FETUS STATE ASSESSMENT AND PECULIARITIES OF NEONATAL PERIOD COURSE IN CHILDREN BORN TO WOMEN OF LATE REPRODUCTIVE AGE IN THE CHECHEN REPUBLIC

Objective of the research: conduct a Doppler ultrasound (DUS) assessment of utero-placentalfetal blood flow and the condition of newborns in the early neonatal period from women of the late reproductive period (LRP), depending on the parity of delivery, using the example of women in the Chechen Republic. Material and methods: retrospective multicenter study. DUS assessment of the state of utero-placental-fetal blood flow and the state of newborns in the early neonatal period was performed in 95 pregnant women, including: group 1–35 primiparous of LRP and their 35 newborns, group 2 – 35 multi-pregnant (MP) of LRP and their 35 newborns. The 3 control group included 25 healthy pregnant women aged 18 to 25 years and their 25 newborns. DUS was performed on Aloka SD SSD 3500 device (Japan), and a transvaginal sensor was used if necessary. Newborns were assessed on the APGAR score at 1 and 5 minutes after birth. Of the instrumental methods for examining newborns, brain ultrasound examination (neurosonography) was used. Results: analyzing the DUS results of LRP pregnant, depending on the labor parity, it was found that in the 1st group there was an increase in resistance in both uterine arteries (61%), an increase in the resistance index and pulsation index, a decrease in diastolic blood flow, characteristic of arteries with high resistance. Hemodynamic parameters in the mid-brain artery (MBA) of the fetus remained normal in all pregnant women. LRP women often born children in a state of asphyxia, with neurological disorders, and these children often has more complex postnatal adaptation and concomitant pathology. Among LRP women, primiparous has significantly more severe disorders. Conclusion: the data of uteroplacental fetal blood flow of the 1st group correspond to blood flow disorders of the IA degree, which indirectly indicates a compensatory reaction of the vascular system of uteroplacental fetal blood flow, as well as the absence of a tendency to an increase in the severity of fetoplacental insufficiency. It is possible that high incidence of neurological disorders in children born to LRP women is associated with age-related changes in their germ cells, use of assisted reproductive technologies, intake of hormonal drugs at an early stage of pregnancy and environmental factors associated with iodine deficiency in the region which includes the North Caucasus.

A pilot study on biaxial mechanical, collagen microstructural, and morphological characterizations of a resected human intracranial aneurysm tissue

Intracranial aneurysms (ICAs) are focal dilatations that imply a weakening of the brain artery. Incidental rupture of an ICA is increasingly responsible for significant mortality and morbidity in the American’s aging population. Previous studies have quantified the pressure-volume characteristics, uniaxial mechanical properties, and morphological features of human aneurysms. In this pilot study, for the first time, we comprehensively quantified the mechanical, collagen fiber microstructural, and morphological properties of one resected human posterior inferior cerebellar artery aneurysm. The tissue from the dome of a right posterior inferior cerebral aneurysm was first mechanically characterized using biaxial tension and stress relaxation tests. Then, the load-dependent collagen fiber architecture of the aneurysm tissue was quantified using an in-house polarized spatial frequency domain imaging system. Finally, optical coherence tomography and histological procedures were used to quantify the tissue’s microstructural morphology. Mechanically, the tissue was shown to exhibit hysteresis, a nonlinear stress-strain response, and material anisotropy. Moreover, the unloaded collagen fiber architecture of the tissue was predominantly aligned with the testing Y-direction and rotated towards the X-direction under increasing equibiaxial loading. Furthermore, our histological analysis showed a considerable damage to the morphological integrity of the tissue, including lack of elastin, intimal thickening, and calcium deposition. This new unified characterization framework can be extended to better understand the mechanics-microstructure interrelationship of aneurysm tissues at different time points of the formation or growth. Such specimen-specific information is anticipated to provide valuable insight that may improve our current understanding of aneurysm growth and rupture potential.

Clinical Case: Complications after Endovascular Treatment of Intracranial Aneurysm in a Patient after Subarachnoid Hemorrhage

Intracranial aneurysm is one of the most common neurovascular complications. During the recent years the accepted treatment of enraptured cranial aneurysm is noninvasive endovascular coiling. This technique is modern but it is not without complications which can be serious and life-threatening. A clinical case of a patient admitted to the ICU of Military Medical Academy - Sofia with sub arachnoid hemorrhage is described. After a positive clinical course, the check-up magnetic resonance showed intracranial aneurism of the right carotid artery. The patient underwent angiographic endovascular treatment. Vasospasm of the middle and right brain artery and thrombosis were detected during the procedure. Attempt of thromboaspiration was made without success. This article reviews published data on broad-spectrum researches concerning complications of endovascular coiling of intracranial aneurysms and the ways to prevent and reduce them.

The Correlation Between Ischemic Stroke and Thrombosis by Nanoscale Biomarker Analysis

Ischemic stroke, which is the fifth leading cause of death, is an attack in the brain due to blockage of a brain artery. It occurs when a sudden loss of blood flow to the brain leads to a reduction in the oxygen supply. A wide range of reasons have been found for ischemic stroke, including high blood pressure and associated thrombosis. Suitable biomarker analysis followed by proper treatment helps to prevent ischemic stroke. An aptamer is an artificial antibody generated against various clinical biomarkers from a smaller molecule of a whole cell. Recently, several researchers conducted biomarker analysis for ischemic stroke using aptamers. Furthermore, factor IX, which is a blood clotting factor, is highly correlated with thrombosis and plays a role in ischemic stroke. In this review, we summarized the potential role of aptamers in ischemic stroke by nanoscale analysis, and factor IX was the distinct focus of this review.

Platelets in Thrombo-Inflammation: Concepts, Mechanisms, and Therapeutic Strategies for Ischemic Stroke

Platelets are anucleate cells known for their essential function in hemostasis and formation of thrombi under pathologic conditions. In recent years, strong evidence emerged demonstrating the critical involvement of platelets in inflammatory processes including acute ischemic stroke (AIS), which is one of the leading causes of death and disability worldwide. Recanalization of the occluded brain artery to reconstitute cerebral blood flow is the primary goal in the treatment of stroke patients. However, despite successful reperfusion many patients show progression of infarct sizes, a phenomenon referred to as ischemia/reperfusion injury (I/RI). Cerebral I/RI involves both thrombotic as well as inflammatory pathways acting in concert to cause tissue damage, defining AIS as a prototypic thrombo-inflammatory disease. Currently used antiplatelet drugs applied to AIS patients eventually increase the risk of partially life-threatening hemorrhages, making more targeted pharmacological intervention necessary. Experimental evidence indicates that inhibition of platelet surface receptors that regulate initial platelet adhesion and activation might be suitable targets in thrombo-inflammatory settings, while inhibitors of platelet aggregation are not. In this review, we will summarize the recent developments in elucidating the role of the main platelet receptors in AIS and discuss their potential as pharmaceutical targets. Furthermore, we will also briefly discuss the important platelet-triggered intrinsic coagulation pathway with the pro-inflammatory kallikrein–kinin system in the context of ischemic stroke.

Mechanical recanalization for acute bilateral cerebral artery occlusion – literature overview with a case

BackgroundAcute bilateral internal carotid artery (ICA) and/or middle cerebral artery (MCA) occlusion is extremely rare and associated with poor clinical outcomes. There are only a few reports in the literature about mechanical thrombectomy being performed for acute bilateral occlusions. The treatment strategies and prognoses (clinical outcomes) are therefore unclear.MethodsA systematic review of the literature was performed through several electronic databases with the following search terms: acute bilateral stroke, mechanical recanalization and thrombectomy.ResultsIn the literature, we identified five reports of six patients with bilateral ICA and/or MCA occlusion treated with mechanical recanalization. Additionally, we report our experience with a subsequent contralateral large brain artery occlusion during intravenous thrombolytic therapy, where the outcome after mechanical thrombectomy was not dependent on the time from stroke onset but rather on the capacity of collateral circulation exclusively.ConclusionsAcute bilateral cerebral (ICA and/or MCA) occlusion leads to sudden severe neurological deficits (comas) with unpredicted prognoses, even when mechanical recanalization is available. As the collateral capacity seems to be more important than the absolute time to flow restoration in determining the outcomes, simultaneous thrombectomy by itself probably does not lead to improved functional outcomes.

Study of the new 4-phenylpyrrolidinone-2 derivative pharmacokinetics and neuroprotective effect in the ischemic stroke animal model

The development of methods of drug therapy and rehabilitation in different periods of ischemic cerebral lesion is currently an urgent problem. Our study was aimed to investigate the pharmacokinetics and anti-ischemic effect of the new 4-phenylpyrrolidone-2 derivative in rats. To study the drug pharmacokinetics, the Wistar rats were once administered with the substance at a dose of 250 mg/kg, then, the substance distribution in blood and cerebral cortex was evaluated. Elimination half-life value was determined, which was 83.2 min. The substance remained in the brain tissue for 24 hours. To assess the anti-ischemic effect, the stroke was modeled by endovascular middle brain artery transition occlusion, and the drug was administered intravenously for 5 days at two doses, 250 and 125 mg/kg. After that the lesion focus volume was evaluated by MRI, as well as the neurological deficit severity, locomotor and explorative behavior. The studied drug significantly decreased the neurological deficit in model animals compared to control group (1.72 vs 4.4, p < 0.05). According to the MRI data, the effect on the ischemic focus was negligible, while the explorative behavior significantly increased under the influence of the 4-phenylpyrrolidone-2 derivative (hole board test, horizontal activity 12.1 ± 6.8, 22.5 ±10.5, p < 0.05). The data obtained allow us to conclude that the studied substance penetrates the blood-brain barrier (BBB), and accumulates in the brain tissue promoting the neurological deficit correction and increasing the explorative behavior in the ischemic stroke model animals.

Case of endovascular treatment of a patient with fusiform aneurysm de novo m2-branch of the middle brain artery

A clinical case with the choice of an individual strategy and tactics of endovascular treatment of a patient with fusiform aneurysm de novo of a branch of the middle cerebral artery is considered. Diagnosis and treatment was carried out in Scientific-practical Center of endovascular neuroradiology of the National Academy of Medical Sciences of Ukraine. Patient B., born in 1996, was admitted to the center in the acute period of hemorrhage from the fusiform aneurysm of the M2-branch of the middle cerebral artery, which, in turn, was excluded from circulation deconstructive, without neurological deficit in the postoperative period. Three months after the first endovascular treatment the patient was re-admitted to the center with the clinical manifestations of spontaneous subarachnoid hemorrhage. According to multispiral computed tomography and selective cerebral angiography, a fusiform aneurysm de novo of M2-branch of the middle cerebral artery was found, which, in turn, was excluded from circulation deconstructive in two stages. The first attempt at endovascular treatment failed to achieve total fusiform aneurysm de novo occlusion using detachable coils, due to the high risk of intraoperative complications. Ten days after the first stage the patient was taken again. Non-standard technique using balloon-assisted adhesive composition made it possible to achieve complete deconstructive occlusion of fusiform aneurysm de novo from the blood stream and to avoid complications in the form of neurological deficit. The postoperative period proceeded without features. In satisfactory condition the patient discharged under the supervision of a neurologist at the place of residence. The patient underwent 4 control examinations in the form of selective cerebral angiography. Collateral blood flow to the branches of the middle cerebral artery is preserved.

Brain-Derived Extracellular Vesicles are Highly Enriched in the Prion Protein and Its C1 Fragment: Relevance for Cellular Uptake and Implications in Stroke

ABSTRACTExtracellular vesicles (EVs) are important means of intercellular communication and a potent tool for regenerative therapy. In ischemic stroke, transient blockage of a brain artery leads to a lack of glucose and oxygen in the affected brain tissue, provoking neuronal death by necrosis in the core of the ischemic region. The fate of neurons in the surrounding penumbra depends on the stimuli, including EVs, received during the following hours. A detailed characterization of such stimuli is crucial not only for understanding stroke pathophysiology but also for new therapeutic interventions.In the present study, we characterize the EVs in mouse brain under physiological conditions and 24h after induction of transient ischemia in mice. We show that, in steady-state conditions, microglia are the main source of small EVs (sEVs) whereas after ischemia, the main EV population originates from astrocytes. Moreover, sEVs presented high amounts of the prion protein (PrP) which were increased after stroke. Conspicuously, sEVs were particularly enriched in a truncated PrP fragment (PrP-C1). Because of similarities between PrP-C1 and certain viral surface proteins, we studied the cellular uptake of brain-derived sEVs from mice lacking (PrP-KO) or containing PrP (WT). We show that PrP-KO-EVs are rapidly taken up by neurons and colocalize with lysosomes. Although eventually WT-EVs are also found in lysosomes, the amount taken up by neurons is significantly higher for PrP-KO-EVs. Likewise, microglia and astrocytes were also engulfing PrP-KO-sEVs more efficiently than WT-sEVs.Our results provide information on the relative contribution of brain cell types to the sEV pool in mice and indicate that increased release of sEVs by astrocytes together with elevated levels of PrP in sEVs may play a role in intercellular communication at early stages after stroke. In addition, amounts of PrP (and probably PrP-C1) in brain sEVs seem to contribute to their cellular uptake.