Search Results (6)

The present study investigates the possible use of manganese (Mn)-based liposomal formulations for diagnostic applications in imaging techniques such as magnetic resonance imaging (MRI), with the aim of overcoming the toxicity limitations associated with the use of free Mn²⁺. Specifically, anionic liposomes carrying two model Mn(II)-based compounds, MnCl₂ (MC) and Mn(HMTA) (MH), were prepared and characterised in terms of morphology, size, loading capacity, and in vitro activity. Homogeneous dispersions characterised mainly by unilamellar vesicles were obtained; furthermore, no differences in size and morphology were detected between unloaded and Mn-loaded vesicles. The encapsulation efficiency of MC and MH was evaluated on extruded liposomes by means of ICP-OES analysis. The obtained results showed that both MC and MH are almost completely retained by the lipid portion of liposomes (LPs), with encapsulation efficiencies of 99.7% for MC and 98.8% for MH. The magnetic imaging properties of the produced liposomal formulations were investigated for application in a potential preclinical scenario by collecting magnetic resonance images of a phantom designed to compare the paramagnetic contrast properties of free MC and MH compounds and the corresponding manganese-containing liposome dispersions. It was found that both LP-MC and LP-MH at low concentrations (0.5 mM) show better contrast (contrast-to-noise ratios of 194 and 209, respectively) than solutions containing free Mn at the same concentrations (117 and 134, respectively) and are safe to use on human cells at the selected dose. Taken together, the results of this comparative analysis suggest that these liposome-containing Mn compounds might be suitable for diagnostic purposes. Full article

Anesthesia is often used in preclinical imaging studies that incorporate mouse or rat models. However, multiple reports indicate that anesthesia has significant physiological impacts. Thus, there has been great interest in performing imaging studies in awake, unanesthetized animals to obtain accurate results without the confounding physiological effects of anesthesia. Here, we describe a newly designed mouse holder that is interfaceable with existing MRI systems and enables awake in vivo mouse imaging. This holder significantly reduces head movement of the awake animal compared to previously designed holders and allows for the acquisition of improved anatomical images. In addition to applications in anatomical T₂-weighted magnetic resonance imaging (MRI), we also describe applications in acquiring ³¹P spectra, manganese-enhanced magnetic resonance imaging (MEMRI) transport rates and resting-state functional magnetic resonance imaging (rs-fMRI) in awake animals and describe a successful conditioning paradigm for awake imaging. These data demonstrate significant differences in ³¹P spectra, MEMRI transport rates, and rs-fMRI connectivity between anesthetized and awake animals, emphasizing the importance of performing functional studies in unanesthetized animals. Furthermore, these studies demonstrate that the mouse holder presented here is easy to construct and use, compatible with standard Bruker systems for mouse imaging, and provides rigorous results in awake mice. Full article

Cervical spinal cord injury (SCI) remains a devastating event without adequate treatment options despite decades of research. In this context, the usefulness of common preclinical SCI models has been criticized. We, therefore, aimed to use a clinically relevant animal model of severe cervical SCI to assess the long-term effects of neural precursor cell (NPC) transplantation on secondary injury processes and functional recovery. To this end, we performed a clip contusion-compression injury at the C6 level in 40 female Wistar rats and a sham surgery in 10 female Wistar rats. NPCs, isolated from the subventricular zone of green fluorescent protein (GFP) expressing transgenic rat embryos, were transplanted ten days after the injury. Functional recovery was assessed weekly, and FluoroGold (FG) retrograde fiber-labeling, as well as manganese-enhanced magnetic resonance imaging (MEMRI), were performed prior to the sacrifice of the animals eight weeks after SCI. After cryosectioning of the spinal cords, immunofluorescence staining was conducted. Results were compared between the treatment groups (NPC, Vehicle, Sham) and statistically analyzed (p < 0.05 was considered significant). Despite the severity of the injury, leading to substantial morbidity and mortality during the experiment, long-term survival of the engrafted NPCs with a predominant differentiation into oligodendrocytes could be observed after eight weeks. While myelination of the injured spinal cord was not significantly improved, NPC treated animals showed a significant increase of intact perilesional motor neurons and preserved spinal tracts compared to untreated Vehicle animals. These findings were associated with enhanced preservation of intact spinal cord tissue. However, reactive astrogliosis and inflammation where not significantly reduced by the NPC-treatment. While differences in the Basso–Beattie–Bresnahan (BBB) score and the Gridwalk test remained insignificant, animals in the NPC group performed significantly better in the more objective CatWalk XT gait analysis, suggesting some beneficial effects of the engrafted NPCs on the functional recovery after severe cervical SCI. Full article

Tauopathies are a group of more than twenty known disorders that involve progressive neurodegeneration, cognitive decline and pathological tau accumulation. Current therapeutic strategies provide only limited, late-stage symptomatic treatment. This is partly due to lack of understanding of the molecular mechanisms linking tau and cellular dysfunction, especially during the early stages of disease progression. In this study, we treated early stage tau transgenic mice with a multi-target kinase inhibitor to identify novel substrates that contribute to cognitive impairment and exhibit therapeutic potential. Drug treatment significantly ameliorated brain atrophy and cognitive function as determined by behavioral testing and a sensitive imaging technique called manganese-enhanced magnetic resonance imaging (MEMRI) with quantitative R1 mapping. Surprisingly, these benefits occurred despite unchanged hyperphosphorylated tau levels. To elucidate the mechanism behind these improved cognitive outcomes, we performed quantitative proteomics to determine the altered protein network during this early stage in tauopathy and compare this model with the human Alzheimer’s disease (AD) proteome. We identified a cluster of preserved pathways shared with human tauopathy with striking potential for broad multi-target kinase intervention. We further report high confidence candidate proteins as novel therapeutically relevant targets for the treatment of tauopathy. Proteomics data are available via ProteomeXchange with identifier PXD023562. Full article

In order to simulate a circuit by applying various logic circuits and full chip using the HSPICE model, which can consider electrical coupling proposed in the previous research, it is investigated whether additional electrical coupling other than electrical coupling by top and bottom layer exists. Additional electrical coupling were verified through device simulation and confirmed to be blocked by heavily doped source/drain. Comparing the HSPICE circuit simulation results using the newly proposed monolithic 3D NAND (M3DNAND) structure in the technology computer-aided design (TCAD) mixed-mode and monolithic 3D inverter (M3DINV) unit cell model was once more verified. It is possible to simulate various logic circuits using the previously proposed M3DINV unit cell model. We simulated the operation and performances of M3DNAND, M3DNOR, 2 × 1 multiplexer (MUX), D flip-flop (D-FF), and static random access memry (SRAM). Full article

Here, we investigated the diagnostic performance of manganese (Mn)-enhanced magnetic resonance imaging (MEMRI) in colorectal cancer (CRC). The ability of CRC cell lines SW620 and SW480 to uptake Mn was evaluated and compared with a normal colon cell using MEMRI. Subcutaneous xenografts in nude mice underwent MRI examination at tumor sizes of 5, 10, and 15 mm. Contrast enhancement was compared between gadolinium (Gd)- and Mn-enhanced MRI. SW620 and SW480 cell lines took up more Mn²⁺ than normal cells, resulting in 4.5 and 2 times greater T1 value shortening than normal cell using in vitro MEMRI (P < 0.001). Most xenografts (17/23) enhanced markedly on MEMRI. A heterogeneous enhancement pattern invariably noted whether Mn or Gd agents were administered, but tumors imaged using MEMRI showed a greater degree of enhancement with a larger extent of enhanced area than those imaged using Gd-enhanced MRI. The numbers of markedly Mn-enhanced cases were more in the 5-mm-size tumor group than in 10- or 15-mm-size tumor groups. Overall, MEMRI could enhance CRCs and it showed potential in detecting early small lesions and markedly enhancing tumors that had minimal Gd enhancement. Full article