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Central nervous system (CNS) diseases represent an extreme burden with significant social and economic costs. A common link in most brain pathologies is the appearance of inflammatory components that can jeopardize the stability of the implanted biomaterials and the effectiveness of therapies. Different silk fibroin scaffolds have been used in applications related to CNS disorders. Although some studies have analyzed the degradability of silk fibroin in non-cerebral tissues (almost exclusively upon non-inflammatory conditions), the stability of silk hydrogel scaffolds in the inflammatory nervous system has not been studied in depth. In this study, the stability of silk fibroin hydrogels exposed to different neuroinflammatory contexts has been explored using an in vitro microglial cell culture and two in vivo pathological models of cerebral stroke and Alzheimer's disease. This biomaterial was relatively stable and did not show signs of extensive degradation across time after implantation and during two weeks of in vivo analysis. This finding contrasted with the rapid degradation observed under the same in vivo conditions for other natural materials such as collagen. Our results support the suitability of silk fibroin hydrogels for intracerebral applications and highlight the potentiality of this vehicle for the release of molecules and cells for acute and chronic treatments in cerebral pathologies. [ABSTRACT FROM AUTHOR]

Magnetic hyperthermia (MHT) is an oncological therapy that uses magnetic nanoparticles (MNPs) to generate localized heat under a low-frequency alternating magnetic field (AMF). Recently, trapezoidal pulsed alternating magnetic fields (TPAMFs) have proven their efficacy in enhancing the efficiency of heating in MHT as compared to the sinusoidal one. Our study aims to compare the TPAMF waveform's killing effect against the sinusoidal waveform in B16F10 and CT2A cell lines to determine more efficient waveforms in causing cell death. For that purpose, we used MNPs and different AMF waveforms: trapezoidal (TP), almost-square (TS), triangular (TR), and sinusoidal signal (SN). MNPs at 1 and 4 mg/mL did not affect cell viability during treatment. The exposition of B16F10 and CT2A cells to only AMF showed nonsignificant mortality. Hence, the synergetic effect of the AMF and MNPs causes the observed cell death. Among the explored cases, the nonharmonic signals demonstrated better efficacy than the SN one as an MHT treatment. This study has revealed that the application of TP, TS, or TR waveforms is more efficient and has considerable capability to increase cancer cell death compared to the traditional sinusoidal treatment. Overall, we can conclude that the application of nonharmonic signals enhances MHT treatment efficiency against tumor cells. [ABSTRACT FROM AUTHOR]

After an injury, the limited regenerative capacity of the central nervous system makes the reconnection and functional recovery of the affected nervous tissue almost impossible. To address this problem, biomaterials appear as a promising option for the design of scaffolds that promote and guide this regenerative process. Based on previous seminal works on the ability of regenerated silk fibroin fibers spun through the straining flow spinning (SFS) technique, this study is intended to show that the usage of functionalized SFS fibers allows an enhancement of the guidance ability of the material when compared with the control (nonfunctionalized) fibers. It is shown that the axons of the neurons not only tend to follow the path marked by the fibers, in contrast to the isotropic growth observed on conventional culture plates, but also that this guidance can be further modulated through the biofunctionalization of the material with adhesion peptides. Establishing the guidance ability of these fibers opens the possibility of their use as implants for spinal cord injuries, so that they may represent the core of a therapy that would allow the reconnection of the injured ends of the spinal cord. [ABSTRACT FROM AUTHOR]

High-performance regenerated silkworm (Bombyx mori) silk fibers can be produced efficiently through the straining flow spinning (SFS) technique. In addition to an enhanced biocompatibility that results from the removal of contaminants during the processing of the material, regenerated silk fibers may be functionalized conveniently by using a range of different strategies. In this work, the possibility of implementing various functionalization techniques is explored, including the production of fluorescent fibers that may be tracked when implanted, the combination of the fibers with enzymes to yield fibers with catalytic properties, and the functionalization of the fibers with cell-adhesion motifs to modulate the adherence of different cell lineages to the material. When considered globally, all these techniques are a strong indication not only of the high versatility offered by the functionalization of regenerated fibers in terms of the different chemistries that can be employed, but also on the wide range of applications that can be covered with these functionalized fibers. [ABSTRACT FROM AUTHOR]

Brain stroke is a highly prevalent pathology and a main cause of disability among older adults. If not promptly treated with recanalization therapies, primary and secondary mechanisms of injury contribute to an increase in the lesion, enhancing neurological deficits. Targeting excitotoxicity and oxidative stress are very promising approaches, but only a few compounds have reached the clinic with relatively good positive outcomes. The exploration of novel targets might overcome the lack of clinical translation of previous efficient preclinical neuroprotective treatments. In this study, we examined the neuroprotective properties of 2-aminoethoxydiphenyl borate (2-APB), a molecule that interferes with intracellular calcium dynamics by the antagonization of several channels and receptors. In a permanent model of cerebral ischemia, we showed that 2-APB reduces the extent of the damage and preserves the functionality of the cortical territory, as evaluated by somatosensory evoked potentials (SSEPs). While in this permanent ischemia model, the neuroprotective effect exerted by the antioxidant scavenger cholesteronitrone F2 was associated with a reduction in reactive oxygen species (ROS) and better neuronal survival in the penumbra, 2-APB did not modify the inflammatory response or decrease the content of ROS and was mostly associated with a shortening of peri-infarct depolarizations, which translated into better cerebral blood perfusion in the penumbra. Our study highlights the potential of 2-APB to target spreading depolarization events and their associated inverse hemodynamic changes, which mainly contribute to extension of the area of lesion in cerebrovascular pathologies. [ABSTRACT FROM AUTHOR]

During the transition from neonate to adulthood, brain maturation establishes coherence between behavioral states—wakefulness, non-rapid eye movement, and rapid eye movement sleep. In animal models few studies have characterized and analyzed cerebral rhythms and the sleep–wake cycle in early ages, in relation to adulthood. Since the analysis of sleep in early ages can be used as a predictive model of brain development and the subsequent emergence of neural disturbances in adults, we performed a study on late neonatal mice, an age not previously characterized. We acquired longitudinal 24 h electroencephalogram and electromyogram recordings and performed time and spectral analyses. We compared both age groups and found that late neonates: (i) spent more time in wakefulness and less time in non-rapid eye movement sleep, (ii) showed an increased relative band power in delta, which, however, reduced in theta during each behavioral state, (iii) showed a reduced relative band power in beta during wakefulness and non-rapid eye movement sleep, and (iv) manifested an increased total power over all frequencies. The data presented here might have implications expanding our knowledge of cerebral rhythms in early ages for identification of potential biomarkers in preclinical models of neurodegeneration. [ABSTRACT FROM AUTHOR]

For decades now, conventional sinusoidal signals have been exclusively used in magnetic hyperthermia as the only alternating magnetic field waveform to excite magnetic nanoparticles. However, there are no theoretical nor experimental reasons that prevent the use of different waveforms. The only justifiable motive behind using the sinusoidal signal is its availability and the facility to produce it. Following the development of a configurable alternating magnetic field generator, we aim to study the effect of various waveforms on the heat production effectiveness of magnetic nanoparticles, seeking to prove that signals with more significant slope values, such as the trapezoidal and almost-square signals, allow the nanoparticles to reach higher efficiency in heat generation. Furthermore, we seek to point out that the nanoparticle power dissipation is dependent on the waveform's slope and not only the frequency, magnetic field intensity and the nanoparticle size. The experimental results showed a remarkably higher heat production performance of the nanoparticles when exposed to trapezoidal and almost-square signals than conventional sinusoidal signals. We conclude that the nanoparticles respond better to the trapezoidal and almost-square signals. On the other hand, the experimental results were used to calculate the normalized power dissipation value and prove its dependency on the slope. However, adjustments are necessary to the coil before proceeding with in vitro and in vivo studies to handle the magnetic fields required. [ABSTRACT FROM AUTHOR]