Study of Morphofunctional Parameters of Blood Cells in Ischemic Stroke Using a Genome-wide Research

Biomarkers can play many useful roles in modern neurology. Early diagnosis and immediate therapy are important factors for reducing the degree of brain tissue damage in ischemic stroke, reduces the risk of death from stroke. In the current study, apolipoprotein CIII (ApoCIII), a biomarker of ischemic stroke, was found.

Correlation of Cerebral and Subcutaneous Glycerol in Severe Traumatic Brain Injury and Association with Tissue Damage

Background This study is a substudy of a prospective consecutive double-blinded randomized study on the effect of prostacyclin in severe traumatic brain injury (sTBI). The aims of the present study were to investigate whether there was a correlation between brain and subcutaneous glycerol levels and whether the ratio of interstitial glycerol in the brain and subcutaneous tissue (glycerolbrain/sc) was associated with tissue damage in the brain, measured by using the Rotterdam score, S-100B, neuron-specific enolase (NSE), the Injury Severity Score (ISS), the Acute Physiology and Chronic Health Evaluation Score (APACHE II), and trauma type. A potential association with clinical outcome was explored. Methods Patients with sTBI aged 15–70 years presenting with a Glasgow Coma Scale Score ≤ 8 were included. Brain and subcutaneous adipose tissue glycerol levels were measured through microdialysis in 48 patients, of whom 42 had complete data for analysis. Brain tissue damage was also evaluated by using the Rotterdam classification of brain computed tomography scans and the biochemical biomarkers S-100B and NSE. Results In 60% of the patients, a positive relationship in glycerolbrain/sc was observed. Patients with a positive correlation of glycerolbrain/sc had slightly higher brain glycerol levels compared with the group with a negative correlation. There was no significant association between the computed tomography Rotterdam score and glycerolbrain/sc. S-100B and NSE were associated with the profile of glycerolbrain/sc. Our results cannot be explained by the general severity of the trauma as measured by using the Injury Severity Score or Acute Physiology and Chronic Health Evaluation Score. Conclusions We have shown that peripheral glycerol may flux into the brain. This effect is associated with worse brain tissue damage. This flux complicates the interpretation of brain interstitial glycerol levels. We remind the clinicians that a damaged blood–brain barrier, as seen in sTBI, may alter the concentrations of various substances, including glycerol in the brain. Awareness of this is important in the interpretation of the data bedside as well in research.

Microglia Phenotype and Intracerebral Hemorrhage: A Balance of Yin and Yang

Intracerebral hemorrhage (ICH) features extremely high rates of morbidity and mortality, with no specific and effective therapy. And local inflammation caused by the over-activated immune cells seriously damages the recovery of neurological function after ICH. Fortunately, immune intervention to microglia has provided new methods and ideas for ICH treatment. Microglia, as the resident immune cells in the brain, play vital roles in both tissue damage and repair processes after ICH. The perihematomal activated microglia not only arouse acute inflammatory responses, oxidative stress, excitotoxicity, and cytotoxicity to cause neuron death, but also show another phenotype that inhibit inflammation, clear hematoma and promote tissue regeneration. The proportion of microglia phenotypes determines the progression of brain tissue damage or repair after ICH. Therefore, microglia may be a promising and imperative therapeutic target for ICH. In this review, we discuss the dual functions of microglia in the brain after an ICH from immunological perspective, elaborate on the activation mechanism of perihematomal microglia, and summarize related therapeutic drugs researches.

Transcranial focused ultrasound modulates cortical and thalamic motor activity in awake sheep

Transcranial application of pulsed low-intensity focused ultrasound (FUS) modulates the excitability of region-specific brain areas, and anesthetic confounders on brain activity warrant the evaluation of the technique in awake animals. We examined the neuromodulatory effects of FUS in unanesthetized sheep by developing a custom-fit headgear capable of reproducibly placing an acoustic focus on the unilateral motor cortex (M1) and corresponding thalamic area. The efferent responses to sonication, based on the acoustic parameters previously identified in anesthetized sheep, were measured using electromyography (EMG) from both hind limbs across three experimental conditions: on-target sonication, off-target sonication, and without sonication. Excitatory sonication yielded greater amplitude of EMG signals obtained from the hind limb contralateral to sonication than that from the ipsilateral limb. Spurious appearance of motion-related EMG signals limited the amount of analyzed data (~ 10% selection of acquired data) during excitatory sonication, and the averaged EMG response rates elicited by the M1 and thalamic stimulations were 7.5 ± 1.4% and 6.7 ± 1.5%, respectively. Suppressive sonication, while sheep walked on the treadmill, temporarily reduced the EMG amplitude from the limb contralateral to sonication. No significant change was found in the EMG amplitudes during the off-target sonication. Behavioral observation throughout the study and histological analysis showed no sign of brain tissue damage caused by the acoustic stimulation. Marginal response rates observed during excitatory sonication call for technical refinement to reduce motion artifacts during EMG acquisitions as well as acoustic aberration correction schemes to improve spatial accuracy of sonication. Yet, our results indicate that low-intensity FUS modulated the excitability of regional brain tissues reversibly and safely in awake sheep, supporting its potential in theragnostic applications.

Influence of von Willebrand factor on common pathophysiological mechanisms of cerebrovascular diseases and multiple sclerosis

Endothelial dysfunction is a universal pathological mechanism underlying or contributing to the development/progression of many diseases, including cerebrovascular disease and multiple sclerosis. Von Willebrand factor is a multimeric glycoprotein synthesized by endothelial cells and megakaryocytes that participates in a range of physiological and pathological processes, including primary hemostasis and coagulation. It also regulates secretion and transport of a variety of molecules, exerts a proinflammatory effect, modulates angiogenesis and smooth muscle mitotic activity, influences atherogenesis. In this review, we discuss the synthesis, secretion, and regulation of the von Willebrand factor within the context of endothelial dysfunction and other common mechanisms that play a significant role in brain tissue damage in cerebrovascular diseases and multiple sclerosis.

Nitric Oxide-Dependent Pathways as Critical Factors in the Consequences and Recovery after Brain Ischemic Hypoxia

Brain ischemia is one of the leading causes of disability and mortality worldwide. Nitric oxide (NO•), a molecule that is involved in the regulation of proper blood flow, vasodilation, neuronal and glial activity constitutes the crucial factor that contributes to the development of pathological changes after stroke. One of the early consequences of a sudden interruption in the cerebral blood flow is the massive production of reactive oxygen and nitrogen species (ROS/RNS) in neurons due to NO• synthase uncoupling, which leads to neurotoxicity. Progression of apoptotic or necrotic neuronal damage activates reactive astrocytes and attracts microglia or lymphocytes to migrate to place of inflammation. Those inflammatory cells start to produce large amounts of inflammatory proteins, including pathological, inducible form of NOS (iNOS), which generates nitrosative stress that further contributes to brain tissue damage, forming vicious circle of detrimental processes in the late stage of ischemia. S-nitrosylation, hypoxia-inducible factor 1α (HIF-1α) and HIF-1α-dependent genes activated in reactive astrocytes play essential roles in this process. The review summarizes the roles of NO•-dependent pathways in the early and late aftermath of stroke and treatments based on the stimulation or inhibition of particular NO• synthases and the stabilization of HIF-1α activity.

Use of Antioxidants for the Neuro-Therapeutic Management of COVID-19

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is an emergent infectious disease that has caused millions of deaths throughout the world. COVID-19 infection’s main symptoms are fever, cough, fatigue, and neurological manifestations such as headache, myalgias, anosmia, ageusia, impaired consciousness, seizures, and even neuromuscular junctions’ disorders. In addition, it is known that this disease causes a series of systemic complications such as adverse respiratory distress syndrome, cardiac injury, acute kidney injury, and liver dysfunction. Due to the neurological symptoms associated with COVID-19, damage in the central nervous system has been suggested as well as the neuroinvasive potential of SARS-CoV-2. It is known that CoV infections are associated with an inflammation process related to the imbalance of the antioxidant system; cellular changes caused by oxidative stress contribute to brain tissue damage. Although anti-COVID-19 vaccines are under development, there is no specific treatment for COVID-19 and its clinical manifestations and complications; only supportive treatments with immunomodulators, anti-vascular endothelial growth factors, modulating drugs, statins, or nutritional supplements have been used. In the present work, we analyzed the potential of antioxidants as adjuvants for the treatment of COVID-19 and specifically their possible role in preventing or decreasing the neurological manifestations and neurological complications present in the disease.

Evaluation of Neurological Complications in Hospitalized COVID-19 Patients: A Cross-Sectional Study 2020

Objective: The coronavirus (COVID-19) has been spreading around the world since December 2019. Neurological symptoms have been reported as a part of the clinical spectrum of the disease. This study aimed to determine the frequency of neurological complications in hospitalized patients with COVID-19.Methods: Electronic medical records in the hospital information system, laboratory findings, and radiological examinations were evaluated for all patients with laboratory-confirmed SARS-CoV-2 infection. The cases were referred to Shahid Beheshti Hospital affiliated to Hamadan University of Medical Sciences from February 20, 2020 to the end of the same year.Results: A total of 477 hospitalized COVID-19 patients were included in the analyses. Based on our results, 105 (22.02%) patients showed neurological manifestations. Ischemic stroke, decreased consciousness, and headache were the most frequent reported neurological symptoms with the rate of 34 (7.13%), 28 (5.88%), and13 (2.72%), respectively. Moreover, 54 (51.43%) cases were male, and the vast majority of the patients (66; 62.86%) had more than 60 years of age. Conclusions: SARS-CoV-2 may involve nervous system and cause brain tissue damage. The findings of this study provide more information on coronavirus disease, contributing to effective interventions for the control of the disease