Brain Blood Research Articles

EARLY STROKE PREVENTION BY IMPROVING THE ROLE OF TEACHERS AND STUDENTS

Background. Stroke is a disease of acute decreased nerve function caused by sudden disruption of the brain's blood vessels. Some efforts to prevent strokes need to be carried out at an early age by controlling risk factors for stroke, particularly stroke risk factors in high school adolescents. According to a local survey, almost 90% of teenagers or students of SMK 1 in the 2nd grade have smoking habits, and the number of teenagers who like fast food that is high in carbohydrates, high in fat, high in cholesterol, and do not do any physical exercises regularly. This empowerment aimed to increase the knowledge and skills of teachers and students regarding early stroke prevention. Implementation Method. The Community Service was conducted in 2023. These empowerment methods used public education, counseling, workshops, and practicum. Partners in this empowerment were the teachers and students of SMKN 1 Suruh, Trenggalek, East Java, with 40 students and 6 teachers. Findings. This study showed the increased knowledge of teachers and students about stroke risk factors and early stroke prevention, as well as increased skills in measuring blood pressure. There were 50% of students had sufficient knowledge about stroke risk factors, 50% had adequate skills in measuring BP, and 92.5% of students had a smoking history. Conclusion. In conclusion, knowledge about stroke risk factors and early prevention of stroke must be carried out starting from an early age, because stroke strikes anyone and varied ages.

Telomere length as a biomarker for cerebrovascular diseases: current evidence.

Cerebrovascular disease (CVD) includes a range of conditions affecting the brain's blood vessels, which can result in reduced blood flow to brain tissue. The most common manifestation of CVD is stroke, the second leading cause of death and the third leading cause of disability worldwide. Major risk factors for CVD encompass gender, age, smoking, hypertension, diabetes, physical inactivity, obesity, alcohol consumption, and metabolic syndrome. Research suggests a link between telomere length and an increased risk of CVD, particularly in ischemic stroke cases. This review highlights key findings on the relationship between telomere length and CVD, underscoring its clinical importance. The analysis utilizes scientific literature from PubMed, Scopus, and SciELO up to 2024. Results show that shorter telomere length is associated with various types of CVD, including stroke, ischemic stroke, hemorrhagic stroke, and cardioembolic stroke. Some studies propose that telomere length measurement could be a valuable biomarker for CVD, potentially improving prevention, diagnosis, and management strategies.

DDEL-11. PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELING OF SPATIAL HETEROGENEITY OF DRUG PENETRATION AND EXPOSURE IN THE HUMAN BRAIN AND BRAIN TUMORS

Abstract BACKGROUD The difficulty in early, reliable prediction of drug penetration and exposure in the human brain and brain tumors makes development of new drugs and use of existing drugs for treating brain cancer a challenging and often unsuccessful task. We developed a physiologically based pharmacokinetic (PBPK) model platform for prediction of spatial pharmacokinetics in the central nervous system (CNS) following systemic drug administration. METHODS A 9-compartment CNS (9-CNS) PBPK model was developed to predict drug concentrations in brain blood, 2 brain parenchyma compartments (brain tissue adjacent to the CSF tract and deep brain parenchyma), 3 CSF compartments (ventricular CSF, cranial and spinal subarachnoid CSF), and 3 tumor compartments (tumor rim, bulk tumor, and tumor core). The pharmacokinetics in the CNS compartments were driven by plasma concentrations and governed by drug properties and CNS pathophysiology. The 9-CNS model was developed and validated with 4 drugs (abemaciclib, ribociclib, ceritinib, and temuterkib). RESULTS When considering tumor heterogeneity and inter-individual plasma pharmacokinetic variability following clinical standard dosing regimens, the model-predicted steady-state unbound drug tumor concentrations varied from 7.1 to 356 nM for abemaciclib, 74 to 4577 nM for ribociclib, 0.66 to 97 nM for ceritinib, and 0.8 to 288 nM for temuterkib, which were consistent with the heterogeneous drug tumor concentrations observed in glioblastoma patients. Drug penetration into the deep brain parenchyma was significantly less than that into tumors and CSF-adjacent brain tissue, particularly for strong ABCB1/ABCG2 substrate drugs. The ventricular and cranial subarachnoid CSF shared similar pharmacokinetics, while the spinal CSF pharmacokinetics was different. CONCLUSION A novel 9-CNS PBPK model was developed and validated for mechanistic prediction of spatial heterogeneity of drug penetration and exposure in the human brain, brain tumors, and CSF. It provides a valuable computational modeling tool to assist development and design of improved drugs or dosing regimens for brain cancer treatment.

Role of Nanotechnology in Combating Ischemic Stroke

Introduction Stroke is a prevalent neurological disorder caused either by an interruption in the brain's blood supply or a loss of vascular integrity, leading to bleeding within brain tissue, and resulting in neuronal damage.

Hybrid Ensemble Deep Learning Model for Advancing Ischemic Brain Stroke Detection and Classification in Clinical Application.

Ischemic brain strokes are severe medical conditions that occur due to blockages in the brain's blood flow, often caused by blood clots or artery blockages. Early detection is crucial for effective treatment. This study aims to improve the detection and classification of ischemic brain strokes in clinical settings by introducing a new approach that integrates the stroke precision enhancement, ensemble deep learning, and intelligent lesion detection and segmentation models. The proposed hybrid model was trained and tested using a dataset of 10,000 computed tomography scans. A 25-fold cross-validation technique was employed, while the model's performance was evaluated using accuracy, precision, recall, and F1 score. The findings indicate significant improvements in accuracy for different stages of stroke images when enhanced using the SPEM model with contrast-limited adaptive histogram equalization set to 4. Specifically, accuracy showed significant improvement (from 0.876 to 0.933) for hyper-acute stroke images; from 0.881 to 0.948 for acute stroke images, from 0.927 to 0.974 for sub-acute stroke images, and from 0.928 to 0.982 for chronic stroke images. Thus, the study shows significant promise for the detection and classification of ischemic brain strokes. Further research is needed to validate its performance on larger datasets and enhance its integration into clinical settings.

Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood.

The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) included the central nucleus of the amygdala, hippocampal dentate gyrus, and medial prefrontal cortex (mPFC). Genes and exons within the mPFC carried most disease signals replicated across two independent cohorts. Pathways pointed to immune function, neuronal and synaptic regulation, and stress hormones. Multiomic factor and gene network analyses provided the underlying genomic structure. Single nucleus RNA sequencing in dorsolateral PFC revealed dysregulated (stress-related) signals in neuronal and non-neuronal cell types. Analyses of brain-blood intersections in >50,000 UK Biobank participants were conducted along with fine-mapping of the results of PTSD and MDD genome-wide association studies to distinguish risk from disease processes. Our data suggest shared and distinct molecular pathology in both disorders and propose potential therapeutic targets and biomarkers.

VesselBoost: A Python Toolbox for Small Blood Vessel Segmentation in Human Magnetic Resonance Angiography Data.

Magnetic resonance angiography (MRA) performed at ultra-high magnetic field provides a unique opportunity to study the arteries of the living human brain at the mesoscopic level. From this, we can gain new insights into the brain's blood supply and vascular disease affecting small vessels. However, for quantitative characterization and precise representation of human angioarchitecture to, for example, inform blood-flow simulations, detailed segmentations of the smallest vessels are required. Given the success of deep learning-based methods in many segmentation tasks, we here explore their application to high-resolution MRA data, and address the difficulty of obtaining large data sets of correctly and comprehensively labelled data. We introduce VesselBoost, a vessel segmentation package, which utilizes deep learning and imperfect training labels for accurate vasculature segmentation. Combined with an innovative data augmentation technique, which leverages the resemblance of vascular structures, VesselBoost enables detailed vascular segmentations.

EEG biomarkers analysis in different cognitive impairment after stroke: an exploration study.

Stroke is a cerebrovascular illness that brings about the demise of brain tissue. It is the third most prevalent cause of mortality worldwide and a significant contributor to physical impairment. Generally, stroke is triggered by blood clots obstructing the brain's blood vessels, or when these vessels rupture. And, the cognitive impairment's evaluation and detection after stroke is crucial research issue and significant project. Thus, the objective of this work is to explore an potential neuroimage tool and find their EEG biomarkers to evaluate and detect four cognitive impairment levels after stroke. In this study, power density spectrum (PSD), functional connectivity map, and one-way ANOVA methods were proposed to analyze the EEG biomarker differences, and the number of patient participants were thirty-two human including eight healthy control, mild, moderate, severe cognitive impairment levels, respectively. Finally, healthy control has significant PSD differences compared to mid, moderate and server cognitive impairment groups. And, the theta and alpha bands of severe cognitive impairment groups have presented consistent superior PSD power at the right frontal cortex, and the theta and beta bands of mild, moderated cognitive impairment (MoCI) groups have shown significant similar superior PSD power tendency at the parietal cortex. The significant gamma PSD power difference has presented at the left-frontal cortex in the mild cognitive impairment (MCI) groups, and severe cognitive impairment (SeCI) group has shown the significant PSD power at the gamma band of parietal cortex. At the point of functional connectivity map, the SeCI group appears to have stronger functional connectivity compared to the other groups. In conclusion, EEG biomarkers can be applied to classify different cognitive impairment groups after stroke. These findings provide a new approach for early detection and diagnosis of cognitive impairment after stroke and also for the development of new treatment options.

PEMBERDAYAAN MASYARAKAT DALAM UPAYA PENCEGAHAN STROKE DI KELURAHAN TARATARA SATU

About a third of stroke sufferers in the world experience permanent disability. Stroke occurs when the brain's blood vessels fail to supply oxygen to the brain cells or when the brain cells do not receive nutrients and oxygen from the blood. Stroke symptoms usually appear suddenly, with loss of strength on one side of the body, confusion, difficulty speaking and understanding, problems with vision, difficulty walking, headaches, and loss of balance. This can be prevented from happening by adopting a healthy lifestyle. The service method used is the lecture and question and answer method with people who are at risk of stroke. The result of this service activity is that there has been an increase in public knowledge about stroke prevention, which is the result of this service activity. This activity is also very important to carry out, especially targeting people with hypertension who are no longer able to comply with taking anti-hypertension medication and adopting a healthy lifestyle, so they need to provide education or socialization about stroke prevention.

Evaluation of Ouabain's Tissue Distribution in C57/Black Mice Following Intraperitoneal Injection, Using Chromatography and Mass Spectrometry.

Cardiotonic steroids (CTSs), such as digoxin, are used for heart failure treatment. However, digoxin permeates the brain-blood barrier (BBB), affecting central nervous system (CNS) functions. Finding a CTS that does not pass through the BBB would increase CTSs' applicability in the clinic and decrease the risk of side effects on the CNS. This study aimed to investigate the tissue distribution of the CTS ouabain following intraperitoneal injection and whether ouabain passes through the BBB. After intraperitoneal injection (1.25 mg/kg), ouabain concentrations were measured at 5 min, 15 min, 30 min, 1 h, 3 h, 6 h, and 24 h using HPLC-MS in brain, heart, liver, and kidney tissues and blood plasma in C57/black mice. Ouabain was undetectable in the brain tissue. Plasma: Cmax = 882.88 ± 21.82 ng/g; Tmax = 0.08 ± 0.01 h; T1/2 = 0.15 ± 0.02 h; MRT = 0.26 ± 0.01. Cardiac tissue: Cmax = 145.24 ± 44.03 ng/g (undetectable at 60 min); Tmax = 0.08 ± 0.02 h; T1/2 = 0.23 ± 0.09 h; MRT = 0.38 ± 0.14 h. Kidney tissue: Cmax = 1072.3 ± 260.8 ng/g; Tmax = 0.35 ± 0.19 h; T1/2 = 1.32 ± 0.76 h; MRT = 1.41 ± 0.71 h. Liver tissue: Cmax = 2558.0 ± 382.4 ng/g; Tmax = 0.35 ± 0.13 h; T1/2 = 1.24 ± 0.7 h; MRT = 0.98 ± 0.33 h. Unlike digoxin, ouabain does not cross the BBB and is eliminated quicker from all the analyzed tissues, giving it a potential advantage over digoxin in systemic administration. However, the inability of ouabain to pass though the BBB necessitates intracerebral administration when used to investigate its effects on the CNS.

The glymphatic system and cerebral small vessel disease

ObjectivesCerebral small vessel disease is a group of pathologies in which alterations of the brain's blood vessels contribute to stroke and neurocognitive changes. Recently, a neurotoxic waste clearance system composed of perivascular spaces abutting the brain's blood vessels, termed the glymphatic system, has been identified as a key player in brain homeostasis. Given that small vessel disease and the glymphatic system share anatomical structures, this review aims to reexamine small vessel disease in the context of the glymphatic system and highlight novel aspects of small vessel disease physiology. Materials and methodsThis review was conducted with an emphasis on studies that examined aspects of small vessel disease and on works characterizing the glymphatic system. We searched PubMed for relevant articles using the following keywords: glymphatics, cerebral small vessel disease, arterial pulsatility, hypertension, blood-brain barrier, endothelial dysfunction, stroke, diabetes. ResultsCerebral small vessel disease and glymphatic dysfunction are anatomically connected and significant risk factors are shared between the two. These include hypertension, type 2 diabetes, advanced age, poor sleep, obesity, and neuroinflammation. There is clear evidence that CSVD hinders the effective functioning of glymphatic system. ConclusionThese shared risk factors, as well as the model of cerebral amyloid angiopathy pathogenesis, hint at the possibility that glymphatic dysfunction could independently contribute to the pathogenesis of cerebral small vessel disease. However, the current evidence supports a model of cascading dysfunction, wherein concurrent small vessel and glymphatic injury hinder glymphatic-mediated recovery and promote the progression of subclinical to clinical disease.

Dynamic local mRNA localization and translation occurs during the postnatal molecular maturation of perivascular astrocytic processes.

Astrocytes are highly ramified and send out perivascular processes (PvAPs) that entirely sheathe the brain's blood vessels. PvAPs are equipped with an enriched molecular repertoire that sustains astrocytic regulatory functions at the vascular interface. In the mouse, PvAP development starts after birth and is essentially complete by postnatal day (P) 15. Progressive molecular maturation also occurs over this period, with the acquisition of proteins enriched in PvAPs. The mechanisms controlling the development and molecular maturation of PvAPs have not been extensively characterized. We reported previously that mRNAs are distributed unequally in mature PvAPs and are locally translated. Since dynamic mRNA localization and local translation influence the cell's polarity, we hypothesized that they might sustain the postnatal maturation of PvAPs. Here, we used a combination of molecular biology and imaging approaches to demonstrate that the development of PvAPs is accompanied by the transport of mRNA and polysomal mRNA into PvAPs, the development of a rough endoplasmic reticulum (RER) network and Golgi cisternae, and local translation. By focusing on genes and proteins that are selectively or specifically expressed in astrocytes, we characterized the developmental profile of mRNAs, polysomal mRNAs and proteins in PvAPs from P5 to P60. We found that some polysomal mRNAs polarized progressively towards the PvAPs. Lastly, we found that expression and localization of mRNAs in developing PvAPs is perturbed in a mouse model of megalencephalic leukoencephalopathy with subcortical cysts. Our results indicate that dynamic mRNA localization and local translation influence the postnatal maturation of PvAPs.

DDEL-03. PHYSIOLOGICALLY BASED PHARMACOKINETIC (PBPK) MODELING OF HETEROGENEOUS DRUG PENETRATION INTO THE HUMAN BRAIN AND GLIOBLASTOMA

Abstract BACKGROUD Insufficient penetration of potentially effective therapeutic agents across the human blood-brain barrier (BBB) is a hurdle to the effective treatment of brain cancer. The BBB in glioblastoma is disrupted to varying extents. This study was to develop a PBPK model platform for prediction of heterogenous drug penetration into the human brain and glioblastoma. METHODS A 7-compartment CNS (7-CNS) PBPK model platform was developed to predict drug concentrations in the brain blood, brain parenchyma, cranial CSF, spinal CSF, and 3 tumor compartments representing infiltrating tumor (T1) with a slightly disrupted BBB, bulk tumor (T2) with a leaky BBB, and necrotic core (T3) with no blood vessels. The model accounted for brain/tumor general anatomy and regional pathophysiological differences. Drug transfer and fluid balance between compartments were described by differential equations. Simulations were performed using R programming. The model was verified by comparisons of predicted and observed tumor PK data of ribociclib and abemaciclib in glioblastoma patients. RESULTS For ribociclib, the model-predicted mean unbound drug brain-to-plasma ratio (Kp,uu) was 0.17, 2.2, 8.2, 24.9 in normal brain, T1, T2, and T3, respectively; the predicted Kp,uu in T1 and T2 was consistent with observed Kp,uu in non-enhancing (median, 2.0) and enhancing tumors (median, 10.1) from 12 patients. For abemaciclib, the predicted mean Kp,uu was 0.88, 1.4, 6.2, and 3.1 in normal brain, T1, T2, and T3, respectively; the predicted Kp,uu in T1 and T2 agreed with observed Kp,uu in non-enhancing (median, 2.1) and enhancing tumors (median, 7.2) from 38 patients. CONCLUSION The developed PBPK model platform well predicts heterogeneous drug penetration and distribution in normal human brain and different regions of glioblastoma, as verified by ribociclib and abemaciclib. It provides a mechanism-based computational modeling tool to assist the development and design of improved drugs and dosing regimens for more effective treatment of glioblastoma.

Intra-brain vascular models within the ICRP mesh-type adult reference phantoms for applications to internal dosimetry

Objective. Phantoms of the International Commission on Radiological Protection provide a framework for standardized dosimetry. The modeling of internal blood vessels—essential to tracking circulating blood cells exposed during external beam radiotherapy and to account for radiopharmaceutical decays while still in blood circulation—is, however, limited to the major inter-organ arteries and veins. Intra-organ blood is accounted for only through the assignment of a homogeneous mixture of parenchyma and blood [single-region (SR) organs]. Our goal was to develop explicit dual-region (DR) models of intra-organ blood vasculature of the adult male brain (AMB) and adult female brain (AFB). Approach. A total of 4000 vessels were created amongst 26 vascular trees. The AMB and AFB models were then tetrahedralized for coupling to the PHITS radiation transport code. Absorbed fractions were computed for monoenergetic alpha particles, electrons, positrons, and photons for both decay sites within the blood vessels and for tissues outside these vessels. Radionuclide S-values were computed for 22 and 10 radionuclides commonly employed in radiopharmaceutical therapy and nuclear medicine diagnostic imaging, respectively. Main results. For radionuclide decays, values of S(brain tissue ← brain blood) assessed in the traditional manner (SR) were higher than those computed using our DR models by factors of 1.92, 1.49, and 1.57 for therapeutic alpha-emitters, beta-emitters, and Auger electron-emitters, respectively in the AFB and by factors of 1.65, 1.37, and 1.42 for these same radionuclide categories in the AMB. Corresponding ratios of SR and DR values of S(brain tissue ← brain blood) were 1.34 (AFB) and 1.26 (AMB) for four SPECT radionuclides, and were 1.32 (AFB) and 1.24 (AMB) for six common PET radionuclides. Significance. The methodology employed in this study can be explored in other organs of the body for proper accounting of blood self-dose for that fraction of the radiopharmaceutical still in general circulation.

Overview of Risk Factors for Stroke in Stroke Patients in Work Area at Technical Implementation Unit of the Linggang Bigung Public Health Centre

Introduction: Stroke is one of the main health problems, not only in Indonesia but in the world. Stroke occurs when the brain's blood vessels experience a blockage or rupture which results in part of the brain not getting the blood supply that carries the necessary oxygen so that cell/ tissue death occurs. Objective: The purpose of this study was to determine the risk factors for Stroke in Stroke patients in the Linggang Bigung Health Center working area. Methods: This study used a descriptive retrospective research design, with a sample size of 22 respondents. Results and Discussion: The results of the study obtained as many as 7 respondents (32%) each with the latest education not in school and elementary school. The majority of 14 respondents (65%) were >55 years old, with the majority of 13 respondents (59%) being male, 16 respondents (73%) had no family history of Stroke, in this study all respondents had hypertension, 13 respondents (59%) had DM, 18 respondents (82%) each smoked and consumed alcohol, while 21 respondents (95%) were not obese. Conclusion: In this study most, respondents were aged >55 years, male gender, had smoking behavior and alcohol consumption and all respondents in this study had hypertension.

Comparison between clevidipine and nicardipine in cerebrovascular diseases: A systematic review and meta-analysis.

The term "cerebrovascular diseases (CVDs)" refers to a broad category of diseases that affect the brain's blood vessels and cerebral circulation. Controlling acute hypertension (HTN) by antihypertensive drugs such as clevidipine and nicardipine can be a highly efficient method of lowering the incidence of CVDs. This is a systematic review and meta-analysis study. The PubMed, Scopus, and Web of Science online databases and a gray literature search were performed to identify potentially eligible studies. The included studies were observational studies that compared adult patients receiving clevidipine or nicardipine for controlling HTN in the setting of CVD. We reviewed 5 final included articles, including 546 patients. The pooled standardized mean difference (SMD) for time to goal SBP was -0.04 (95 % CI: [-0.66; 0.58], p-value: 0.86, I2: 79.0 %, pooled MD: -12.90min), meaning that the clevidipine group had a shorter time to goal systolic blood pressure (SBP) than the nicardipine group. The pooled SMD for total volume infusion was -0.52 (95 % CI: [-0.93; -0.12], p-value: 0.03, I2: 0.0 %, pooled MD: -1118.81mL), showing a notably lower total volume infused into patients in the clevidipine group. We found that clevidipine reaches the SBP goal faster than nicardipine; however, there was no statistically significant difference between the two drugs. The total volume infused to achieve the goal SBP was significantly lower in the clevidipine group. Further prospective studies are needed to compare clevidipine and nicardipine in CVD patients on a large scale.

Physiologically Based Pharmacokinetic Model of Brain Delivery of Plasma Protein Bound Drugs

IntroductionA physiologically based pharmacokinetic (PBPK) model is developed that focuses on the kinetic parameters of drug association and dissociation with albumin, alpha-1 acid glycoprotein (AGP), and brain tissue proteins, as well as drug permeability at the blood–brain barrier, drug metabolism, and brain blood flow.GoalThe model evaluates the extent to which plasma protein-mediated uptake (PMU) of drugs by brain influences the concentration of free drug both within the brain capillary compartment in vivo and the brain compartment. The model also studies the effect of drug binding to brain tissue proteins on the concentration of free drug in brain.MethodsThe steady state and non-steady state PBPK models are comprised of 11–12 variables, and 18–23 parameters, respectively. Two model drugs are analyzed: propranolol, which undergoes modest PMU from the AGP-bound pool, and imipramine, which undergoes a high degree of PMU from both the albumin-bound and AGP-bound pools in plasma.ResultsThe free propranolol concentration in brain is under-estimated 2- to fourfold by in vitro measurements of free plasma propranolol, and the free imipramine concentration in brain is under-estimated by 18- to 31-fold by in vitro measurements of free imipramine in plasma. The free drug concentration in brain in vivo is independent of drug binding to brain tissue proteins.ConclusionsIn vitro measurement of free drug concentration in plasma under-estimates the free drug in brain in vivo if PMU in vivo from either the albumin and/or the AGP pools in plasma takes place at the BBB surface.

Distribution of Neuroglobin in Pericytes is Associated with Blood-Brain Barrier Leakage against Cerebral Ischemia in Mice.

With emerging data on the various functions of neuroglobin (Ngb), such as neuroprotection and neurogenesis, we investigated the role of Ngb in the neurovascular unit (NVU) of the brain. To study the distribution and function of Ngb after cerebral ischemia, transient middle cerebral artery occlusion (tMCAO) was performed in mice. Brain immunostaining and fluorescence-activated cell sorting were used to analyze the role of Ngb according to the location and cell type. In normal brain tissue, it was observed that Ngb was distributed not only in neurons but also around the brain's blood vessels. Interestingly, Ngb was largely expressed in platelet-derived growth factor receptor β (PDGFRβ)-positive pericytes in the NVU. After tMCAO, Ngb levels were significantly decreased in the core of the infarct, and Ngb and PDGFRβ-positive pericytes were detached from the vasculature. In contrast, in the penumbra of the infarct, PDGFRβ-positive pericytes expressing Ngb were increased compared with that in the core of the infarct. Moreover, the cerebral blood vessels, which have Ngb-positive PDGFRβ pericytes, showed reduced blood-brain barrier (BBB) leakage after tMCAO. It showed that Ngb-positive PDGFRβ pericytes stayed around the endothelial cells and reduced the BBB leakage in the NVU. Our results indicate that Ngb may play a role in attenuating BBB leakage in part by its association with PDGFRβ. In this study, the distribution and function of Ngb in the pericytes of the cerebrovascular system have been elucidated, which contributes to the treatment of stroke through a new function of Ngb.

A neural basis of rational inattention models: consistency of cognitive cost with the mutual information criterion.

The rational inattention model has recently attracted much attention as a promising candidate to model bounded rationality in the research field of decision-making and game theory. However, in contrast to this energetic promotion of the theoretical works, empirical verification of the validity of the RI model has not progressed much. Furthermore, to our knowledge, the central assumption of the RI model, that the amount of mutual information obtained from signals adequately represents the cognitive cost of information, has not been tested from a neuroscientific perspective. The purpose of the present study was to test whether the amount of mutual information adequately represents the cognitive cost of information from a neuroscientific perspective. We proposed a sequential investment task, in which the two main models of RI can be treated simultaneously in a more realistic experimental environment. We used a model-fitting approach to analyze the subjective information cost, and compared the model parameters representing the information cost with the concentration of oxidized hemoglobin in the brain blood. Our results showed that the cost parameter λ of the stochastic choice type model, which fits the behavioral data of the present experiment better than the Kalman filter type model, was significantly positively correlated with the activation status of the rostral prefrontal cortex and dorsolateral prefrontal cortex. The cognitive cost represented by the amount of mutual information employed in the RI model is consistent with the activation of brain regions associated with cognitive cost, and, thus, indirectly supports the assumption of the RI model.

CLINICAL AND LABORATORY PREDICTORS OF SEVERE COVID-19 IN MEN AND WOMEN OF DIFFERENT AGE GROUPS

The large amount of papers on studying severe COVID-19 predictors have been published so far, but unfortunately the identified criteria are not universal for different regions of Russia and for the whole world. Therefore, a decision was made to apply routine research methods and compare the criteria previously proposed by other researchers with the criteria identified by us in patients living in Astrakhan Region. The study aimed at searching for and analyzing clinical and laboratory predictors to improve prediction of severe COVID-19 in men and women of different age groups. Materials and methods. Medical records of 361 patients were used as clinical material to conduct a retrospective study. Four groups with sex and age differencies were formed to verify the factors aggravating the course of COVID-19. Examination was performed according to Version 9 of the Temporary Guidelines for Prevention, Diagnosis and Treatment of the Novel Coronavirus Infection (COVID-19). Results. Clinical evidence on admission included unspecific complaints typical of other acute respiratory diseases – generalized weakness, temperature rise over 37.5° C, dyspnea, dry cough, and compressing pain. The spectrum of comorbid diseases includes hypertension, congestive heart failure, coronary heart disease, diabetes mellitus, and obesity. Conclusions. Delayed hospitalization of patients from the day of disease onset due to nonspecific COVID-19 symptoms is one of the unfavorable clinical predictors. Comorbidities that aggravate the course of COVID-19 are consistent with the comorbid conditions identified by other researchers [1,2]. High levels of procalcitonin, D-dimer, brain natriuretic peptide, lactate dehydrogenase and blood creatinine were identified as the most significant predictors of severe COVID-19 on admission, which is also consistent with the findings of other authors. Laboratory parameters like alanine transaminase > 45 u/l and aspartate transaminase > 55 u/l can be used for male patients aged 55 and older, while an increased leukocyte count > 7.4 ×109/l and C-reactive protein > 82 g/l – for female patients aged 55 and older.