Poly(vinyl alcohol)/sodium alginate/magnetite composites: magnetic force microscopy for tracking magnetic domains.

Hydrogels of poly(vinyl alcohol) (PVA)/sodium alginate (SA), and magnetic nanoparticles (MNPs) were prepared by solvent casting in the absence and in the presence of magnets, in order to obtain MNPs distributed randomly (PVA/SA-rMNP) and magnetically oriented MNPs (PVA/SA-gMNP) in the polymer matrix. Atomic force microscopy (AFM) and magnetic force microscopy (MFM) techniques were used to evaluate the topography and to map the distribution of magnetic domains in the polymer matrix, respectively. The tip-surface distance (lift distance) of 50 nm during the MFM analyses facilitated the mapping of magnetic domains because the van der Waals forces were minimized. The magnetic signal stemming from clusters of MNPs were more easily identified than that from isolated MNPs. PVA and SA, PVA/SA, PVA/SA-rMNP, and PVA/SA-gMNP coatings with surface roughness (Ra) values of 3.8 nm, 28.7 nm, and 49.8 nm, respectively, were tested for the proliferation of mouse hippocampal HT-22 cells. While PVA/SA, PVA/SA-rMNP, and PVA/SA-gMNP coatings preserved cell viability >70% in comparison to the control (plastic plate) over 48 h, cell proliferation tended to decrease on surfaces with higher Ra values (PVA/SA-gMNP). These findings showed that the orientation of magnetic domains led to an increase of surface roughness, which decreased the viability of HT-22 cells. Thus, these results might be interesting for situations, where the control of cell proliferation is necessary.

Static Magnetic Field Reduces Intracellular ROS Levels and Protects Cells Against Peroxide-Induced Damage: Suggested Roles for Catalase.

A feature in neurodegenerative disorders is the loss of neurons, caused by several factors including oxidative stress induced by reactive oxygen species (ROS). In this work, static magnetic field (SMF) was applied in vitro to evaluate its effect on the viability, proliferation, and migration of human neuroblastoma SH-SY5Y cells, and on the toxicity induced by hydrogen peroxide (H2O2), tert-butyl hydroperoxide (tBHP), H2O2/sodium azide (NaN3) and photosensitized oxidations by photodynamic therapy (PDT) photosensitizers. The SMF increased almost twofold the cell expression of the proliferation biomarker Ki-67 compared to control cells after 7 days of exposure. Exposure to SMF accelerated the wound healing of scratched cell monolayers and significantly reduced the H2O2-induced and the tBHP-induced cell deaths. Interestingly, SMF was able to revert the effects of NaN3 (a catalase inhibitor), suggesting an increased activity of catalase under the influence of the magnetic field. In agreement with this hypothesis, SMF significantly reduced the oxidation of DCF-H2, indicating a lower level of intracellular ROS. When the redox imbalance was triggered through photosensitized oxidation, no protection was observed. This observation aligns with the proposed role of catalase in cellular proctetion under SMF.  Exposition to SMF should be further validated in vitro and in vivo as a potential therapeutic approach for neurodegenerative disorders.

Role of P2X7 Receptors in Immune Responses During Neurodegeneration.

P2X7 receptors are ion-gated channels activated by ATP. Under pathological conditions, the extensive release of ATP induces sustained P2X7 receptor activation, culminating in induction of proinflammatory pathways with inflammasome assembly and cytokine release. These inflammatory conditions, whether occurring peripherally or in the central nervous system (CNS), increase blood-brain-barrier (BBB) permeability. Besides its well-known involvement in neurodegeneration and neuroinflammation, the P2X7 receptor may induce BBB disruption and chemotaxis of peripheral immune cells to the CNS, resulting in brain parenchyma infiltration. For instance, despite common effects on cytokine release, P2X7 receptor signaling is also associated with metalloproteinase secretion and activation, as well as migration and differentiation of T lymphocytes, monocytes and dendritic cells. Here we highlight that peripheral immune cells mediate the pathogenesis of Multiple Sclerosis and Parkinson's and Alzheimer's disease, mainly through T lymphocyte, neutrophil and monocyte infiltration. We propose that P2X7 receptor activation contributes to neurodegenerative disease progression beyond its known effects on the CNS. This review discusses how P2X7 receptor activation mediates responses of peripheral immune cells within the inflamed CNS, as occurring in the aforementioned diseases.