clinical evaluation of this new class of antifungal agents for the treatment of CM.

scholarly journals Embedded axonal fiber tracts improve finite element model predictions of traumatic brain injury

2019 ◽  
Vol 19 (3) ◽  
pp. 1109-1130 ◽  
Author(s):  
Marzieh Hajiaghamemar ◽  
Taotao Wu ◽  
Matthew B. Panzer ◽  
Susan S. Margulies
Keyword(s):  
Traumatic Brain Injury ◽  
Finite Element ◽  
Brain Injury ◽  
Strain Rate ◽  
Brain Tissue ◽  
Brain Injuries ◽  
Characteristic Curve ◽  
Strain And Strain Rate

AbstractWith the growing rate of traumatic brain injury (TBI), there is an increasing interest in validated tools to predict and prevent brain injuries. Finite element models (FEM) are valuable tools to estimate tissue responses, predict probability of TBI, and guide the development of safety equipment. In this study, we developed and validated an anisotropic pig brain multi-scale FEM by explicitly embedding the axonal tract structures and utilized the model to simulate experimental TBI in piglets undergoing dynamic head rotations. Binary logistic regression, survival analysis with Weibull distribution, and receiver operating characteristic curve analysis, coupled with repeated k-fold cross-validation technique, were used to examine 12 FEM-derived metrics related to axonal/brain tissue strain and strain rate for predicting the presence or absence of traumatic axonal injury (TAI). All 12 metrics performed well in predicting of TAI with prediction accuracy rate of 73–90%. The axonal-based metrics outperformed their rival brain tissue-based metrics in predicting TAI. The best predictors of TAI were maximum axonal strain times strain rate (MASxSR) and its corresponding optimal fraction-based metric (AF-MASxSR7.5) that represents the fraction of axonal fibers exceeding MASxSR of 7.5 s−1. The thresholds compare favorably with tissue tolerances found in in–vitro/in–vivo measurements in the literature. In addition, the damaged volume fractions (DVF) predicted using the axonal-based metrics, especially MASxSR (DVF = 0.05–4.5%), were closer to the actual DVF obtained from histopathology (AIV = 0.02–1.65%) in comparison with the DVF predicted using the brain-related metrics (DVF = 0.11–41.2%). The methods and the results from this study can be used to improve model prediction of TBI in humans.

Development and Test of an Extendable Endoprosthesis for Bone Reconstruction in the Leg

1994 ◽  
Vol 17 (3) ◽  
pp. 155-162 ◽  
Author(s):  
G.J. Verkerke ◽  
H. Schraffordt Koops ◽  
R.P.H. Veth ◽  
H.J. Grootenboer ◽  
L.J. De Boer ◽  
...  
Keyword(s):  
Magnetic Field ◽  
External Magnetic Field ◽  
Growth Plate ◽  
Animal Experiments ◽  
Bone Tumour ◽  
In Vitro Tests ◽  
Bone Reconstruction ◽  
Malignant Bone Tumour

A malignant bone tumour may develop in the femur of a child. In the majority of cases it will be necessary to resect the bone involved, growth plate and adjacent tissues. A modular endoprosthetic system has been developed which can be extended non-invasively to bridge the defect resulting from such a resection. Elongation is achieved by using an external magnetic field. In vitro tests with a prototype showed that the lengthening element met all requirements. Six animal experiments showed that the lengthening element also functioned in vivo.

scholarly journals Genomics Analysis of Metabolic Pathways of Human Stem Cell-Derived Microglia-Like Cells and the Integrated Cortical Spheroids

2019 ◽  
Vol 2019 ◽  
pp. 1-21 ◽  
Author(s):  
Julie Bejoy ◽  
Xuegang Yuan ◽  
Liqing Song ◽  
Thien Hua ◽  
Richard Jeske ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Metabolic Pathways ◽  
Disease Modeling ◽  
Aerobic Glycolysis ◽  
Three Dimensional ◽  
Initiation Factor ◽  
Human Brain Tissue ◽  
P53 Signaling

Brain spheroids or organoids derived from human pluripotent stem cells (hiPSCs) are still not capable of completely recapitulating in vivo human brain tissue, and one of the limitations is lack of microglia. To add built-in immune function, coculture of the dorsal forebrain spheroids with isogenic microglia-like cells (D-MG) was performed in our study. The three-dimensional D-MG spheroids were analyzed for their transcriptome and compared with isogenic microglia-like cells (MG). Cortical spheroids containing microglia-like cells displayed different metabolic programming, which may affect the associated phenotype. The expression of genes related to glycolysis and hypoxia signaling was increased in cocultured D-MG spheroids, indicating the metabolic shift to aerobic glycolysis, which is in favor of M1 polarization of microglia-like cells. In addition, the metabolic pathways and the signaling pathways involved in cell proliferation, cell death, PIK3/AKT/mTOR signaling, eukaryotic initiation factor 2 pathway, and Wnt and Notch pathways were analyzed. The results demonstrate the activation of mTOR and p53 signaling, increased expression of Notch ligands, and the repression of NF-κB and canonical Wnt pathways, as well as the lower expression of cell cycle genes in the cocultured D-MG spheroids. This analysis indicates that physiological 3-D microenvironment may reshape the immunity of in vitro cortical spheroids and better recapitulate in vivo brain tissue function for disease modeling and drug screening.

Magic-TT (Magnetism-induced cell target transplantation) Enhanced the CD45+ Cells Target Migration, in Situ Proliferation and Promotion of Hematopoietic Recovery after Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5404-5404
Author(s):  
Qianli Jiang ◽  
Hao Huang ◽  
Yongjun Zhou ◽  
Qiuxia Zhang ◽  
Sun Xiaowei ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Bone Marrow ◽  
Stem Cell ◽  
Cell Transplantation ◽  
In Vitro Study ◽  
Confocal Microscope ◽  
Hematopoietic Recovery ◽  
Donor Cells

Abstract Background: In our previous work (56th ASH poster, No.2416), we developed a novel cell transplantation system named MagIC-TT. The purpose of this study is to explore whether the MagIC-TT can promote hematopoietic recovery in the mice experiment and illustrate it¡¯s mechanism both in vivo and in vitro. Methods: 1) In vivo study: With regard to auto-transplantation, the C57BL/6 CD45-GFP cells were sorted and magnetized from the bone marrow of C57BL/6-Tg(CAG-EGFP) mice. Forty C57BL/6 female mice (2 groups, twenty mice each group) were transplanted into the femur cavity with or without magnetic field (M or W group), after 7.5Gy irradiation. Following transplantation, the survival of mice, hematopoiesis as well as GFP+ cells in different tissues, such as peripheral blood, bone marrow, liver, spleen, thymus and lung etc. were observed. Femurs of recipients were decalcified with our own derived semi-solid decalcification (SSD) technique to illustrate the distribution, proliferation of donor cells and the relationship between recipients and donor cells. Allo-transplantation: The C57BL/6 CD45-GFP cells were injected into the femur cavity of FVB mRFP transgenic mice (sponsored by Prof. XH Wu, Fudan University, Shanghai, China) after 7.5Gy irradiation. GVHD was observed in addition to what was done in auto-transplantation. 2) In vitro study: Magnetized CD45-GFP cells and non-magnetized BMSC-RFPs were cultured respectively or co-cultured with or without magnetic field (M or W group). The magnetic field was added to the top or the bottom of cell culture dish. Cell morphology, cell proliferation, cell viability, as well as cell migration, transwell migration and matrigel migration assays induced by magnetism were studied. The interaction of CD45-GFP cells and BMSC-RFPs was observed by confocal microscope, electronic microscope, immunohistochemical staining, western blot, real-time PCR and deep sequencing. Results: 1) In vivo study: During the first few hours after transplantation, lots of magnetized CD45-GFP cells resided within the femur and knee joints in M group while few in W group. Many GFP cells migrated into the lung soon after transplantation in the W group (P =0.046), followed by other organs such as kidney and skin (Fig.1). FACS showed that more GFP+ cells resided within the target femurs than the controls (Table.1). With SSD, frozen sections, confocal microscope and Lightsheet Z.1 Microimage (Carl Zeiss); transplanted GFP+ cells and their micro-environment were all well demonstrated (Fig.1). On removal of magnetic field, CD45-GFP cells were observed to migrate into the spleen, kidney, gut and other organs, showing the slow release of target transplanted cells from femur. GVHD on skin and lung etc. were observed in C57BL/6 to FVB allogenic transplanted mice (Fig. 1). The hematopoietic recovery in M group occurs much earlier than the controls, especially for the platelets, 10.67d ¡À 1.53d vs 14.75d ¡À 2.06d (M vs W group, P =0.035). 2) In vitro study: With the help of MagIC-TT, CD45-GFP cells can migrate through the matrigel and transwell membranes much more efficiently. The magnetized CD45-GFP cells advance toward the inner roof of petri dish in the culture medium, and attach to BMSC-RFP growing on the inner roof of dish and proliferate in the niche composed by BMSC-RFP under the effect of magnetic field (Fig.2). Conclusion: MagIC-TT could enhance CD45+ cells target migration, improve stem cell homing and proliferation efficiency, as well as promotion hematopoietic recovery in vivo. This study would shed light on current Hematological Stem Cell Transplantation (HSCT) and other cell therapies. Table 1. The FACS results of femurs of CD45-GFP cells injected into C57 mice, at 0.5h, 24h and 72h respectively. group 0.5h£¨%£© p 24h£¨%£© p 72h£¨%£© p *LC **RT *LC **RT *LC **RT BMM 0.017¡À0.006 0.497¡À0.151 0.040 0.080¡À0.026 1.573¡À0.508 0.030 0.190¡À0.139 1.960¡À0.809 0.049 BMW 0.017¡À0.012 0.050¡À0.017 0.184 0.013¡À0.006 0.027¡À0.015 0.184 0.023¡À0.015 0.320¡À0.434 0.368 P 1.000 0.007 0.013 0.006 0.108 0.036 *LC: Control femur without magnetic field (W group); **RT: Treated femur with magnetic field (M group). Disclosures No relevant conflicts of interest to declare.

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