Brain Substance Research Articles

Edema and swelling of the brain: a non-systematic review

Annotation. Edema and swelling of the brain are two stages of the development of complex interrelated processes in the brain substance. This pathological process occurs due to various etiological factors: brain injury, stroke, brain tumors and abscesses, meningitis and encephalitis, hypoxia, general toxicosis, infectious processes, body burns, occlusive hydrocephalus, malignant hypertension, osmotic imbalance. That is why the purpose of this review was the systematization of current and modern scientific sources of literature related to the topic of cerebral edema. The analysis of scientific articles and materials in the scientometric databases UpToDate, MEDLINE (PubMed), ScienceDirect, Web of Science, Google Scholar devoted to the coverage of this problem was performed. The article deals with the issues of etiology, classification, pathogenesis of edema-swelling of the brain. The types of edema-swelling are considered in detail, including a description of its rare subtypes. Macro- and microscopic changes, which are typical for edema and swelling of the brain, are described separately. The peculiarities of therapeutic tactics in the treatment of edema-swelling, considering its pathomorphological aspects, are specified.

Integrated Care for Traumatic Brain Injury, Mental Health, and Substance Use: A Systematic Review

<h3>Objective(s)</h3> To summarize the current levels and types of integrated care for traumatic brain injury (TBI) and mental health and substance use (MHSU) and identify the reported barriers and facilitators to integrated care for TBI and MHSU. <h3>Data Sources</h3> Electronic databases were independently reviewed by two reviewers based on pre-determined eligibility criteria. The search was first conducted in September 2018 and updated in September 2020, with no changes to the search strategy. Where possible, searches were limited to English language and excluded animal studies, conference abstracts, magazines, books, and encyclopedias. <h3>Study Selection</h3> Peer-reviewed primary research articles and dissertations published on or after 2013 that met the following criteria were included: (1) Describe or evaluate a policy, program, or intervention or treatment at the health service delivery level for individuals with TBI and MHSU; (2) screen or diagnosis for TBI in a MHSU health service setting; or (3) screen or diagnosis for MHSU in a brain injury health service setting. <h3>Data Extraction</h3> A narrative synthesis was conducted using data extracted independently by one reviewer and peer-reviewed by a second reviewer. All articles were assessed for risk of bias independently by one reviewer using quality assessment tools and peer-reviewed by a second reviewer. <h3>Data Synthesis</h3> Fifty-nine articles were included, describing treatments (N=49), programs (N=4), or screening/diagnosis (N=7). These articles described clinical integrations at the micro- (N=38) and meso-levels (N=10), service integration at the micro- (N=6) and meso-levels (N=5), and functional integration at the meso-level (N=1). Seven articles reported on facilitators (e.g., cognitive accommodations in treatment plans) and two articles reported on barriers (e.g., lack of education on TBI and MHSU); six articles reported both barriers and facilitators. <h3>Conclusions</h3> Integrated TBI and MHSU care already exists across a range of levels and types. Given the finite and competing demands for healthcare resources, facilitators such as cognitive accommodations across treatment plans should be considered. Multidisciplinary teams should also be explored to provide opportunities for education among health professionals so they can be familiar with TBI and MHSU. <h3>Author(s) Disclosures</h3> None.

Chronicity of repeated blast traumatic brain injury associated increase in oxycodone seeking in rats

Numerous epidemiological studies have found co-morbidity between non-severe traumatic brain injury (TBI) and substance misuse in both civilian and military populations. Preclinical studies have also identified this relationship for some misused substances. We have previously demonstrated that repeated blast traumatic brain injury (rbTBI) increased oxycodone seeking without increasing oxycodone self-administration, suggesting that the neurological sequelae of traumatic brain injury can elevate opioid misuse liability. Here, we determined the chronicity of this effect by testing different durations of time between injury and oxycodone self-administration and durations of abstinence. We found that the subchronic (four weeks), but not the acute (three days) or chronic (four months) duration between injury and oxycodone self-administration was associated with increased drug seeking and re-acquisition of self-administration following a 10-day abstinence. Examination of other abstinence durations (two days, four weeks, or four months) revealed no effect of rbTBI on drug seeking at any of the abstinence durations tested. Together, these data indicate that there is a window of vulnerability after TBI when oxycodone self-administration is associated with elevated drug seeking and relapse-related behaviors.

Rhinocerebral Mucormycosis in Patients with Diabetes Mellitus After a New Coronavirus Infection (COVID-19): СT and MRI Patterns Data

Objective: to study the computed tomography (CT) and magnetic resonance imaging (MRI) manifestations of rhinocerebral mucormycosis (RCM) in patients with diabetes mellitus and new coronavirus infection, to develop attentive attitude of radiologists for early detection of this pathology, rapid surgery and followup examinations.Material and methods. Totally 53 head (facial skull, soft facial tissues and brain) CT and MRI studies were performed in 13 patients with RCM. The number of CT and MRI studies varied from 1 to 9 per one patient, depending on the severity of his condition and clinical indications; the follow-up period was 1–4 months. All patients received surgical aid; diagnosis was verified by microscopy of surgical samples of excised necrotic tissues. A detailed descriptive analysis of pathological changes on CT and MRI characterizing RCM was carried out. The sequence of pathological signs manifestations was described, the prevalence of the lesion was estimated for planning the scope of surgical intervention. A comparative analysis of the identified RCM signs with the literature data was performed.Results. Lesions of the nasal cavity and paranasal sinuses in RCM were found in 100% of our observations, with approximately equal single and bilateral lesions of 54% and 46%, respectively. Lesions of the perimaxillar fatty tissue and pterygoid fossa were determined in 77% of patients, unilateral orbital lesions – in 23%, superior orbital vein and cavernous sinus thrombosis – in 31%, facial soft tissue lesion – in 15.5%, intracranial spread through the perineural spaces – in 7.7%, internal carotid artery arteritis – in 15.5%. Brain substance and meninges involvement in the pathological process was observed in the form of cerebritis in 23% of patients and meningitis in 46%. The formation of brain abscess was noted in follow up examinations in 15.5% of patients, skull bones osteomyelitis was diagnosed in 46%. The mortality rate was 15%. In cases of long-term observation, the manifestations of pathological changes started from the nasal cavity, then spreaded in the perimaxillary adipose tissue and orbit, and were followed by the development of intracranial complications.Conclusion. The accumulated experience in identifying the combination of CT and MRI signs and patterns of RCM combined with clinical and anamnestic data allows to increase the alertness of clinicians and radiologists for earlier diagnosis and selection of the optimal volume of surgical intervention.

ОСОБЕННОСТИ ЛУЧЕВОЙ ДИАГНОСТИКИ КРОВОИЗЛИЯНИЙ В ОЧАГИ ПОРАЖЕНИЯ ГОЛОВНОГО МОЗГА ПРИ ОНКОГЕМАТОЛОГИЧЕСКОЙ ПАТОЛОГИИ. КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ

The acute myeloid leukemia (AML) is the malignant transformation and uncontrolled proliferation of abnormally differentiated, long-lived myeloid progenitor cells cause a large number of blast cells in the circulating blood and replacement of normal bone marrow with tumor cells, as well as damage to other organs and systems. Neurological disorders in AML diseases are among the secondary lesions of the nervous system. Morphologically, neuroleukemia is characterized by multifocal leukemic infiltrates and disorders of the myelination of nerve fibers. The formation of leukemic foci in the medulla leads to an increase in intracranial pressure, compression of cerebral and spinal structures, loss of functions of the affected area. In such situations, computed tomography of the brain may reveal lesions of the brain substance, leukemic infiltration of the meninges of the brain, intracranial hemorrhages, and cerebral infarctions.

Friedelin Attenuates Neuronal Dysfunction and Memory Impairment by Inhibition of the Activated JNK/NF-κB Signalling Pathway in Scopolamine-Induced Mice Model of Neurodegeneration.

Oxidative stress (OS) and c-Jun N-terminal kinase (JNK) are both key indicators implicated in neuro-inflammatory signalling pathways and their respective neurodegenerative diseases. Drugs targeting these factors can be considered as suitable candidates for treatment of neuronal dysfunction and memory impairment. The present study encompasses beneficial effects of a naturally occurring triterpenoid, friedelin, against scopolamine-induced oxidative stress and neurodegenerative pathologies in mice models. The treated animals were subjected to behavioural tests i.e., Y-maze and Morris water maze (MWM) for memory dysfunction. The underlying mechanism was determined via western blotting, antioxidant enzymes and lipid profile analyses. Molecular docking studies were carried out to predict the binding modes of friedelin in the binding pocket of p-JNK protein. The results reveal that scopolamine caused oxidative stress by (1) inhibiting catalase (CAT), peroxidase enzyme (POD), superoxide dismutase (SOD), and reduced glutathione enzyme (GSH); (2) the up-regulation of thiobarbituric acid reactive substances (TBARS) in mice brain; and (3) affecting the neuronal synapse (both pre- and post-synapse) followed by associated memory dysfunction. In contrast, friedelin administration not only abolished scopolamine-induced oxidative stress, glial cell activation, and neuro-inflammation but also inhibited p-JNK and NF-κB and their downstream signaling molecules. Moreover, friedelin administration improved neuronal synapse and reversed scopolamine-induced memory impairment accompanied by the inhibition of β-secretase enzyme (BACE-1) to halt amyloidogenic pathways of amyloid-β production. In summary, all of the results show that friedelin is a potent naturally isolated neuro-therapeutic agent to reverse scopolamine-induced neuropathology, which is characteristic of Alzheimer’s disease.

Nivolumab with Ipilimumab in the treatment of refractory hepatocellular carcinoma

HCC is considered refractory when it comes to progression during treatment with TKIs (sorafenib, lenvatinib). The combined immunotherapy of nivolumab with ipilimumab was studied in the one cohort of CheckMate-040 study, excluding immunotherapy-naive patients. The question of choosing an immunotherapy option in the presence of several options remains open. Like separate issue remains the prospect of using immunotherapeutic combinations after progression on immunotherapy. We present a long history of treatment of a patient with advanced HCC, which has been observed for 8 years at the Blokhin National Medical Research Center of Oncology. The example of this clinical observation shows the result of a multidisciplinary individual approach to the treatment of advanced HCC with the background of hepatitis C virus without liver cirrhosis (Child -Pugh A), stage BCLC-C. During this period of time, the patient received 5 lines of antitumor therapy, which were repeatedly supplemented with TACE procedures, radiation therapy and surgical treatment, with oligometastatic progression. The longest period of therapy without progression was recorded with the use of Nivolumab 240 mg in the 3rd line for 18 months, without clinically significant toxicity. The disease progressed with damage of the brain substance, one-stage microsurgical removal of metastases was performed, followed by EBRT. 4-line TKI therapy was not long-term. Due to the lack of a potential therapy option, it was recommended to resume therapy with anti-PD-1 with the addition of anti-CTLA-4, which gave its objective effect. Since November 2021 patient received 4 courses of Nivolumab 1 mg/kg + ipilimumab 3 mg/kg once every 3 weeks, and a partial effect was achieved (-42% according to RECIST 1.1). Then we performed nivolumab 240 mg IV every 2 weeks — which the patient continues to the present time.

Differential expression of serum extracellular vesicle microRNAs and analysis of target-gene pathways in major depressive disorder

Major depressive disorder (MDD) presents with both peripheral and central alterations, such that crosstalk between the periphery and the central nervous system could contribute to its aetio-pathophysiology. One putative mediating mechanism is circulating extracellular vesicles (EVs) and their microRNA (miRNA) cargo. In this study, we investigated differential expression of the serum EV miRNome in MDD patients versus controls with the aims of identifying potential EV miRNA biomarkers and downstream target gene pathways. miRNA-Sequencing was performed on serum EVs isolated from MDD patients (n = 42) and matched healthy Controls (n = 18). Differential expression analysis was conducted, followed by diagnostic power analysis of dysregulated EV miRNAs, and pathway analysis of their target genes. Of 1800 serum EV miRNAs detected consistently, 33 were differentially expressed in MDD and Control subjects, 17 up-regulated and 16 down-regulated. Receiver-operating characteristic analysis identified an up-regulated and a down-regulated panel of EV miRNAs, each with additive diagnostic power as a differential biomarker for MDD. Predicted target gene-pathways were significantly enriched with respect to brain function, signal transduction and substance dependence ontology. This study provides one of the first reports of dysregulation of the peripheral EV miRNome in MDD, including evidence for EV miRNAs as potential MDD biomarkers and identification of pathways via which they may contribute to MDD pathophysiology. Large-scale studies are required to confirm EV miRNome biomarker potential in MDD. Empirical evidence for involvement of the dysregulated EV miRNAs in the predicted target-gene pathways relevant to MDD pathophysiology is required. • About 1800 extracellular vesicle (EV) miRNAs identified in human serum samples. • Differential expression of 33 EV miRNAs in major depressive disorder (MDD) patients. • Panels of 4–6 EV miRNAs displayed MDD biomarker diagnostic power. • EV miRNA targets enriched in nervous system pathways underlying MDD pathophysiology.

МЕТАСТАТИЧЕСКОЕ ПОРАЖЕНИЕ ГОЛОВНОГО МОЗГА. ДИАГНОСТИКА И ЛЕЧЕНИЕ

The article provides an overview of the current literature on the diagnosis and treatment of second-ary (metastatic) damage to the brain substance.&#x0D; Over the past years, Russia has seen a high incidence of malignant neoplasms, with a clearly observed upward trend. In 2019, this figure was 376.3 per 100,000 population compared to 369.6 per 100,000 population in 2018 and 293.7 per 100,000 population in 2000. However, thanks to modern methods of diagnosis and treatment, the life span of patients suffering from malignant neo-plasms is significantly increased, and, as a result, the chance of “surviving” before the onset of a metastatic lesion of the brain substance increases. Today, this formidable complication of the tumor process occurs in approximately 8-10% of cancer patients, while in most of them they are symptomatic. In some nosological forms of malig-nant neoplasms (small cell lung cancer, melanoma), the frequency of brain metastasis can reach 80% or more.

The central nervous system involvement in listeria monocytogenes infection (clinical case)

Introduction. This report of Listeria monocytogenes infection with the involvment of central nervous system is important due to the increased frequency either in adults or children as well as the usually severe course and high mortality in generalized forms, especially with the CNS involvement. The demonstration of this clinical case, especialy the features of structural changes in the CNS with MRI in the disease’s dynamics, reflects the complexity of differential diagnosis and the evaluation of therapy effectiveness.Purpose of the study. To present a clinical case of CNS lesion in a 7-year-old child, the causative factor of which was listeria infection, with a detailed description of structural changes in the CNS using MRI studies.Material and methods. There is a clinical observation of a patient (child) with a diagnosis of listeriosis, secondary generalized form, extremely severe clinical course, with lesions of the central nervous system (meningoencephalitis). A series of magnetic resonance imaging studies of the brain in dynamics against the background of treatment are analyzed. Structural changes were assessed using multiparameter MRI of the brain using the following modes: T1-weighted, T2-weighted, Flair, T1-weighted with contrast, diffusionweighted and diffusion tensor imaging (DWI / DTI), susceptibility weighted imaging (SWI), MR perfusion, MR angiography.Results. The revealed structural changes in the brain during dynamic MRI examination, as well as their correlation with the data of anamnesis and clinical and laboratory data, made it possible to confirm meningoencephalitis, as well as to evaluate and make adjustments to the treatment.Conclusion. The described clinical case, the features of the course of the disease and MRI changes, suggest that dynamic MRI research is of great importance in identifying and assessing (including dynamics) structural changes in the brain substance in patients with neurological disorders in infectious diseases. The obtained data can be used by the attending physicians to assess and correct the ongoing therapy, to determine the required amount of rehabilitation.

Intellectual/developmental disabilities among people incarcerated in federal correctional facilities in Ontario, Canada: Examining prevalence, health and correctional characteristics.

There is little research with people who experience intellectual/developmental disabilities and imprisonment. The study linked health and correctional data to examine prevalence of intellectual/developmental disabilities and health and correctional characteristics among adults experiencing their first federal incarceration between 1 January 2002 and 31 December 2011 (n= 9278) and two non-incarcerated groups (n= 10,086,802). The prevalence of intellectual/developmental disabilities was 2.1% in the incarcerated group and 0.9% in the non-incarcerated group. Before incarceration, those with, versus without, intellectual/developmental disabilities were at greater risk of traumatic brain injury, mental illness, and substance use disorders. While incarcerated, those with intellectual/developmental disabilities were more likely to incur serious institutional disciplinary charges. Post-incarceration, persons with intellectual/developmental disabilities were at greater risk of emergency department visits, and psychiatric and acute hospitalizations, than the non-incarcerated groups. People with intellectual/developmental disabilities are overrepresented in Canadian federal correctional institutions. The authors offer strategies to support people prior to, during, and post-incarceration.

A systematic review on integrated care for traumatic brain injury, mental health, and substance use.

Traumatic brain injuries (TBI) and mental health or substance use disorders (MHSU) are global public health concerns due to their prevalence and impact on individuals and societies. However, care for individuals with TBI and MHSU remains fragmented with a lack of appropriate services and supports across the continuum of healthcare. This systematic review provided an evidence-based foundation to inform opportunities to mobilize and adapt existing resources to integrate care for individuals with TBI and MHSU by comprehensively summarizing existing integrated activities and reported barriers and facilitators to care integration. MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Sociological s, and Dissertations & Theses Global were independently reviewed by two reviewers based on pre-determined eligibility criteria. Data on the integration activity, level and type of integration, reported barriers and facilitators, and the strategies aligning with the World Health Organization’s (WHO) Framework on Integrated Person-Centred Care were extracted to form the basis for a narrative synthesis. Fifty-nine peer-reviewed articles were included, describing treatments (N = 49), programs (N = 4), or screening activities (N = 7). Studies discussing clinical integration at the micro- (N = 38) and meso- (N = 10) levels, service integration at the micro- (N = 6) and meso- (N = 5) levels, and functional integration at the meso-level (N = 1) were identified. A minority of articles reported on facilitators (e.g., cognitive accommodations in treatment plans; N = 7), barriers (e.g., lack of education on cognitive challenges associated with TBI; N = 2), or both (N = 6), related to integrating care. This review demonstrated that integrated TBI and MHSU care already exists across a range of levels and types. Given the finite and competing demands for healthcare resources, cognitive accommodations across treatment plans to facilitate integrated TBI and MHSU care should be considered. Multidisciplinary teams should also be explored to provide opportunities for education among health professionals so they can be familiar with TBI and MHSU.Trial registration: Prospero Registration: CRD42018108343.

DIAGNOSTIC VALUE OF MAGNETIC RESONANCE IMAGING IN ASSESSING CHANGES IN THE BRAIN SUBSTANCE AND CEREBRAL HEMODYNAMICS IN ACUTE CEREBROVASCULAR PATHOLOGYX

The relationship between the clinical picture of ischemic stroke and magnetic resonance imaging in assessing changes in the brain substance and cerebral hemodynamics was studied. It was stated that changes in the venous circulation of the brain are detected on magnetic resonance imaging and magnetic resonance angiography and show a stable reliable regular relationship with various states of the brain and carry important information about the organization of its blood supply and identification of the degree and severity of vascular damage to the brain.

DIAGNOSTIC VALUE OF MAGNETIC RESONANCE IMAGING IN ASSESSING CHANGES IN THE BRAIN SUBSTANCE AND CEREBRAL HEMODYNAMICS IN ACUTE CEREBROVASCULAR PATHOLOGY

The relationship between the clinical picture of ischemic stroke and magnetic resonance imaging in assessing changes in the brain substance and cerebral hemodynamics was studied. It was stated that changes in the venous circulation of the brain are detected on magnetic resonance imaging and magnetic resonance angiography and show a stable reliable regular relationship with various states of the brain and carry important information about the organization of its blood supply and identification of the degree and severity of vascular damage to the brain.

Critical and Creative Thinking and Photovoice: Strategies for Strengthening Participation and Inclusion.

Researchers, nonprofit organizations, and others have long used photovoice as a participatory action research method with vulnerable groups to depict, reflect on, and describe their realities, and advocate for change. Paulo Freire, whose scholarship is a foundation of photovoice, encouraged critical thinking in a popular education process to understand "the 'why' of things and facts." Creative thinking, a complementary concept that emerged in the field of education in the 1990s, involves, at its core, development, implementation, and communication of multiple original ideas. We provide a model of critical and creative thinking as an integrated process that generates knowledge as participants complete four key photovoice steps: (1) answer questions with a camera, (2) communicate in the group, (3) observe commonalities, and (4) communicate to power. We argue that each step involves teachable skills and provide practical, low-tech strategies that photovoice facilitators can use to enhance critical and creative thinking by any participant who finds it challenging to complete the four steps. Bringing a critical and creative thinking process to photovoice facilitation grounds the method in its education roots. It can enhance participation and inclusion of any vulnerable group, including people with cognitive and communication disorders due to acquired brain injury, mental illness, or substance use disorder for example. We suggest that use of the suggested strategies will result in an authentic, meaningful process that helps equalize power relationships, respects individuals as experts on their own lives, and increases the potential for data that prompt action.

Патогенез и клинические проявления ювенильной и сенильной форм болезни Фара (научный обзор)

В научном обзоре на основе анализа литературных источников представлен сложный патогенез развития неатеросклеротического симметричного обызвествления базальных ядер (болезнь Фара). Представлена оригинальная таблица основных причин кальцификации вещества головного мозга. Приведены основные направления в лечении описываемой патологии.

The adverse effect of modifiable dementia risk factors on cognition amplifies across the adult lifespan.

BackgroundReversible lifestyle behaviors (modifiable risk factors) can reduce dementia risk by 40%, but their prevalence and association with cognition throughout the adult lifespan is less well understood.MethodsThe associations between the number of modifiable risk factors for dementia (low education, hypertension, hearing loss, traumatic brain injury, alcohol or substance abuse, diabetes, smoking, and depression) and cognition were examined in an online sample (N = 22,117, ages 18–89).FindingsOlder adults (ages 66–89) had more risk factors than middle‐aged (ages 45–65) and younger adults (ages 18–44). Polynomial regression revealed that each additional risk factor was associated with lower cognitive performance (equivalent to 3 years of aging), with a larger association as age increased. People with no risk factors in their forties to seventies showed similar cognitive performance to people 10 or 20 years younger with many risk factors.InterpretationModifiable dementia risk factors amplify lifespan age differences in cognitive performance.

FEATURES OF FATAL INJURIES WHEN SHOOTING FROM CONVERTED AND REACTIVATED WEAPONS (TWO CASES FROM EXPERT PRACTICE)

Relevance. Gunshot injuries from converted and re-activated (remanufactured) weapons are increasingly common in expert practice. This is due to the free circulation of such weapons, which are not controlled by authorized bodies, no documents or registration are required for their acquisition, and their transfer to a combat state is a technologically simple and fast process.&#x0D; Objective: analysis of the nature and characteristics of injuries caused by shots from converted and reactivated weapons, based on data obtained in forensic medical expert practice in the study of corpses of victims with gunshot wounds to the head, as well as on the results of forensic ballistic examinations of firearms and ammunition for them.&#x0D; Materials and methods. Cases of forensic medical examination of gunshot wounds to the head when fired from converted and reactivated (recovered) hand-held firearms, resulting in the death of the victims.&#x0D; Results. The study found that the use of signal weapons (pistol "Stalker-M906" converted for firing pistol cartridges of 9 mm RA caliber) and recovered neutralized weapons (mass-dimensional model of a 7.62 mm Nagant revolver equipped with non-standard ammunition) when fired at point-blank and at close range led to fatal penetrating gunshot wounds, accompanied by perforated fractures of the skull bones, destruction of the brain substance and intracranial hemorrhages.&#x0D; Conclusions. The analyzed cases of gunshot wounds when fired from converted and reactivated weapons indicate the potential danger of causing fatal injuries to a person. Consequently, an important issue is to strengthen control over the circulation, use and storage of signal and neutralized weapons.

PECULIARITIES OF MICROCIRCULATORY BED VESSEL'S DENSITY CHANGE IN THE LOBULES OF THE WHITE RATS THYMUS IN NORM AND UNDER THE INFLUENCE OF SALTS OF HEAVY METALS WITHIN TWO MONTHS

From the three salts of heavy metals consumed by experimental white male rats of reproductive age in low concentrations for 2 months, the least toxic to the body is an aqueous solution of FeSO4 · 7H2O (iron sulphate) at a dose of 0.5 mg / dm3. The most toxic is an aqueous solution of ZnSO4 · 7H2O (zinc salt of sulfuric acid) at a dose of 1,505 mg / dm3, the use of which resulted in an increase in all vessels of the microcirculatory tract in both cortex and medulla of the lobules of thymus compared to the control group. The density of arterioles in the cortex increased 3.3 times, the density of venules - 2 times, the density of capillaries - 1.5 times; in the brain substance there is also a 2-fold increase in the density of arterioles, the density of venules - 1.2 times, the density of capillaries - 2.5 times compared with the control group of animals. In experimental male rats consuming aqueous solutions - CuSO4 · 5H2O at a dose of 0.247 mg / dm3, the density of arterioles and venules in the cortex of the thymus almost did not change, and the density of capillaries, compared with the control group, increased 1.5 times in medulla of thymus, compared with the control group, the density of arterioles increased 1.7 times, the density of venules increased 1.2 times, and the density of capillaries increased 1.6 times.

Metabolomic and pharmacologic analyses of brain substances associated with sleep pressure in mice

Sleep pressure, the driving force of the homeostatic sleep regulation, is accumulated during wakefulness and dissipated during sleep. Sleep deprivation (SD) has been used as a method to acutely increase animal’s sleep pressure for investigating the molecular changes under high sleep pressure. However, SD induces changes not only reflecting increased sleep pressure but also inevitable stresses and prolonged wake state itself. The Sik3Sleepy mutant mice (Sleepy) exhibit constitutively high sleep pressure despite sleeping longer, and have been useful as a model of increased sleep pressure. Here we conducted a cross-comparison of brain metabolomic profiles between SD versus ad lib slept mice, as well as Sleepy mutant versus littermate wild-type mice. Targeted metabolome analyses of whole brains quantified 203 metabolites in total, of which 43 metabolites showed significant changes in SD, whereas three did in Sleepy mutant mice. The large difference in the number of differential metabolites highlighted limitations of SD as methodology. The cross-comparison revealed that a decrease in betaine and an increase in imidazole dipeptides are associated with high sleep pressure in both models. These metabolites may be novel markers of sleep pressure at the whole-brain level. Furthermore, we found that intracerebroventricular injection of imidazole dipeptides increased subsequent NREM sleep time, suggesting the possibility that imidazole dipeptides may participate in the regulation of sleep in mice.