Hypoxic‐ischaemic episodes experienced at the perinatal period commonly lead to a development of neurological disabilities and cognitive impairments in neonates or later in childhood. Clinical symptoms often are associated with the observed alterations in white matter in the brains of diseased children, suggesting contribution of triggered oligodendrocyte/myelin pathology to the resulting disorders. To date, the processes initiated by perinatal asphyxia remain unclear, hampering the ability to develop preventions. To address the issue, the effects of temporal hypoxia‐ischaemia on survival, proliferation and the myelinating potential of oligodendrocytes were evaluated ex vivo using cultures of hippocampal organotypic slices and in vivo in rat model of perinatal asphyxia. The potential engagement of gelatinases in oligodendrocyte maturation was assessed as well. The results pointed to a significant decrease in the number of oligodendrocyte progenitor cells (OPCs), which is compensated for to a certain extent by the increased rate of OPC proliferation. Oligodendrocyte maturation seemed however to be significantly altered. An ultrastructural examination of selected brain regions performed several weeks after the insult showed however that the process of developing central nervous system myelination proceeds efficiently resulting in enwrapping the majority of axons in compact myelin. The increased angiogenesis in response to neonatal hypoxic‐ischaemic insult was also noticed. In conclusion, the study shows that hypoxic‐ischaemic episodes experienced during the most active period of nervous system development might be efficiently compensated for by the oligodendroglial cell response triggered by the insult. The main obstacle seems to be the inflammatory process modulating the local microenvironment.

In recent years, rare-earth-doped upconverting nanoparticles (UCNPs) have been widely used in different life sciences due to their unique properties. Nanoparticles have become a multifunctional and promising new approach to neurobiological disorders and have shown extraordinary application potential to overcome the problems related to conventional treatment strategies. This study evaluated the internalization mechanisms, bio-distribution, and neurotoxicity of NaYF₄:20%Yb³⁺,2%Er³⁺ UCNPs in rat organotypic hippocampal slices. TEM results showed that UCNPs were easily internalized by hippocampal cells and co-localized with selected organelles inside neurons and astrocytes. Moreover, the UCNPs were taken into the neurons via clathrin- and caveolae-mediated endocytosis. Propidium iodide staining and TEM analysis did not confirm the adverse effects of UCNPs on hippocampal slice viability and morphology. Therefore, UCNPs may be a potent tool for bio-imaging and testing new therapeutic strategies for brain diseases in the future.

Oligodendrocyte progenitor cells (OPCs) constitute one of the main populations of dividing cells in the central nervous system (CNS). Physiologically, OPCs give rise to mature, myelinating oligodendrocytes and confer trophic support to their neighboring cells within the nervous tissue. OPCs are known to be extremely sensitive to the influence of exogenous clues which might affect their crucial biological processes, like survival, proliferation, differentiation, and the ability to generate a myelin membrane. Alterations in their differentiation influencing their final potential for myelinogenesis are usually the leading cause of CNS dys- and demyelination, contributing to the development of leukodystrophic disorders. The evaluation of the mechanisms that cause oligodendrocytes to malfunction requires detailed studies based on designed in vitro models. Since OPCs readily respond to changes in local homeostasis, it is crucial to establish restricted culture conditions to eliminate the potential stimuli that might influence oligodendrocyte biology. Additionally, the in vitro settings should mimic the physiological conditions to enable the obtained results to be translated to future preclinical studies. Therefore, the aim of our study was to investigate OPC differentiation in physiological normoxia (5% O₂) and a restricted in vitro microenvironment. To evaluate the impact of the combined microenvironmental clues derived from other components of the nervous tissue, which are also influenced by the local oxygen concentration, the process of generating OPCs was additionally analyzed in organotypic hippocampal slices. The obtained results show that OPC differentiation, although significantly slowed down, proceeded correctly through its typical stages in the physiologically relevant conditions created in vitro. The established settings were also conducive to efficient cell proliferation, exerting also a neuroprotective effect by promoting the proliferation of neurons. In conclusion, the performed studies show how oxygen tension influences OPC proliferation, differentiation, and their ability to express myelin components, and should be taken into consideration while planning preclinical studies, e.g., to examine neurotoxic compounds or to test neuroprotective strategies.

Perinatal asphyxia results from the action of different risk factors like complications during pregnancy, preterm delivery, or long and difficult labor. Nowadays, it is still the leading cause of neonatal brain injury known as hypoxic-ischemic encephalopathy (HIE) and resulting neurological disorders. A temporal limitation of oxygen, glucose, and trophic factors supply results in alteration of neural cell differentiation and functioning and/or leads to their death. Among the affected cells are oligodendrocytes, responsible for myelinating the central nervous system (CNS) and formation of white matter. Therefore, one of the major consequences of the experienced HIE is leukodystrophic diseases resulting from oligodendrocyte deficiency or malfunctioning. The therapeutic strategies applied after perinatal asphyxia are aimed at reducing brain damage and promoting the endogenous neuroreparative mechanisms. In this review, we focus on the biology of oligodendrocytes and discuss present clinical treatments in the context of their efficiency in preserving white matter structure and preventing cognitive and behavioral deficits after perinatal asphyxia.

Neonatal hypoxia-ischemia is a leading cause of neonatal death in both developed and developing countries. The consequences of hypoxic-ischemic injury affect the rest of the child’s life, often resulting in intellectual or motor disability that persists into adulthood. To date, therapeutic hypothermia (TH) appears to be the only available intervention aimed at limiting brain injury and is recognized as the “gold standard” in neonatal intensive care. The basic mechanisms of neuroprotection achieved by temporal cooling involve the reduction of free radical activity, suppression of the inflammatory response after reperfusion and increased neuronal cell survival. However, the protective effects of hypothermia need to be enhanced by additional therapies that can enhance neuroprotection and support neuroregenerative processes. The components derived from the umbilical cord are thought to confer the above-mentioned beneficial effects. This review summarizes the clinical trials based on stem cell transplantation or umbilical cord milking and presents their effects when supported by official data. The great promise associated with the application of stem cells to neonates suffering from perinatal asphyxia is discussed in the context of the results of their clinical use. Graphical abstract