Perinatal hypoxia is a major cause of neurodevelopmental deficits. Neuronal migration patterns are particularly sensitive to perinatal hypoxia/ischemia and are associated with the clinical deficits. The rat model of hypoxia/ischemia at P7 mimics that of perinatal injury in humans. Before assessing the effects of postnatal injury on brain development, it is essential to determine the normal developmental trajectories of various brain structures in individual animals. In vivo longitudinal diffusion tensor imaging (DTI) was performed from postnatal day 0 (P0) to P56 on Wistar rats. The DTI metrics, mean diffusivity (MD), fractional anisotropy (FA), axial (lambdal) and radial (lambdat) diffusivities, were determined for four gray matter and eight white matter structures. The FA of the cortical plate and the body of corpus callosum decreased significantly during the first 3 weeks after birth. The decrease in the cortical plate's FA value was associated mainly with an increase in lambdat. The initial decrease in FA of corpus callosum was associated with a significant decrease in lambdal. The FA of corpus callosum increased during the rest of the observational period, which was mainly associated with a decrease in lambdat. The FA of gray matter structures, hippocampus, caudate putamen, and cortical mantle did not show significant changes between P0 and P56. In contrast, the majority of white matter structures showed significant changes between P0 and P56. These temporal changes in the DTI metrics were related to the neuronal and axonal pruning and myelination that are known to occur in the developing brain.

A plethora of magnetic nanoparticles has been developed and investigated under different alternating magnetic fields (AMF) for the hyperthermic treatment of malignant tissues. Yet, clinical applications of magnetic hyperthermia are sporadic, mostly due to the low energy conversion efficiency of the metallic nanoparticles and the high tissue concentrations required. Here, we study the hyperthermic performance of commercially available formulations of superparamagnetic iron oxide nanoparticles (SPIOs), with core diameter of 5, 7 and 14 nm, in terms of absolute temperature increase ΔT and specific absorption rate (SAR). These nanoparticles are operated under a broad range of AMF conditions, with frequency f varying between 0.2 and 30 MHz; field strength H ranging from 4 to 10 kA m−1; and concentration cMNP varying from 0.02 to 3.5 mg ml−1. At high frequency field (∼30 MHz), non specific heating dominates and ΔT correlates with the electrical conductivity of the medium. At low frequency field (<1 MHz), non specific heating is negligible and the relaxation of the SPIO within the AMF is the sole energy source. We show that the ΔT of the medium grows linearly with cMNP, whereas the SARMNP of the magnetic nanoparticles is independent of cMNP and varies linearly with f and H2. Using a computational model for heat transport in a biological tissue, the minimum requirements for local hyperthermia (Ttissue >42°C) and thermal ablation (Ttissue >50°C) are derived in terms of cMNP, operating AMF conditions and blood perfusion. The resulting maps can be used to rationally design hyperthermic treatments and identifying the proper route of administration – systemic versus intratumor injection – depending on the magnetic and biodistribution properties of the nanoparticles.

Macrophages play a crucial role in regeneration and consecutive phases of wound healing. In this review, we summarise current knowledge on the ontogeny, origin, phenotypical heterogeneity, and functional exchangeability of macrophages participating in these processes. We also describe the genetic, pharmacologic, and bioengineering methods for manipulation of macrophage phenotype and functions and their potential for development of the novel, clinically applicable therapies.

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Macrophages play a crucial role in homeostasis, regeneration, and innate and adaptive immune responses. Functionally different macrophages have different shapes and molecular phenotypes that depend on the actin cytoskeleton, which is regulated by the small GTPase RhoA. The naive M0 macrophages are slightly elongated, proinflammatory M1 are round, and M2 antiinflammatory macrophages are elongated. We have recently shown in the rodent model system that genetic or pharmacologic interference with the RhoA pathway deregulates the macrophage actin cytoskeleton, causes extreme macrophage elongation, and prevents macrophage migration. Here, we report that an exposure of macrophages to a nonuniform magnetic field causes extreme elongation of macrophages and has a profound effect on their molecular components and organelles. Using immunostaining and Western blotting, we observed that magnetic force rearranges the macrophage actin cytoskeleton, the Golgi complex, and the cation channel receptor TRPM2, and modifies the expression of macrophage molecular markers. We have found that the magnetic-field-induced alterations are very similar to changes caused by RhoA interference. We also analyzed magnetic-field-induced forces acting on macrophages and found that the location and alignment of magnetic-field-elongated macrophages correlate very well with the simulated distribution and orientation of such magnetic force lines.

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