Ischemic Brain Infarction Research Articles

The Ethanolic Extract of Polygala paniculata L. Blocks Panx1 Channels and Reduces Ischemic Brain Infarct in a Dose- and Sex-Dependent Way.

Polygala paniculata L. is a native plant from tropical America. The therapeutic potential of the hydroalcoholic extract of P. paniculata (HEPp) has been scientifically explored due to folk medicine reports on its action against several afflictions. HEPp contains several bioactive molecules with neuroprotective activities, making it a promising candidate for stroke treatment. This study used electrophysiological, biochemical, and in vivo experiments to evaluate the molecular mechanisms underlying HEPp as a neuroprotective therapy for stroke targeting Pannexin-1 (Panx1). Panx1 is a non-selective channel that opens during ischemia and contributes to neuronal death. HEPp was not toxic to cortical neurons and pre-treatment with the extract reduced neuronal death promoted by oxygen and glucose deprivation in a dose-dependent manner. Additionally, HEPp blocked Panx1 currents in a dose-dependent manner and the effect, which was shown to be partially due to rutin. Animals submitted to photothrombosis and post-treated with HEPp had reduced infarct volume, and the effective dose was lower in males (1mg/kg) than in females (10mg/kg). On the other hand, in Panx1 KD mice (50% Panx1 levels), the acute treatment reduced the infarct volume only in males. Upon chronic treatment with HEPp, a reduction in Panx1 protein levels was observed. The current study provides reliable evidence of the neuroprotective properties of HEPp in both in vitro and in vivo models of stroke. The underlying mechanism involves, at least in part, the inhibition of Panx1 channel function and possibly downregulation of protein levels, suppressing the secondary events that lead to apoptosis and inflammation.

Design, synthesis and neuroprotective biological evaluation of novel HDAC6 inhibitors incorporating benzothiadiazinyl systems as cap groups.

Histone deacetylase 6 (HDAC6), as the key regulatory enzyme, plays an important role in the development of the nervous system. More and more studies indicate that HDAC6 has become a promising therapeutic target for CNS diseases. Herein we designed and synthesized a series of novel HDAC6 inhibitors with benzothiadiazinyl systems as cap groups and evaluated their activity invitro and invivo. Among them, compound 3 exhibited superior selective inhibitory activity against HDAC6 (IC50 = 5.1 nM, about 30-fold selectivity over HDAC1). The results of docking showed that compound 3 can interact well with the key amino acid residues of HDAC6. Compound 3 showed lower cytotoxicity (20 μM to SH-SY5Y cells, inhibition rate = 25.75%) and better neuroprotective activity against L-glutamate-induced SH-SY5Y cell injury model invitro. Meanwhile, compound 3 exhibited weak cardiotoxicity (10 μM hERG inhibition rate = 17.35%) and possess good druggability properties. Especially, compound 3 could significantly reduce cerebral infarction from 49.87% to 32.18%, and similar with butylphthalide in MCAO model, indicating potential clinical application prospects for alleviating ischemic stroke-induced brain infarction.

Microvascular Network Remodeling in the Ischemic Mouse Brain Defined by Light Sheet Microscopy.

Until now, the analysis of microvascular networks in the reperfused ischemic brain has been limited due to tissue transparency challenges. Using light sheet microscopy, we assessed microvascular network remodeling in the striatum from 3 hours to 56 days post-ischemia in 2 mouse models of transient middle cerebral artery occlusion lasting 20 or 40 minutes, resulting in mild ischemic brain injury or brain infarction, respectively. We also examined the effect of a clinically applicable S1P (sphingosine-1-phosphate) analog, FTY720 (fingolimod), on microvascular network remodeling. Over 56 days, we observed progressive microvascular degeneration in the reperfused striatum, that is, the lesion core, which was followed by robust angiogenesis after mild ischemic injury induced by 20-minute middle cerebral artery occlusion. However, more severe ischemic injury elicited by 40-minute middle cerebral artery occlusion resulted in incomplete microvascular remodeling. In both cases, microvascular networks did not return to their preischemic state but displayed a chronically altered pattern characterized by higher branching point density, shorter branches, higher unconnected branch density, and lower tortuosity, indicating enhanced network connectivity. FTY720 effectively increased microvascular length density, branching point density, and volume density in both models, indicating an angiogenic effect of this drug. Utilizing light sheet microscopy together with automated image analysis, we characterized microvascular remodeling in the ischemic lesion core in unprecedented detail. This technology will significantly advance our understanding of microvascular restorative processes and pave the way for novel treatment developments in the stroke field.

In-Hospital Acute Ischemic Stroke Case Fatality: Experience from a University Hospital in Bogota, Colombia (2018-2019).

Introduction Until 2020, stroke was the second cause of death in Colombia and worldwide. In-hospital case fatality accounts for the majority of deaths. Multiple risk factors for in-hospital mortality have been described in the stroke population and their recognition could reduce stroke-related death. Aims To describe a single center experience of in-hospital acute ischemic stroke case fatality and its risk factors. Methodology Single center, retrospective, cross-sectional study between august 2018 and august 2019. Admitted consecutive patients with acute ischemic stroke brain infarct type were included. Admission sociodemographic, clinical, laboratory and imaging studies variables were drawn out. Quantitative variables were summarized as means, medians and interquartile ranges. Bivariate analysis was used to evaluate associations of in-hospital stroke case fatality and imputed variables. Results 402 stroke brain infarct type patients were included, mean age 73,28 years (SD±14,53), 50,4% men. Prevalent vascular risks factors were hypertension (70,90%), diabetes mellitus type 2 (24,13%) and previous stroke (20,90%). There were 13 (3,2%) in-hospital case fatalities. Mean time from admission to death was 11.38 days (SD±10,8). Lower hemoglobin levels (p=0.002), lower total, LDL and HDL serum cholesterol levels (p=0.02), internal carotid artery stenosis >50% by duplex ultrasound (p=0.01) and stroke severity as measured by NIHSS score (p<0,0001) showed association with in-hospital stroke case fatality. Conclusions NIHSS score, hemoglobin level, and cholesterol (total, LDL, HDL) levels upon admission may be used by clinicians to make the appropriate early transfer decisions to facilities with the capacity to offer advance in-hospital stroke care. The cholesterol paradox in acute stroke fatality warrants further studies.

Distribution of Nicotinamide Mononucleotide after Intravenous Injection in Normal and Ischemic Stroke Mice.

This study determined for the first time the distribution of intravenous nicotinamide mononucleotide (NMN) and its metabolite nicotinamide adenine dinucleotide (NAD) in normal and ischemic stroke mice, examined the therapeutic effect of NMN on ischemic brain infarction, and evaluated acute toxicity of NMN after intravenous injection of NMN. NMN and NAD levels were determined using ultra-high-performance liquid chromatography tandem mass spectrometry in biological samples from mice with or without middle cerebral artery occlusion (MCAO) at different time points post intravenous NMN injection (300 mg/kg). Brain infarction was evaluated 24 h post-MCAO. 2 g/kg NMN was used in the acute toxicity test. Under either normal or MCAO conditions, serum NMN levels sharply increased after intravenous NMN administration and then decreased rapidly within 15 min, while serum NAD levels remained unchanged during 30 min observation. Both substances displayed tissue accumulation over time and stored faster under MCAO conditions, with kidney having the highest concentrations. Particularly, NMN accumulated earlier than NAD in the brain. Moreover, NMN reduced cerebral infarction at 24 h post-MCAO. No acute toxicity was observed for 14 days. NRK1 and SLC12A8 involved in two pathways of NMN uptake exhibited the highest expressions in kidney and colon, respectively, among 11 different tissues. NMN distributes to various tissues after intravenous injection and has the ability to enter the brain to boost NAD levels, and exhibits safety and therapeutic effect on acute ischemic stroke injury. High renal distribution of NMN indicates its importance in the kidney.

Near infrared spectroscopy detection of hemispheric cerebral ischemia following middle cerebral artery occlusion in rats

Timely and sensitive in vivo estimation of ischemic stroke-induced brain infarction are necessary to guide diagnosis and evaluation of treatments’ efficacy. The gold standard for estimation of the cerebral infarction volume is magnetic resonance imaging (MRI), which is expensive and not readily accessible. Measuring regional cerebral blood flow (rCBF) with Laser Doppler flowmetry (LDF) is the status quo for confirming reduced blood flow in experimental ischemic stroke models. However, rCBF reduction following cerebral artery occlusion often does not correlate with subsequent infarct volume. In the present study, we employed the continuous-wave near infrared spectroscopy (NIRS) technique to monitor cerebral oxygenation during 90 min of the intraluminal middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats (n = 8, male). The NIRS device consisted of a controller module and an optical sensor with two LED light sources and two photodiodes making up two parallel channels for monitoring left and right cerebral hemispheres. Optical intensity measurements were converted to deoxyhemoglobin (Hb) and oxyhemoglobin (HbO2) changes relative to a 2-min window prior to MCAO. Area under the curve (auc) for Hb and HbO2 was calculated for the 90-min occlusion period for each hemisphere (ipsilateral and contralateral). To obtain a measure of total ischemia, auc of the contralateral side was subtracted from the ipsilateral side resulting in ΔHb and ΔHbO2 parameters. Infarct volume (IV) was calculated by triphenyl tetrazolium chloride (TTC) staining at 24h reperfusion. Results showed a significant negative correlation (r = −0.81, p = 0.03) between ΔHb and infarct volume. In conclusion, our results show feasibility of using a noninvasive optical imaging instrument, namely NIRS, in monitoring cerebral ischemia in a rodent stroke model. This cost-effective, non-invasive technique may improve the rigor of experimental models of ischemic stroke by enabling in vivo longitudinal assessment of cerebral oxygenation and ischemic injury.

TREATMENT OF ASTHMA MIGHT HAVE DELAYED END-ORGAN DAMAGE IN THE PATIENT WITH LYMPHOCYTIC HYPEREOSINOPHILIC SYNDROME

<h3>Introduction</h3> Hypereosinophilic syndrome (HES) is characterized by an absolute eosinophil count (AEC) > 1,500 and organ damage or dysfunction attributable to tissue eosinophilia. <h3>Case Description</h3> This 71-year-old patient with a 12-year history of asthma was treated with inhaled and variable daily doses of oral corticosteroids for four years. Without the risk factors for cardiovascular disease, he suddenly developed stroke symptoms. His brain MRI revealed multiple scattered patchy foci of acute cortical matter ischemia, and he was diagnosed with an acute cerebrovascular accident. He also had elevated troponin and underwent cardiac catheterization with stent placement to a proximal LAD and mid-LAD lesion. Four months later, he came for an allergy evaluation because of "elevated white cells" and "food allergy." However, he had an increased AEC of 3,800 and clinically irrelevant IgE to the tolerated foods. His medical record revealed that over the last four years, his AEC fluctuated between 374 and 8,730. Therefore, we initiated an evaluation for suspected HES, eosinophilic granulomatosis with polyangiitis, and, less likely, parasitoses. Molecular studies revealed a clonal population of lymphocytes with T-cell receptor gene γ and β rearrangement consistent with a diagnosis of lymphoid variant HES. Other laboratory findings are in figure 1. <h3>Discussion</h3> A common occurrence of eosinophilia in the patients with asthma might lower the index of suspicion of HES. However, this patient's very high AEC should have prompted an investigation earlier. His HES presented as multifocal ischemic brain and cardiac infarcts. This presentation was likely delayed by treating the patient's asthma with systemic corticosteroids.

Self-reported sleepiness associates with greater brain and cortical volume and lower prevalence of ischemic covert brain infarcts in a community sample.

We evaluated if self-reported sleepiness was associated with neuroimaging markers of brain aging and ischemic damage in a large community-based sample. Participants from the Framingham Heart Study Offspring cohort (n = 468, 62.5 ± 8.7 years old, 49.6%M) free of dementia, stroke, and neurological diseases, completed sleep questionnaires and polysomnography followed by magnetic resonance imaging (MRI), 3 years later on average. We used linear and logistic regression models to evaluate the associations between Epworth Sleepiness Scale (ESS) scores and total brain, cortical and subcortical gray matter, and white matter hyperintensities volumes, and the presence of covert brain infarcts. Higher sleepiness scores were associated with larger total brain volume, greater cortical gray matter volume, and a lower prevalence of covert brain infarcts, even when adjusting for a large array of potential confounders, including demographics, sleep profiles and disorders, organic health diseases, and proxies for daytime cognitive and physical activities. Interactions indicated that more sleepiness was associated with larger cortical gray matter volume in men only and in APOE ε4 noncarriers, whereas a trend for smaller cortical gray matter volume was observed in carriers. In longitudinal analyses, those with stable excessive daytime sleepiness over time had greater total brain and cortical gray matter volumes, whereas baseline sleepiness scores were not associated with subsequent atrophy or cognitive decline. Our findings suggest that sleepiness is not necessarily a marker of poor brain health when not explained by diseases or sleep debt and sleep disorders. Rather, sleepiness could be a marker of preserved sleep-regulatory processes and brain health in some cases.

Practical methods for segmentation and calculation of brain volume and intracranial volume: a guide and comparison.

Accurate segmentation and calculation of total brain volume (BV) and intracranial volume (ICV) (further-volumetry) may serve various clinical tasks and research studies in neuroscience. Manual segmentation is extremely time consuming. There is a relative lack of published broad recommendations and comparisons of tools for automated volumetry, especially for users without expertise in computer science, for settings with limited resources, and when neuroimaging quality is suboptimal due to clinical circumstances. Our objective is to decrease the barrier to entry for research and clinical groups to perform volumetric cranial imaging analysis using free and reliable software tools. Automated volumetry from computed tomography (CT)/magnetic resonance imaging (MRI) scans was accomplished using 3D Slicer (v. 4.11.0), FreeSurfer (v. 7.1.1), and volBrain (v. 1.0) in a cohort of 39 patients with ischemic middle cerebral artery territory brain infarcts in the acute stage. Visual inspection for accuracy was also performed. Statistical analysis included coefficient of determination (R2) and Bland-Altman (B-A) plots. A multifaceted comparison between 3D Slicer, FreeSurfer, and volBrain from practical user perspective was performed to compile a list of distinguishing features. BV: FreeSurfer, 3D Slicer, and volBrain provide similar estimations when high quality T1-MRI scans with 1 mm slices (3D scans) are available, whereas 3 mm and thicker slices (2D scans) introduce a dispersion in results. ICV: the most accurate volumetry is provided by 3D Slicer using CT scans. volBrain uses T1-MRIs and also provides good results which agree with 3D Slicer. Both of these methods may be more trustworthy than T1 MRI-derived FreeSurfer calculations. All three studied tools of automated intracranial and brain volumetry-3D Slicer, FreeSurfer, and volBrain-are free, reliable, require no complex programming, but still have certain limitations and significant differences. Based on our investigation findings, the readers should be able to select the right volumetry tool and neuroimaging study, and then follow provided step-by-step instructions to accomplish specific volumetry tasks.

Brain-associated innate leukocytes display diverse inflammatory states following experimental stroke.

Previous studies investigating innate leukocyte recruitment into the brain after cerebral ischemia have shown conflicting results. Using distinct cell surface and intracellular markers, the current study evaluated the contributions of innate immune cells to the poststroke brain following 1‐h middle cerebral artery occlusion (tMCAO) or permanent MCAO (pMCAO), and assessed whether these cells ascribed to an inflammatory state. Moreover, we examined whether there is evidence for leukocyte infiltration into the contralateral (CL) hemisphere despite the absence of stroke infarct. We observed the recruitment of peripheral neutrophils, monocytes and macrophages into the hemisphere ipsilateral (IL) to the ischemic brain infarct at 24 and 96 h following both tMCAO and pMCAO. In addition, we found evidence of increased leukocyte recruitment to the CL hemisphere but to a lesser extent than the IL hemisphere after stroke. Robust production of intracellular cytokines in the innate immune cell types examined was most evident at 24 h after pMCAO. Specifically, brain‐associated neutrophils, monocytes and macrophages demonstrated stroke‐induced production of tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐1β, while only monocytes and macrophages exhibit a significant expression of arginase 1 (Arg1) after stroke. At 96 h after stroke, brain‐resident microglia demonstrated production of TNF‐α and IL‐1β following both tMCAO and pMCAO. At this later timepoint, neutrophils displayed TNF‐α production and brain‐associated macrophages exhibited elevation of IL‐1β and Arg1 after tMCAO. Further, pMCAO induced significant expression of Arg1 and IL‐1β in monocytes and macrophages at 96 h, respectively. These results revealed that brain‐associated innate immune cells display various stroke‐induced inflammatory states that are dependent on the experimental stroke setting.

The Impact of Genetic Polymorphisms in Glutamate-Cysteine Ligase, a Key Enzyme of Glutathione Biosynthesis, on Ischemic Stroke Risk and Brain Infarct Size.

The purpose of this pilot study was to explore whether polymorphisms in genes encoding the catalytic (GCLC) and modifier (GCLM) subunits of glutamate-cysteine ligase, a rate-limiting enzyme in glutathione synthesis, play a role in the development of ischemic stroke (IS) and the extent of brain damage. A total of 1288 unrelated Russians, including 600 IS patients and 688 age- and sex-matched healthy subjects, were enrolled for the study. Nine common single nucleotide polymorphisms (SNPs) of the GCLC and GCLM genes were genotyped using the MassArray-4 system. SNP rs2301022 of GCLM was strongly associated with a decreased risk of ischemic stroke regardless of sex and age (OR = 0.39, 95%CI 0.24–0.62, p < 0.0001). Two common haplotypes of GCLM possessed protective effects against ischemic stroke risk (p < 0.01), but exclusively in nonsmoker patients. Infarct size was increased by polymorphisms rs636933 and rs761142 of GCLC. The mbmdr method enabled identifying epistatic interactions of GCLC and GCLM gene polymorphisms with known IS susceptibility genes that, along with environmental risk factors, jointly contribute to the disease risk and brain infarct size. Understanding the impact of genes and environmental factors on glutathione metabolism will allow the development of effective strategies for the treatment of ischemic stroke and disease prevention.

Hsa-miR-518-5p/hsa-miR-3135b Regulates the REL/SOD2 Pathway in Ischemic Cerebral Infarction.

ObjectivesIschemic cerebral infarction (ICI) is a fatal neurovascular disorder. A bioinformatics approach based on single-cell and bulk RNA-seq analyses was applied to investigate the pathways and genes involved in ICI and study the expression profile of these genes.MethodsFirst, the aberrantly regulated “small-molecule ribonucleic acids” [microRNA (miRNAs)] and messenger RNAs (mRNAs) were analyzed using transcriptome data from the ischemic brain infarction dataset of the Gene Expression Omnibus (GEO) database. In mouse cerebrovascular monocytes, the single-cell regulatory network inference and clustering (SCENIC) workflow was used to identify key transcription factors (TFs). Then, the two miRNA-TF-mRNA interaction networks were constructed. Moreover, the molecular complex detection (MCODE) extracted the core sub-networks and identified the important TFs within these sub-networks. Finally, whole blood samples were collected for validation of the expression of critical molecules in ICI.ResultsWe identified four cell types and 266 regulons in mouse cerebrovascular monocytes using SCENIC analysis. Moreover, 112 differently expressed miRNAs and 3,780 differentially expressed mRNAs were identified. We discovered potential biomarkers in ICI by building a miRNA-TF-mRNA interaction network. The hsa-miR-518-5p/hsa-miR-3135b/REL/SOD2 was found to play a potential role in ICI progression. The expression of REL and superoxide dismutase 2 (SOD2) was significantly elevated in the ICI group in the clinical cohort (P < 0.05). Furthermore, a REL expression was elevated in endothelial cells and fibroblasts at the single-cell level, indicating that REL is a cell-specific regulon. Functional enrichment analyses revealed that REL is primarily engaged in neurotransmitter activity and oxidative phosphorylation.ConclusionsOur research uncovered novel biomarkers for ICI of neurovascular disease. The hsa-miR-518-5p/hsa-miR-3135b may regulate the REL/SOD2 pathway in ICI progression.

Značaj multidetektorske kompjuterizovane tomografije u otkrivanju, praćenju i izboru terapije kod akutnog moždanog udara

Introduction: A stroke is a sudden, focal nonconvulsive neurological dysfunction which occurs due to vascular damage. Aim: The aim of the study was monitoring all patients who reported to the Emergency Center due to some neurological deficit, within a particular period of time. Materials and methods: For a period of one month, we monitored 123 patients who were admitted to the Department of Emergency Diagnostics with some form of neurological deficit and who underwent a native computed tomography (CT) scan and/or angiographic examination of the endocranium. All examinations were performed with the GE BrightSpeed 16 Slice CT scanner (USA). After initial native CT diagnostics, depending on the finding, the examination was either stopped, or the contrast dye was administered and postcontrast examination was performed or CT angiography was carried out. Results: Most of the patients with vascular neurological deficit were between 50 and 59 years old, while a smaller number of patients was registered in the age group of persons younger than 40 years. Most of the female patients were in the 50 - 59 age group, while most of the male patients were between 40 and 49 years old. Of the 94 patients who developed stroke, 78 (83%) patients had ischemic stroke, while 16 (17%) patients suffered hemorrhagic stroke. There is no statistically significant difference in the occurrence of intracerebral hemorrhage and subarachnoid hemorrhage between the sexes. The localization of ischemic brain infarction was in the vascular territory of the anterior cerebral artery (ACA) - 3.2% of the cases, the middle cerebral artery (MCA) - in 38.9% of the cases, the internal carotid artery (ICA) - in 8.4% of the patients, the basilar artery (BA) - in 13.7% of the cases, the posterior cerebral artery (PCA) - in 7.4% of the patients, the vertebral artery (VA) - 9.5% of the cases, and the supratentorial watershed areas of arterial irrigation - in 11.7% of the patients. Conclusion: Native CT examination is the golden standard for the triage of patients with acute stroke. The advantages of using a CT scan in the assessment of patients with acute stroke are that it is practical, precise, quick and available. CT imaging has prognostic value as well, as it can predict the response to the administered thrombolytic therapy.

TO DEVELOP FORENSIC CRITERIA FOR THE DIFFERENTIAL DIAGNOSIS OF INTRACEREBRAL HEMORRHAGE OF TRAUMATIC AND NON-TRAUMATIC ORIGIN USING MUELLER-MATRIX MICROSCOPY OF LINEAR DICHROISM

Differential diagnosis of intracerebral hemorrhage due to traumatic and non-traumatic origin is a challenging issue, especially in the absence of visible body injuries and other signs of violence. For a forensic expert-practitioner, the main thing is objectivity, accuracy, and speed of obtaining the result, which could fully satisfy the methods of laser polarimetry in the case of differential diagnosis of hemorrhages of traumatic and non-traumatic origin in the human brain matter.&#x0D; The purpose: To develop forensic criteria for the differential diagnosis of intracerebral hemorrhage of traumatic and non-traumatic origin using Mueller-matrix microscopy of linear dichroism.&#x0D; Materials and methods: The object of the study was brain matter samples, collected in 115 corpses of both sexes aged 22 to 86 years with accurately known causes of death. The causes of death included coronary artery disease, traumatic brain hemorrhage, ischemic brain infarction, and non-traumatic brain hemorrhages. Brain matter samples have been frozen rapidly, and histological sections have been made using a freezing microtome. The slices have been evaluated using the method of azimuthal-invariant Mueller-matrix microscopy, followed by mathematical and statistical processing of the results. &#x0D; Results: significant topographic heterogeneity of Mueller-matrix invariants of brain matter samples linear dichroism maps among all research groups have been found. Individual and significant variations of dispersion, asymmetry, and kurtosis magnitude have confirmed the heterogeneity of Mueller-matrix invariants. The difference of images and histograms among groups is explained by the presence of necrotic changes in the case of ischemic brain necrosis and blood cells in the brain matter samples. For the set of central statistical moments of the 1st, 3rd, and 4th orders, which characterize the distributions of circular dichroism, the method of MM-microscopy in the differentiation of samples of non-hemorrhage and hemorrhage groups reaches a satisfactory level - 78% - 84%.&#x0D; Conclusions: Brain matter samples Muller-matrix microscopy of linear dichroism is effective for solving diagnostic problems of forensic medicine related to evaluating the cause of death from intracerebral hemorrhage of various origins. Diagnostic efficiency of Mueller-matrix mapping of polarization manifestations of linear dichroism method for intergroup differentiation of samples of deaths from traumatic hemorrhage (Group 2) and ischemic cerebral infarction (Group 3) reaches a satisfactory level of 79 - 84%.

A follow-up study of patients with COVID-19 presenting with seizures

ObjectiveWe performed a follow-up study of patients with COVID-19 presenting with seizures. MethodsAll consecutive patients with seizures, who were referred to Namazee Hospital, Shiraz, Iran, with a diagnosis of COVID-19, from 10 August 2020 until 20 October 2020 were included in this longitudinal study. The clinical data were collected by the admitting physician. In a follow-up phone call to the discharged patients (after eight weeks or more), we inquired their seizure outcome. ResultsIn total, 32 patients were studied; 28 patients were followed. Twelve patients (37.5%) presented with a single tonic-clonic seizure and nine (28.1%) had convulsive status epilepticus; one patient had functional (psychogenic) seizures. Ten patients (31.3%) had pre-existing epilepsy, eight others (25%) had pre-existing CNS problems (without epilepsy), one person (3.1%) had pre-existing functional seizures, and 13 individuals (40.1%) neither had epilepsy nor had other CNS problems. Eight patients (28.6%) reported experiencing seizure(s) after being discharged from the hospital; six of these had pre-existing epilepsy and one had pre-existing functional seizures. One patient, who had a newly developed ischemic brain infarction, reported experiencing recurrent seizures. ConclusionSeizures in patients with COVID-19 are either acute symptomatic (in about two-thirds) or an exacerbation of a pre-existing epilepsy/functional seizures (in about one-third). A thorough investigation of the underlying etiology of seizures in patients with COVID-19 is necessary. Seizure outcome in patients, who are hospitalized with COVID-19 and seizures, is generally good.

ПЕРСПЕКТИВЫ ИСПОЛЬЗОВАНИЯ РАДИОНУКЛИДНЫХ МЕТОДОВ ИССЛЕДОВАНИЯ ДЛЯ ДИАГНОСТИКИ И ОЦЕНКИ ЭФФЕКТИВНОСТИ ЛЕЧЕНИЯ ПОСЛЕДСТВИЙ ПЕРЕНЕСЕННОЙ НОВОЙ КОРОНАВИРУСНОЙ ИНФЕКЦИИ

Purpose: to determine the role of nuclear medicine methods in the diagnosis and quality control of treatment and rehabilitation of patients with complications after coronavirus diseasr (COVID-19)&#x0D; The article provides a brief analysis of the incidence of COVID-19 and highlights the role of diagnosis, treatment and rehabilitation of patients suffering from the consequences of coronavirus diseasr after the end of the pandemic. The most common clinical manifestation of coronavirus diseasr is bilateral interstitial pneumonia, one of the complications of which is the development of acute respiratory distress syndrome, its pathogenesis is highlighted. It is also noted that the leading link in the development of the disease is a systemic lesion of the endothelial vascular wall, which is the cause of thrombosis and its complications, primarily pulmonary embolism, ischemic brain infarctions and cardiovascular catastrophes. &#x0D; Specific methods of radionuclide diagnostics are described for individual organs and systems: respiratory, cardiovascular, brain, and others. The need to diagnose and control the quality of treatment and rehabilitation of patients with post-inflammatory changes in the parenchyma of internal organs and a decrease in their functional ability due to sclerotic changes, patients with changes in the state due to the transition of inflammation to the chronic stage, as well as with an overactive immune response to inflammatory changes.&#x0D; Conclusion: at the stage of diagnosis and treatment of the consequences of a previous coronavirus diseasr and subsequent rehabilitation, molecular imaging methods are essential in a complex of studies.

Abstract P810: Dysregulation of Dipeptidyl Peptidase and Adipokines in Atherosclerosis and Ischemic Stroke

Introduction: Atherosclerosis and stroke remain the leading causes of death and functional disabilities. Stable carotid atherosclerosis (CA) plaques can rupture inducing ischemic stroke and functional impairment. However, there are gaps in our understanding of the molecular factors in cerebro-vascular diseases. Methods: Using pre-clinical animal models of atherosclerosis and ischemic stroke, we investigated the association of specific proteases and adipokines using cellular, molecular, proteomic, and biochemical approaches. We analyzed blood, brain, and aortic tissues obtained from wildtype, normal and high fat diet fed APO-E deficient mice with and without plaques, and . We examined the differential expression of levels of DPPIV and adipokines in plasma using a targeted proteome profiler antibody array. The levels of mRNA were assessed in APOE-/- aortic and brain tissues using pathway specific PCR arrays. Results: In a pre-clinical animal model of focal ischemic stroke, we found that DPPIV is significantly increased in the ischemic brain. Genetic ablation of DPPIV gene, decreased the ischemic brain infarct size in a middle cerebral artery occlusion induced ischemic mouse model. Furthermore, we observed upregulation of DPPIV expression in aortic root lesions and carotid arteries of atherogenic apolipoprotein E deficient (ApoE-/-) mice as compared to wild type animals. Circulating DPPIV levels in plasma were also significantly higher in ApoE-/- and stroke induced animals. In the plaque tissue, DPPIV was over-expressed in macrophages as indicated by its co-localization with Mac-2, and in endothelial cells (EC). Oxygen glucose deprivation induced in vitro ischemia also upregulated DPPIV expression in macrophages and EC. DPPIV decreased EC viability/mitochondrial potential, and disrupted endothelial function as shown by impaired pro-angiogenic structure formation. DPPIV expression was associated with increased levels of apoptotic and inflammatory adipokines/cytokines. Conclusion: DPPIV and adipokine dysregulation is associated with atherosclerosis and ischemic stroke. Imbalanced production of these factors may further worsen post-stroke outcome, and are potential targets for clinical intervention.

The Omega-3 Fatty Acid Eicosapentaenoic Acid (EPA) Correlates Inversely with Ischemic Brain Infarcts in Patients with Atrial Fibrillation.

The omega-3 fatty acid (n-3 FA) eicosapentaenoic acid (EPA) reduces stroke in patients with atherosclerotic cardiovascular disease. Whether EPA affects stroke or cerebral small vessel dis-ease in patients with atrial fibrillation (AF) remains uncertain. EPA, docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and alpha-linolenic acid (ALA) were determined by gas chromatography in 1657 AF patients from the Swiss Atrial Fibrillation study. All patients underwent brain MRI to detect ischemic brain infarcts, classified as large noncortical or cortical infarcts (LNCCIs); markers of small vessel disease, classified as small noncortical infarcts (SNCIs), number of microbleeds, and white matter lesion (WML) volumes. Individual and total n-3 FAs (EPA + DHA + DPA + ALA) were correlated with LNCCIs and SNCIs using logistic regression, with numbers of microbleeds using a hurdle model, and WML volumes using linear regression. LNCCIs were detected in 372 patients (22.5%). EPA correlated inversely with the prevalence of LNCCIs (odds ratio [OR] 0.51 per increase of 1 percentage point EPA, 95% confidence interval [CI] 0.29–0.90). DPA correlated with a higher LNCCI prevalence (OR 2.48, 95%CI 1.49–4.13). No associations with LNCCIs were found for DHA, ALA, and total n-3 FAs. Neither individual nor total n-3 FAs correlated with markers of small vessel disease. In conclusion, EPA correlates inversely with the prevalence of ischemic brain infarcts, but not with markers of small vessel disease in patients with AF.

MicroRNA-488-3p Regulates Neuronal Cell Death in Cerebral Ischemic Stroke Through Vacuolar Protein Sorting 4B (VPS4B).

BackgroundIschemic stroke, which often occurs with high morbidity, disability, and mortality, is a main cause of brain disease. In various types of human diseases, it is found that microRNAs (miRNAs) are considered as gene regulators. Increasing studies have proved that fluctuation of miRNAs, in the pathologies of ischemic stroke, plays a vital role. However, the accurate regulatory mechanism of cerebral ischemic stroke by miRNAs is still unclear. In this research, we investigated the inhibition mechanism of miR-488-3p on neuronal death through targeting vacuolar protein sorting 4B (VPS4B) in cerebral ischemia/reperfusion (I/R) injury.MethodsWestern blot and qRT-PCR were utilized to detect the miR-488-3p level and VPS4B expression. The cell counting kit-8 (CCK-8) assay was utilized to measure the function of miR-488-3p in cell death induced by oxygen glucose deprivation/reoxygenation (OGD/R). After middle cerebral artery occlusion/reperfusion (MCAO/R), the impact of miR-488-3p on infarct volume in mouse brain was assessed. The targets of miR-488-3p were confirmed by luciferase analysis and bioinformatics software.ResultsThe miR-488-3p level remarkably reduced in primary neuronal cells administrated with OGD/R. Similarly, it also decreased in the mouse brain administrated with MCAO/R. Additionally, the up-regulation of miR-488-3p expression suppressed the death of neuronal cells and restrained ischemic brain infarction in ischemia-stroked mice. Besides, the results showed that VPS4B, which could be inhibited by miR-488-3p, was a direct target of miR-488-3p. This research revealed that the inhibition of VPS4B protected the neuronal cells in ischemic stroke both in vitro as well as in vivo. Meanwhile, this inhibition strengthened positive impact generated by miR-488-3p on ischemic injury.ConclusionOverall, miR-488-3p played a critical role on neuroprotective function via reducing VPS4B protein level. These results performed a new underlying curative target for the treatment of cerebral ischemic stroke.

A Study on First Ischemic Stroke Patients for Prevalence of Extracranial Carotid Artery Stenosis and Risk Factors: Our Experience in Northeast India and Review of Literature

Objective: To assess the prevalence of carotid artery stenosis and risk factors in stroke patients of northeast India. This is a prospective hospital-based study on 157 first ischemic stroke patients of the region. Method: A total of 157 patients presenting with first ever sudden onset focal neurological deficit lasting for more than 24 hours due to acute ischemic brain infarction were selected, after excluding other causes of focal neurological deficit by imaging. All extracranial carotid arteries were evaluated with carotid ultrasonography. Forty-four patients also had computed tomography (CT) angiography of intracranial and extracranial arteries. Risk factors of stroke were recorded for each patient. Results: Only 8.92% patients had significant extracranial carotid artery stenosis. There was high prevalence of intracranial artery stenosis compared to extracranial artery stenosis in patients who had CT angiography. There was high prevalence of hypertension, dyslipidemia, and diabetes. Increased age and male sex were important factors associated with first ischemic stroke. Conclusion: The prevalence of significant extracranial carotid artery stenosis is low in northeast Indian patients with first ischemic stroke, indicating that it is not a major cause of ischemic stroke in this population. There may be high prevalence of intracranial artery stenosis compared to extracranial artery stenosis.