Cerebral and retinal ischemia share similar pathogenesis and epidemiology, each carrying both acute and prolonged risk of the other and often co-occurring. The most used preclinical stroke models, the Koizumi and Longa middle cerebral artery occlusion (MCAO) methods, have reported retinal damage with great variability, leaving the disruption of retinal blood supply via MCAO poorly investigated, even providing conflicting assumptions on the origin of the ophthalmic artery in rodents. The aim of our study was to use longitudinal in vivo magnetic resonance assessment of cerebral and retinal vascular perfusion after the ischemic injury to clarify whether and how the Koizumi and Longa methods induce retinal ischemia and how they differ in terms of cerebral and retinal lesion evolution. We provided anatomical evidence of the origin of the ophthalmic artery in mice from the pterygopalatine artery. Following the Koizumi surgery, retinal responses to ischemia overlapped with those in the brain, resulting in permanent damage. In contrast, the Longa method produced only extensive cerebral lesions, with greater tissue loss than in the Koizumi method. Additionally, our data suggests the Koizumi method should be redefined as a model of ischemia with chronic hypoperfusion rather than of ischemia and reperfusion.

Neural tube defects (NTDs) are the second most common congenital malformations of humans, characterized by impaired development of the central nervous system. Even though the etiology of most birth defects remains undetermined, genetic and environmental risk factors in the background of NTDs have been identified and extensively reported. On top of genetic and nutritional risks which include mutations in both coding and non-coding regions and maternal folate status, respectively, recent years have seen a rise in the identification of a variety of teratogens that could be implicated in NTD development. These include polycyclic aromatic hydrocarbons, arsenic, pesticides, maternal hyperthermia and antibiotics as well as pain and seizure medication. With an increase in understanding of teratogens leading to NTD formation, preventative and treatment approaches have witnessed great advances throughout the years. While the most common preventative approach includes folic acid food fortification as well as suggested inositol supplementation, treatment and management approaches differ greatly depending on the developmental stage and the site of the lesion and include prenatal surgery, stem cell transplantation and postnatal surgery. Because NTDs still represent a large health and financial burden for the patient and society as a whole, it is crucial to investigate potential risk factors and develop novel approaches in order to fully prevent this category of disorders.

Perinatal brain damage, one of the most common causes of lifelong impairment, is predominantly caused by a lack of oxygen and glucose during early development. These conditions, in turn, affect cells of the nervous tissue through various stages of their maturation. To quantify the influence of these factors on cell differentiation and mitochondrial parameters, we exposed neural cell precursors to oxygen and glucose deprivation (OGD) during three stages of their differentiation: day 1, day 7, and day 14 (D1, D7, and D14, respectively). The obtained results show that OGD slows down cellular differentiation and causes cell death. Regardless of the level of cell maturity, the overall area of the mitochondria, their length, and the branching of their filaments decreased uniformly when exposed to OGD-related stress. Moreover, the cells in all stages of differentiation exhibited an increase in ROS production, hyperpolarization of the mitochondrial membrane, and autophagy. Interestingly, day 7 was the only stage in which a significant increase in mitochondrial fission, along with measurable instances of mitophagy, were detected. Taken together, the results of this study suggest that, apart from common reactions to a sudden lack of oxygen and glucose, cells in specific stages of neural differentiation can also exhibit increased preferences for mitochondrial fission and mitophagy. Such findings could play a role in guiding the future development of novel therapeutic approaches targeting perinatal brain damage during specific stages of nervous system development.

Background: Ondansetron and paracetamol are often co-administrated to prevent and treat nausea and vomiting caused by anaesthesia and to control of postoperative pain. In addition, ondansetron is used as the first-line antiemetic in paracetamol overdose. Therefore, selective and sensitive method for their simultaneous analysis is of a great importance. The electroanalytical methods are highly sensitive and offer many possibilities for new sensor platform design. However, at present, no electroanalytical method for simultaneous determination of these drugs has been proposed. Objective: The aim of this study was to develop a novel nanosensor for selective monitoring of ondansetron and paracetamol in pharmaceutical and biological samples without expensive and time-consuming pretreatments. Methods: The graphitized multi-walled carbon nanotubes embedded in a cation exchange polymer matrix was selected, among various surface functionalizations evaluated, to design novel sensor. Based on its excellent sensing performance, the first electroanalytical method was developed for rapid concurrent determination of investigated drugs. Results: The scanning electron microscopy study showed interlinked nanoporous network structure and highly enlarged active surface. The developed sensor facilitated electron transfer in the oxidation of both drugs and tremendously enhanced the adsorption capacity for ondasetron, thus exhibiting significant increase of drug responses and sensitivity. To obtain much sensitive response of investigated drugs the effect of pH values of supporting electrolyte, dispersed nanomaterial amount, the cation exchange polymer concentration, drop-casting volume of nanocomposite suspension, accumulation potential and deposition time on the peak current was evaluated. The developed electroanalytical method was validated and practical utility of the proposed nanosensor was tested. Conclusion: The developed sensor is promising sensing platform with a fast response time for analysis of ondansetron and paracetamol at very different concentration levels found in their fixed-dose combination and human serum sample after recommended daily doses showing its potential usage in pharmaceutical quality control and clinical research.