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Neonatal stroke is similar to the stroke that occurs in adults and produces a significant morbidity and long-term neurologic and cognitive deficits. There are important differences in the factors, clinical events and outcomes associated with the stroke in infants and adults. However, mechanisms underlying age differences in the stroke development remain largely unknown. Therefore, treatment guidelines for neonatal stroke must extrapolate from the adult data that is often not suitable for children. The new information about differences between neonatal and adult stroke is essential for identification of significant areas for future treatment and effective prevention of neonatal stroke. Here, we studied the development of stress-induced hemorrhagic stroke and possible mechanisms underlying these processes in newborn and adult rats. Using histological methods and magnetic resonance imaging, we found age differences in the type of intracranial hemorrhages. Newborn rats demonstrated small superficial bleedings in the cortex while adult rats had more severe deep bleedings in the cerebellum. Using Doppler optical coherent tomography, we found higher stress-reactivity of the sagittal sinus to deleterious effects of stress in newborn vs. adult rats suggesting that the cerebral veins are more vulnerable to negative stress factors in neonatal vs. adult brain in rats. However, adult but not newborn rats demonstrated the stroke-induced breakdown of blood brain barrier (BBB) permeability. The one of possible mechanisms underlying the higher resistance to stress-related stroke injures of cerebral vessels in newborn rats compared with adult animals is the greater expression of two main tight junction proteins of BBB (occludin and claudin-5) in neonatal vs. mature brain in rats.

Recurrent bladder neck sclerosis is one of the common complications of endoscopic treatment of benign prostate hyperplasia, which often leads to multiple re-operations, including complex open and laparoscopic reconstructive procedures. One of the most promising minimally invasive methods for preventing recurrence of bladder neck sclerosis is balloon dilatation under transrectal ultrasound guidance. To improve the results of using this technique, a urethral catheter with a biopolymer coating, capable of depositing a drug and eluting it under the influence of diagnostic ultrasound, was proposed.

It was shown recently that bacterial strains, which can act specifically against malignant cells, can be used efficiently in cancer therapy. Many appropriate bacterial strains are either pathogenic or invasive and there is a substantial shortage of methods with which to monitor in vivo the distribution of bacteria used in this way. Here, it is proposed to use a Layer-by-Layer (LbL) approach that can encapsulate individual bacterial cells with fluorescently labeled polyelectrolytes (PE)s and magnetite nanoparticles (NP)s. The NP enable remote direction in vivo to the site in question and the labeled shells in the far-red emission spectra allow non-invasive monitoring of the distribution of bacteria in the body. The magnetic entrapment of the modified bacteria causes the local concentration of the bacteria to increase by a factor of at least 5. The PEs create a strong barrier, and it has been shown in vitro experiments that the division time of bacterial cells coated in this way can be regulated, resulting in control of their invasion into tissues. That animals used in the study survived and did not suffer septic shock, which can be attributed to PE capsules that prevent release of endotoxins from bacterial cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rybkin, Pinyaev, Sindeeva, German, Koblar, Pyataev, Čeh, Gorin, Sukhorukov and Lapanje.)

Drug carriers based on polyelectrolyte microcapsules remotely controlled with an external magnetic field are a promising drug delivery system. However, the influence of capsule parameters on microcapsules' behavior in vivo is still ambiguous and requires additional study. Here, we discuss how the processes occurring in the blood flow influence the circulation time of magnetic polyelectrolyte microcapsules in mouse blood after injection into the blood circulatory system and their interaction with different blood components, such as WBCs and RBCs. The investigation of microcapsules ranging in diameter 1-5.5 μm allowed us to reveal the dynamics of their filtration by vital organs, cytotoxicity, and hemotoxicity, which is dependent on their size, alongside the efficiency of their interaction with the magnetic field. Our results show that small capsules have a long circulation time and do not affect blood cells. In contrast, the injection of large 5.5 μm microcapsules leads to fast filtration from the blood flow, induces the inhibition of macrophage cell line proliferation after 48 h, and causes an increase in hemolysis, depending on the carrier concentration. The obtained results reveal the possible directions of fine-tuning microcapsule parameters, maximizing capsule payload without the side effects for the blood flow or the blood cells.

A new application of the photodynamic treatment (PDT) is presented for the opening of blood-brain barrier (BBB) and the brain clearing activation that is associated with it, including the use of gold nanoparticles as emerging photosensitizer carriers in PDT. The obtained results clearly demonstrate 2 pathways for the brain clearing: (1) using PDT-opening of BBB and intravenous injection of FITC-dextran we showed a clearance of this tracer via the meningeal lymphatic system in the subdural space; (2) using optical coherence tomography and intraparenchymal injection of gold nanorods, we observed their clearance through the exit gate of cerebral spinal fluid from the brain into the deep cervical lymph node, where the gold nanorods were accumulated. These data contribute to a better understanding of the cerebrovascular effects of PDT and shed light on mechanisms, underlying brain clearing after PDT-related opening of BBB, including clearance from nanoparticles as drug carriers., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nano- and microencapsulation has proven to be a useful technique for the construction of drug delivery vehicles for use in vascular medicine. However, the possibility of using these techniques within the lung as an inhalation delivery mechanism has not been previously considered. A critical element of particle delivery to the lung is the degree of penetrance that can be achieved with respect to the airway tree. In this study we examined the effectiveness of near infrared (NIR) dye (Cy7) labeled calcium carbonate (vaterite) particles of 3.15, 1.35, and 0.65 μm diameter in reaching the respiratory portion of the lung. First of all, it was shown that, interaction vaterite particles and the components of the pulmonary surfactant occurs a very strong retardation of the recrystallization and dissolution of the particles, which can subsequently be used to create systems with a prolonging release of bioactive substances after the particles penetrate the distal sections of the lungs. Submicro- and microparticles, coated with Cy7 labeled albumin as a model compound, were delivered to mouse lungs via tracheostomy with subsequent imaging performed 24, 48, and 72 h after delivery by in vivo fluorescence. 20 min post administration particles of all three sizes were visible in the lung, with the deepest penetrance observed with 0.65 μm particles. In vivo biodistribution was confirmed by fluorescence tomography imaging of excised organs post 72 h. Laser scanning confocal microscopy shows 0.65 μm particles reaching the alveolar space. The delivery of fluorophore to the blood was assessed using Cy7 labeled 0.65 μm particles. Cy7 labeled 0.65 μm particles efficiently delivered fluorescent material to the blood with a peak 3 h after particle administration. The pharmacokinetics of NIR fluorescence dye will be shown. These studies establish that by using 0.65 μm particles loaded with Cy7 we can efficiently access the respiratory portion of the lung, which represents a potentially efficient delivery mechanism for both the lung and the vasculature.

Photodynamic treatment (PDT) causes a significant increase in the permeability of the blood-brain barrier (BBB) in healthy mice. Using different doses of laser radiation (635 nm, 10-40 J/cm 2 ) and photosensitizer (5-aminolevulinic acid - 5-ALA, 20 and 80 mg/kg, i.v.), we found that the optimal PDT for the reversible opening of the BBB is 15 J/cm 2 and 5-ALA, 20 mg/kg, exhibiting brain tissues recovery 3 days after PDT. Further increases in the laser radiation or 5-ALA doses have no amplifying effect on the BBB permeability, but are associated with severe damage of brain tissues. These results can be an informative platform for further studies of new strategies in brain drug delivery and for better understanding of mechanisms underlying cerebrovascular effects of PDT-related fluorescence guided resection of brain tumor., Competing Interests: The authors declare that there are no conflicts of interest related to this article.

Laser speckle contrast imaging (LSCI) has become one of the most common tools for functional imaging in tissues. Incomplete theoretical description and sophisticated interpretation of measurement results are completely sidelined by a low-cost and simple hardware, fastness, consistent results, and repeatability. In addition to the relatively low measuring volume with around 700 ?? ? m of the probing depth for the visible spectral range of illumination, there is no depth selectivity in conventional LSCI configuration; furthermore, in a case of high NA objective, the actual penetration depth of light in tissues is greater than depth of field (DOF) of an imaging system. Thus, the information about these out-of-focus regions persists in the recorded frames but cannot be retrieved due to intensity-based registration method. We propose a simple modification of LSCI system based on the off-axis holography to introduce after-registration refocusing ability to overcome both depth-selectivity and DOF problems as well as to get the potential possibility of producing a cross-section view of the specimen.

Stress is a major factor for a risk of cerebrovascular catastrophes. Studying of mechanisms underlying stress-related brain-injures in neonates is crucial for development of strategy to prevent of neonatal stroke. Here, using a model of sound-stress-induced intracranial hemorrhages in newborn rats and optical methods, we found that cerebral veins are more sensitive to the deleterious effect of stress than arteries and microvessels. The development of venous insufficiency with decreased blood outflow from the brain accompanied by hypoxia, reduction of complexity of venous blood flow and high production of beta-arrestin-1 are possible mechanisms responsible for a risk of neonatal hemorrhagic stroke.