Acute Cerebrovascular Disease Research Articles

Astragaloside IV alleviates stroke-triggered early brain injury by modulating neuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway.

Stroke is an acute cerebrovascular disease. Astragaloside IV (AS-IV) is an active ingredient extracted from Astragalus membranaceus with an established therapeutic effect on central nervous system diseases. This study examined the neuroprotective properties and possible mechanisms of AS-IV in stroke-triggered early brain injury (EBI) in a rat transient middle cerebral artery occlusion (MCAO) model. The neurological scores and brain water content were analyzed. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was utilized to determine the infarct volume, neuroinflammatory cytokine levels, and ferroptosis-related genes and proteins, and neuronal damage and molecular mechanisms were evaluated by terminal deoxynucleotidyl transferase dutp nick-end labeling (TUNEL) staining, western blotting, and real-time polymerase chain reaction. AS-IV administration decreased the infarct volume, brain edema, neurological deficits, and inflammatory cytokines TNF-α, interleukin-1β (IL-1β), IL-6, and NF-κB, increased the levels of SLC7A11 and glutathione peroxidase 4 (GPX4), decreased lipid reactive oxygen species (ROS) levels, and prevented neuronal ferroptosis. Meanwhile, AS-IV triggered the Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of stroke. Hence, the findings of this research illustrate that AS-IV administration can improve delayed ischemic neurological deficits and decrease neuronal death by modulating nuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway.

Retracted: A Study of the Relationship between Blood Glucose and Serum Insulin in Acute Cerebrovascular Disease.

[This retracts the article DOI: 10.1155/2022/9041551.].

Analysis of the Effects of Betahistine Hydrochloride Combined with Atorvastatin on Procalcitonin and C-Reactive Protein Levels in Acute Cerebrovascular Disease

Analysis of the Effects of Betahistine Hydrochloride Combined with Atorvastatin on Procalcitonin and C-Reactive Protein Levels in Acute Cerebrovascular Disease

The Effect of PGAM5 on Regulating Mitochondrial Dysfunction in Ischemic Stroke.

Ischemic stroke is an acute cerebrovascular disease with high mortality rates and poor prognoses. The influence of ischemic stroke includes a heavy economic burden to patients and society, making the exploration of new therapeutic targets for preventing and treating ischemic stroke urgent. This study aimed to explore the effect of phosphoglycerate mutase family member 5 (PGAM5) on oxidative stress and mitochondrial dysfunction in ischemic stroke. The model of ischemic neuronal brain injury was established through culturing purchased human neuroblastoma cells (SH-SY5Y) by oxygen-glucose deprivation/reoxygenation (OGD/R). There were six experimental groups, including the OGD/R model group (SH-cells of OGD/R model), OE-NC group (cells of OGD/R model transfected with scramble cDNA), OE-PGAM5 group (cells of OGD/R model transfected with full-length sequence of PGAM5), si-NC group (cells of OGD/R model transfected with negative control small interference (si)RNA), si-PGAM5 group (cells of OGD/R model transfected with siRNA for PGAM5 knockdown), and a control group (cells cultured normally). Cell counting kit-8 (CCK-8) and flow cytometry were used to determine the activity and apoptosis of cells. Subsequently, the effects of PGAM5 expression on oxidative stress and mitochondrial dysfunction were analyzed. Mitochondrial morphology was observed by transmission electron microscopy (TEM), and mitochondrial membrane potential (MMP) was determined by JC-1 fluorescent probe. The levels of reactive oxygen species (ROS) were measured by flow cytometry, and levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured by enzyme-linked immunosorbent assay (ELISA) assay. The expression of light chain (LC)3-II/I and autophagy-related gene 5 (ATG5) proteins were measured, and the regulation of PGAM5 expression on PTEN-induced putative protein kinase 1 (PINK1)/Parkin pathway was also explored. PGAM5 overexpression in OGD/R cells decreased the cell viability (p < 0.001) while increasing cell apoptosis (p < 0.01) compared to the OGD/R group. Inhibition of PGAM5 expression reversed the decreased cell viability (p < 0.001) and the increased cell apoptosis (p < 0.01). The JC-1 fluorescence showed that OGD/R treatment reduced mitochondrial membrane potential (p < 0.001) and TEM showed an obvious increase in phagosomes. In addition, OGD/R treatment enhanced oxidative stress (increased ROS, p < 0.01; increased MDA, p < 0.001; decreased SOD, p < 0.001), which could be further enhanced by overexpression of PGAM5 (ROS, p < 0.001; MDA, p < 0.001; SOD, p < 0.001) while reversed by the inhibition of PGAM5 (ROS, p < 0.01; MDA, p < 0.001; SOD, p < 0.001). The OGD/R-activated PINK1/Parkin pathway was inhibited by the knockdown of PGAM5 (p < 0.01) but promoted by the overexpression of PGAM5 (p < 0.05). PGAM5 stimulates oxidative stress and impairs mitochondrial function in ischemic stroke, and regulates the PINK1/Parkin signaling pathway. Therefore, PGAM5 is likely to be a target for the therapy of ischemic stroke.

Long-Term Prognosis of Patients with Heart Failure: Follow-Up Results of Journey HF-TR Study Population.

Despite advances in therapeutic management of patients with heart failure, there is still an increasing morbidity and mortality all over the world. In this study, we aimed to present the 3-year follow-up outcomes of patients included in the Journey HF-TR study in 2016 that has evaluated the clinical characteristics and management of patients with acute heart failure admitted to the hospital and present a national registry data. The study was designed retrospectively between November 2016 and December 2019. Patient data included in the previously published Journey HF-TR study were used. Among 1606 patients, 1484 patients were included due to dropout of 122 patients due to inhospital death and due to exclusion of 173 due to incomplete data. The study included 1311 patients. Age, gender, concomitant chronic conditions, precipitating factors, New York Heart Association, and left ventricular ejection fraction factors were adjusted in the Cox regression analysis. During the 3-year follow-up period, the ratio of hospitalization and mortality was 70.5% and 52.1%, respectively. Common causes of mortality were acute decompensation of heart failure and acute coronary syndrome. Angiotensin receptor blockers, betablockers, statin, and sacubitril/valsartan were found to reduce mortality. Hospitalization due to acute decompensated heart failure, acute coronary syndrome, lung diseases, oncological diseases, and cerebrovascular diseases was associated with the increased risk of mortality. Implantation of cardiac devices also reduced the mortality. Despite advances in therapeutic management of patients with heart failure, our study demonstrated that the long-term mortality still is high. Much more efforts are needed to improve the inhospital and long-term survival of patients with chronic heart failure.

Dexmedetomidine promotes the functional recovery of mice after acute ischemic stroke via activation of the a2-adrenoceptor.

Ischemic stroke (IS) is a well-known acute cerebrovascular disease characterized by high disability, morbidity, and recurrence rates with no effective treatments. Dexmedetomidine (DEX), a selective a2-adrenoceptor agonist used in anaesthesiology and pain management, has been found to exhibit neuroprotective effects in various diseases. However, its role in IS and the underlying mechanisms remains to be determined. Hence, the aim of the present study was to investigate the neuroprotective role of DEX in the recovery of mice following middle cerebral artery occlusion (MCAO). Mice were used to establish the animal model, and then DEX was injected. Behavioural tests (neurological function assessments, grip test, and rotarod test), brain water content measurement, ELISA, and measurement of oxidative stress were performed. DEX activated a2-adrenoceptor and resulted in reduced brain injury, as indicated by the decreased brain water content, S100 Calcium Binding Protein B (S100B) content, and neuron-specific enolase (NSE) content, whilst also inhibiting oxidative stress, as indicated by the increased total antioxidant capacity, catalase, glutathione, and superoxide dismutase levels, and decreased malondialdehyde and glutathione oxidized levels. Neuroinflammation was also reduced as indicated by the decrease in IFN-g, IL-1a, IL-1b, IL-6, TNF-a, and MMP levels, improved the recovery of neurological function, as indicated by the decreased neurological function score and mNSS, and increased grip strength and rotarod performance in MCAO mice. These combined results suggest that DEX may be a novel strategy for the treatment of IS.

Transmembrane p24 trafficking protein 10 (TMED10) inhibits mitochondrial damage and protects neurons in ischemic stroke via the c-Jun N-terminal kinase (JNK) signaling pathway.

Stroke, a type of acute cerebrovascular disease, is a global disease with high mortality. Neuronal ischemia and hypoxia are closely related to occurrence and development of cognitive impairment. Transmembrane p24 trafficking protein 10 (TMED10) as a transmembrane protein involves in vesicle protein transport in the secretory pathways. However, the function and mechanism of TMED10 on ischemic stroke and cognitive impairments remain unclear. In current study, TMED10 was highly expressed in cerebral ischemic penumbra of middle cerebral artery occlusion (MCAO) mouse model. Downregulation of TMED10 suppressed cell survival and facilitated apoptosis in primary cortical neurons, which were grown under oxygen glucose deprivation/reoxygenation (OGD/R) condition. Upregulation of TMED10 protected neurons form apoptosis induced by OGD/R. Further research indicated that the decrease of TMED10 resulted in neuronal mitochondrial injury through increasing reactive oxygen species (ROS) production. Meanwhile, TMED10 reduction induced neuronal apoptosis and mitochondrial damage through activating the c-Jun N-terminal kinase (JNK) pathway. Moreover, the knockdown of TMED10 increased cerebral infarction area, aggravated neuronal injury and promoted neuronal apoptosis through activating the JNK pathway in the cerebral ischemic penumbra of MCAO mouse model. Additionally, Morris water maze test verified that the severity of cognitive impairment increased with the decline of TMED10. Collectively, this study reveals that TMED10 inhibits mitochondrial damage, and protects neurons from apoptosis in MCAO-induced ischemic stroke and cognitive impairment via blocking the JNK pathway.

Retracted: Combined Application of CT Perfusion Imaging and CT Angiography in Imaging Diagnosis of Acute Cerebrovascular Diseases.

[This retracts the article DOI: 10.1155/2021/4825285.].

Transcranial Doppler analysis based on computer and artificial intelligence for acute cerebrovascular disease

Cerebrovascular disease refers to damage to brain tissue caused by impaired intracranial blood circulation. It usually presents clinically as an acute nonfatal event and is characterized by high morbidity, disability, and mortality. Transcranial Doppler (TCD) ultrasonography is a non-invasive method for the diagnosis of cerebrovascular disease that uses the Doppler effect to detect the hemodynamic and physiological parameters of the major intracranial basilar arteries. It can provide important hemodynamic information that cannot be measured by other diagnostic imaging techniques for cerebrovascular disease. And the result parameters of TCD ultrasonography such as blood flow velocity and beat index can reflect the type of cerebrovascular disease and serve as a basis to assist physicians in the treatment of cerebrovascular diseases. Artificial intelligence (AI) is a branch of computer science which is used in a wide range of applications in agriculture, communications, medicine, finance, and other fields. In recent years, there are much research devoted to the application of AI to TCD. The review and summary of related technologies is an important work to promote the development of this field, which can provide an intuitive technical summary for future researchers. In this paper, we first review the development, principles, and applications of TCD ultrasonography and other related knowledge, and briefly introduce the development of AI in the field of medicine and emergency medicine. Finally, we summarize in detail the applications and advantages of AI technology in TCD ultrasonography including the establishment of an examination system combining brain computer interface (BCI) and TCD ultrasonography, the classification and noise cancellation of TCD ultrasonography signals using AI algorithms, and the use of intelligent robots to assist physicians in TCD ultrasonography and discuss the prospects for the development of AI in TCD ultrasonography.

Significant Mortality Associated With COVID-19 and Comorbid Cerebrovascular Disease: A Quantitative Systematic Review.

We report the first quantitative systematic review of cerebrovascular disease in coronavirus disease 2019 (COVID-19) to provide occurrence rates and associated mortality. Through a comprehensive search of PubMed we identified 8 cohort studies, 5 case series, and 2 case reports of acute cerebrovascular disease in patients with confirmed COVID-19 diagnosis. Our first meta-analysis utilizing the identified publications focused on comorbid cerebrovascular disease in recovered and deceased patients with COVID-19. We performed 3 additional meta-analyses of proportions to produce point estimates of the mortality and incidence of acute cerebrovascular disease in COVID-19 patients. Patient's with COVID-19 who died were 12.6 times more likely to have a history of cerebrovascular disease. We estimated an occurrence rate of 2.6% (95% confidence interval, 1.2-5.4%) for acute cerebrovascular disease among consecutively admitted patients with COVID-19. While for those with severe COVID-19' we estimated an occurrence rate of 6.5% (95% confidence interval, 4.4-9.6%). Our analysis estimated a rate of 35.5% for in-hospital mortality among COVID-19 patients with concomitant acute cerebrovascular disease. This was consistent with a mortality rate of 34.0% which we obtained through an individual patient analysis of 47 patients derived from all available case reports and case series. COVID-19 patients with either acute or chronic cerebrovascular disease have a high mortality rate with higher occurrence of cerebrovascular disease in patients with severe COVID-19.

Sneddon syndrome: A rare diagnosis

The study objective is to demonstrate a rare cause of recurrent acute cerebrovascular diseases in a young patient – Sneddon syndrome. The patient revealed gene polymorphism: homozygous 4G/5G in the plasminogen activator inhibitor-1 (PAI-1) gene, C807T in the glycoprotein I gene (GPIa), T1565C in the glycoprotein III gene (GPIIIa), G1639A in the vitamin K epoxide reductase gene (VKORC1), increased homocysteine, which were risk factors for thrombosis.

Risk factors and predictors of acute gastrointestinal injury in stroke patients

PurposeThis prospective study investigates the incidence, risk factors, biological markers, and predictors of acute gastrointestinal injury (AGI) in patients with stroke. MethodsThe study involved a total of 98 patients with acute cerebrovascular disease were included. According to the ESICM, the definition of AGI in intensive care patients is classified as grade 0, I, II and III. Patients’ demographics, serological indicators (e.g., urea nitrogen, albumin, D-lactate, α-GST, neutrophil count and lymphocyte count), relevant scores (NIHSS score, GCS score, APACHE II score), length of hospital stay as well as the 7-day and 28-day mortality were recorded. ResultsIn 98 patients, the incidence of AGI was 90.8 %. The APACHE II, NIHSS, GCS and Hs-mGPS scores significantly increased the odds of a higher AGI grade (P < 0.05). Also, current use of antibiotics and the presence of pneumonia significantly increased the probability of a higher AGI grade (P < 0.05). NLR, diabetes and dehydrating drugs increased the probability of AGI grade II and III (P < 0.05). Finally, an early commencement of endovascular treatment significantly reduced the incidence of AGI class III (P < 0.05). Patients with higher AGI grades had longer hospital stays and higher 28-day mortality (P < 0.05). ConclusionThe degree of the neurological deficit in stroke patients (high NIHSS score, low GCS score) in this study was associated with the development of AGI. The patients' gastrointestinal barrier function continued to deteriorate during the week of onset. The APACHE II score, NRL score and HS-mGPS score have some predictive value for the occurrence of AGI in stroke patients.

Neurological Manifestations of hospitalized patients with mild to moderate infection with SARS-CoV-2 Omicron variant in Shanghai, China

BackgroundAccumulating studies demonstrated that patients with coronavirus disease 2019(COVID-19) could develop a variety of neurological manifestations and long-term neurological sequelae, which may be different from the strains. At the peak of the Omicron variant outbreak in Shanghai, China, no relevant epidemiological data about neurological manifestations associated with this strain was reported. ObjectiveTo investigate neurological manifestations and related clinical features in patients with mild to moderate COVID-19 patients with Omicron variant. MethodsA self-designed clinical information registration form was used to gather the neurological manifestations of mild to moderate COVID-19 patients admitted to a designated hospital in Shanghai from April 18, 2022 to June 1, 2022. Demographics, clinical presentations, laboratory findings, treatments and clinical outcomes were compared between patients with and without neurological manifestations. ResultsOne hundred sixty-nine(48.1 %) of 351 patients diagnosed with mild to moderate COVID-19 exhibited neurological manifestations, the most common of which were fatigue/weakness(25.1 %) and myalgia(20.7 %), whereas acute cerebrovascular disease(0.9 %), impaired consciousness(0.6 %) and seizure(0.6 %) were rare. Younger age(p = 0.001), female gender(p = 0.026) and without anticoagulant medication(p = 0.042) were associated with increasing proportions of neurological manifestations as revealed by multivariate logistic regressions. Patients with neurological manifestations had lower creatine kinase and myoglobin levels, as well as higher proportion of patchy shadowing on chest scan. Vaccination status, clinical classification of COVID-19 and clinical outcomes were similar between the two groups. ConclusionsNearly half of the involved patients have neurological manifestations which were relatively subjective and closely associated with younger age, female gender and without anticoagulation. Patients with neurologic manifestations may be accompanied by increased lung patchy shadowing.

Prevalence of neurological complaints among emergency department patients with severe hypertension

ObjectiveSevere hypertension can accompany neurological symptoms without obvious signs of target organ damage. However, acute cerebrovascular events can also be a cause and consequence of severe hypertension. We therefore use US population-level data to determine prevalence and clinical characteristics of patients with severe hypertension and neurological complaints. MethodsWe used nationally representative data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) collected in 2016–2019 to identify adult ED patients with severely elevated blood pressure (BP) defined as systolic BP ≥ 180 mmHg and/or diastolic BP ≥120 mmHg. We used ED reason for visit data fields to define neurological complaints and used diagnosis data fields to define acute target organ damage. We applied survey visit weights to obtain national estimates. ResultsBased on 5083 observations, an estimated 40.4 million patients (95% CI: 37.5–43.0 million) in EDs nationwide from 2016 to 2019 had severe hypertension, equating to 6.1% (95% CI: 5.7–6.5%) of all ED visits. Only 2.8% (95% CI: 2.0–3.9%) of ED patients with severe hypertension were diagnosed with acute cerebrovascular disease; hypertensive urgency was diagnosed in 92.0% (95% CI: 90.3–93.4%). Neurological complaints were frequent in both patients with (75.6%) and without (19.9%) cerebrovascular diagnoses. Hypertensive urgency patients with neurological complaints were more often older, female, had prior stroke/TIA, and had neuroimaging than patients without these complaints. Non-migraine headache and vertigo were the most common neurological complaints recorded. ConclusionIn a nationally representative survey, one-in-sixteen ED patients had severely elevated BP and one-fifth of those patients had neurological complaints.

Advances in the therapy of cerebral ischemia-reperfusion injury with natural product-based nanoparticles

Stroke is a serious acute cerebrovascular disease attributable to disruptions in the blood supply to the brain tissue as a result of vascular obstruction or sudden rupture of blood vessels in the brain, which further result in hypoxia of the brain and reduction of necessary nutrients, apoptosis of neurons, and damage to brain tissue. The majority of stroke patients are ischemic stroke. The main clinical treatments for ischemic stroke include medical thrombolysis in the early stage of onset and surgical thrombectomy or stent implantation in the late stage of onset, all of which have their own indications, advantages, and disadvantages, and show limited clinical application. For cerebral ischemia-reperfusion injury with an extremely poor prognosis, there is currently no effective prevention and treatment method in the clinic. Therefore, timely and effective treatment is needed to treat cerebral ischemia-reperfusion injury. An increasing number of studies have shown that natural products have a good curative effect on cerebral ischemia-reperfusion injury. However, due to their low solubility, low bioavailability, and short half-life, many natural products cannot optimally exert their curative effects on cerebral ischemia-reperfusion injury. Natural products-based nanoparticles modified with specific ligands have attracted much attention because of their high-efficiency permeation through the blood–brain barrier, targeted delivery abilities, and the protection of the active components from degradation. Therefore, this review focused on the prevention and treatment of cerebral ischemia-reperfusion injury in the natural product-based nanoparticles.

Neurological Manifestations of Hospitalized COVID-19-Infected Patients: A Single-Center Cohort Study

Background: Although COVID-19 preferentially affects the respiratory system, it has been demonstrated that coronaviruses frequently invade the nervous system. Objectives: We aimed to report the frequency and type of neurological manifestations in hospitalized patients with COVID-19. Methods: This is a retrospective, prospective observational cohort study. Data were collected from April to July 2020 at Bu-Ali Sina University Hospital, Sari, Iran. Demographic data and clinical symptoms were recorded at the onset of the disease. Neurological manifestations were recorded into 5 categories: nonspecific central nervous system (CNS) manifestations, acute cerebrovascular disease (CVD), meningitis/encephalitis, peripheral nervous system manifestations, and inflammatory disorders (myelitis and acute disseminated encephalomyelitis). Results: A total of 420 patients were admitted to the hospital with confirmed SARS-CoV-2 infection. Of the 420 patients hospitalized with COVID-19, 282 (67%) showed some form of neurological symptoms, of whom 48.33% had nonspecific neurological symptoms. Further, 35 (8.3%) patients had acute CVD, 2 patients had encephalitis (the RNA of SARS-CoV-2 was detected in cerebrospinal fluid (CSF), 1 patient had myelitis, and 83 (19.76%) patients had peripheral nervous system manifestations. Conclusions: Neurologic symptoms (from mild symptoms to life-threatening CNS disorders) are common in admitted patients with COVID-19. As a result of coagulation disorder in patients with COVID-19, some conditions (such as stroke) can be seen, even during recovery.

A New Therapeutic Trend: Natural Medicine for Ameliorating Ischemic Stroke via PI3K/Akt Signaling Pathway.

Ischemic stroke (IS) is an acute cerebrovascular disease caused by sudden arterial occlusion, which is characterized by a high morbidity, mortality, and disability rate. It is one of the most important causes of nervous system morbidity and mortality in the world. In recent years, the search for new medicine for the treatment of IS has become an attractive research focus. Due to the extremely limited time window of traditional medicine treatment, some side effects may occur, and accompanied by the occurrence of adverse reactions, the frequency of exploration with natural medicine is significantly increased. Phosphatidylinositol-3-kinase/Protein kinase B (PI3K/Akt) signaling pathway is a classical pathway for cell metabolism, growth, apoptosis, and other physiological activities. There is considerable research on medicine that treats various diseases through this pathway. This review focuses on how natural medicines (including herbs and insects) regulate important pathophysiological processes such as inflammation, oxidative stress, apoptosis, and autophagy through the PI3K/Akt signaling pathway, and the role it plays in improving IS. We found that many kinds of herbal medicine and insect medicine can alleviate the damage caused by IS through the PI3K/Akt signaling pathway. Moreover, the prescription after their combination can also achieve certain results. Therefore, this review provides a new candidate category for medicine development in the treatment of IS.

Didang Tang inhibits intracerebral hemorrhage-induced neuronal injury via ASK1/MKK7/JNK signaling pathway, network pharmacology-based analyses combined with experimental validation

BackgroundIntracerebral hemorrhage (ICH) is an acute cerebrovascular disease, which is also a principal consideration for disability. Didang tang (DDT) is a classic traditional Chinese medicine formula for treating ICH. However, its pharmacological mechanism of action has not been elucidated. Materials and methodsThe TCMSP and BATMAN-TCM databases were used to collect chemical compounds and predict targets of DDT. Protein targets in ICH were identified by GeneCards, OMIM, and DrugBank databases. DDT compounds-ICH targets and protein-protein interaction (PPI) networks were constructed for topological analysis and hub-targets screening. Further, Key biological processes and signaling pathways were identified by GO and KEGG enrichment analyses. Then, an ICH rat model and a Cobaltous Chloride (CoCl2)-induced PC12 cells model were established. Cell viability and lactate dehydrogenase (LDH) release were detected using cck8 and LDH kits. Apoptosis levels were detected by TUNEL assessment and flow cytometry. IL-1β levels were detected by ELISA, while key protein expressions were determined by Western blot. ResultsA total of 126 active compounds related to DDT and 3,263 therapeutic targets for ICH were predicted. The functional enrichment of the GO and KEGG pathways combined with literature studies suggested that DDT is most likely to influence MAPK and apoptotic signaling pathways for ICH treatment. In vitro and in vivo experiments have shown that DDT remarkably inhibited apoptosis and increased the expression of Bcl-2, while inhibiting Bax and cleaved-Caspase 3. For other enriched core proteins, DDT suppressed the phosphorylation of Src and the expression of c-Myc and IL-1β, and up-regulated the level of MMP-9. The further results showed that, DDT decreased the phosphorylation of ASK1, MKK7, JNK and c-JUN. ConclusionBased on network pharmacology and experimental validation results, our in vivo and in vitro study indicated that ASK1/MKK7/JNK pathway might be the critical target for DDT against ICH.

Neurologic symptoms and signs observed in critical COVID-19 patients may be precursors of existing cerebrovascular disease

Introduction: Although COVID-19 disease often includes respiratory system findings, that affects the gastrointestinal system, circulatory system, coagulation system and neurological system. In this study, we identified the neurological signs and symptoms observed in critical COVID-19 patients.&#x0D; Material and Method: This retrospective study reviewed 595 COVID-19 patients admitted to our intensive care unit (ICU) between January to June 2020. Patients with neurologic symptoms that were divided into two groups were diagnosed neurological disease (group ND) and non-neurological disease (group non-ND). Clinical signs and symptoms, radiological findings, demographic data (age, gender, presence of comorbidities), white blood cell (WBC), lymphocyte, platelet, lactic acid, glucose, and D-dimer levels, length of hospitalization, requirement of mechanical ventilation, and mortality were recorded for each patient.&#x0D; Results: Neurologic symptoms were observed in 148 (24.8%) patients. Of these, 44 patients were diagnosed neurological disease and 104 patients were non- neurological disease. The prevalence of neurologic symptoms was significantly higher in group ND. The rate of acute ischemic cerebrovascular disease in 595 critical COVID-19 patients was 6.2%.&#x0D; Conclusion: Presence of cerebrovascular diseases should be suspected in COVID-19patients with paresis, altered consciousness, numbness, taste/smell disorders, and plegia. The rate of ischemic cerebrovascular disease was approximately seven times higher than the rate of hemorrhagic cerebrovascular disease in critically COVID-19 patients.

Screening potential anaphylactoid components in vinpocetine injection using a high expression Mas-related G-protein-coupled receptor X2 cell membrane chromatography.

Vinpocetine injection is often used in clinical treatment of acute cardiovascular and cerebrovascular diseases. However, it was reported that vinpocetine injection caused allergic reactions in clinical use; therefore, its safety needs urgent attention. Until now, research on its sensitization is rarely reported. Here, the components contained in three vinpocetine injections were examined. It was found that besides vinpocetine, the synthetic raw material vincamine, the excipients benzyl alcohol and ethyl p-toluenesulfonate, and the impurities A, B, C, and D, which are excipients specified in the European Pharmacopoeia, were also present in them. Then the Mas-related G-protein-coupled receptor X2 (MRGPRX2)-HEK293 cell membrane chromatography was used to investigate the affinity of them with MRGPRX2 and found that vinpocetine, vincamine, and impurities A, B, C, and D bind to MRGPRX2. Afterwards, these compounds were further used to investigate the local sensitization ability in vivo. The results showed that vinpocetine, vincamine, and impurity C could induce swelling of the paw and decrease body temperature in mice, but only impurity C could cause local skin mast cell degranulation and serum histamine release increase. In vitro, the results also indicated that impurity C could increase intracellular [Ca2+ ] in MRGPRX2-HEK293 cells, whereas vinpocetine and vincamine did not. Therefore, the impurity C was the potential anaphylactoid component in vinpocetine injection, which may be one of the reasons for the occurrence of allergic reactions in the clinical use of vinpocetine injection. This work provides evidence on the sensitization of impurity C and also contributes to promoting the clinical safety of vinpocetine injection.