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2.
Molecules ; 26(20)2021 Oct 11.
Article in English | MEDLINE | ID: covidwho-1480881

ABSTRACT

We performed an in silico, in vitro, and in vivo assessment of a potassium 2-[2-(2-oxo-4-phenylpyrrolidin-1-yl) acetamido]ethanesulfonate (compound 1) as a potential prodrug for cognitive function improvement in ischemic brain injury. Using in silico methods, we predicted the pharmacological efficacy and possible safety in rat models. In addition, in silico data showed neuroprotective features of compound 1, which were further supported by in vitro experiments in a glutamate excitotoxicity-induced model in newborn rat cortical neuron cultures. Next, we checked whether compound 1 is capable of crossing the blood-brain barrier in intact and ischemic animals. Compound 1 improved animal behavior both in intact and ischemic rats and, even though the concentration in intact brains was low, we still observed a significant anxiety reduction and activity escalation. We used molecular docking and molecular dynamics to support our hypothesis that compound 1 could affect the AMPA receptor function. In a rat model of acute focal cerebral ischemia, we studied the effects of compound 1 on the behavior and neurological deficit. An in vivo experiment demonstrated that compound 1 significantly reduced the neurological deficit and improved neurological symptom regression, exploratory behavior, and anxiety. Thus, here, for the first time, we show that compound 1 can be considered as an agent for restoring cognitive functions.


Subject(s)
Ischemic Stroke/drug therapy , Pyrrolidines/chemistry , Pyrrolidines/pharmacology , Animals , Behavior, Animal/drug effects , Brain Ischemia , Cognition/drug effects , Cognition/physiology , Disease Models, Animal , Glutamic Acid/pharmacology , Infarction, Middle Cerebral Artery , Ischemic Stroke/physiopathology , Male , Molecular Docking Simulation , Neurons/drug effects , Neuroprotective Agents/pharmacology , Primary Cell Culture , Pyrrolidines/chemical synthesis , Rats , Rats, Wistar , Stroke
4.
J Stroke Cerebrovasc Dis ; 30(12): 106121, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1415617

ABSTRACT

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.


Subject(s)
COVID-19/complications , Fibrinolytic Agents/administration & dosage , Ischemic Stroke/drug therapy , Thrombolytic Therapy , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , Disability Evaluation , Europe , Female , Fibrinolytic Agents/adverse effects , Hospital Mortality , Humans , Infusions, Intravenous , Intracranial Hemorrhages/chemically induced , Iran , Ischemic Stroke/complications , Ischemic Stroke/diagnosis , Ischemic Stroke/mortality , Male , Middle Aged , Risk Assessment , Risk Factors , Thrombolytic Therapy/adverse effects , Thrombolytic Therapy/mortality , Time Factors , Treatment Outcome
6.
J Stroke Cerebrovasc Dis ; 30(9): 105944, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1267765

ABSTRACT

Ten days after SARS-Cov2 reinfection with mild gastrointestinal symptoms and headache that occurred 2 months after an initial infection, a previously healthy 37-year-old woman developed fluctuating facial and upper limb paresthesia and weakness. Diffusion-weighted magnetic resonance imaging revealed ischemic lesions in the right parietal region of different stages within the same vascular territory. A cerebral angiography demonstrated an isolated focal arteriopathy with no other arterial involvement. Focal cerebral arteriopathy is exceedingly rare among adults and most commonly triggered by varicella-zoster virus reactivation. We present a case of focal cerebral arteriopathy in a patient with a recent reinfection with SARS-CoV-2.


Subject(s)
COVID-19/complications , Cerebral Arterial Diseases/etiology , Ischemic Stroke/etiology , Reinfection , Adult , COVID-19/diagnosis , COVID-19/virology , Cerebral Angiography , Cerebral Arterial Diseases/diagnostic imaging , Cerebral Arterial Diseases/drug therapy , Diffusion Magnetic Resonance Imaging , Dual Anti-Platelet Therapy , Female , Humans , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/drug therapy , Magnetic Resonance Angiography , Platelet Aggregation Inhibitors/administration & dosage , Tomography, X-Ray Computed , Treatment Outcome
9.
Int J Mol Med ; 47(3)2021 03.
Article in English | MEDLINE | ID: covidwho-1067806

ABSTRACT

During the coronavirus disease 2019 (COVID­19) pandemic, some patients with severe COVID­19 exhibited complications such as acute ischemic stroke (AIS), which was closely associated with a poor prognosis. These patients often had an abnormal coagulation, namely, elevated levels of D­dimer and fibrinogen, and a low platelet count. Certain studies have suggested that COVID­19 induces AIS by promoting hypercoagulability. Nevertheless, the exact mechanisms through which COVID­19 leads to a hypercoagulable state in infected patients remain unclear. Understanding the underlying mechanisms of hypercoagulability is of utmost importance for the effective treatment of these patients. The present review aims to summarize the current status of research on COVID­19, hypercoagulability and ischemic stroke. The present review also aimed to shed light into the underlying mechanisms through which COVID­19 induces hypercoagulability, and to provide therapies for different mechanisms for the more effective treatment of patients with COVID­19 with ischemic stroke and prevent AIS during the COVID­19 pandemic.


Subject(s)
COVID-19/physiopathology , Ischemic Stroke/etiology , Thrombophilia/etiology , COVID-19/complications , Humans , Ischemic Stroke/drug therapy , Ischemic Stroke/prevention & control
10.
BMC Neurol ; 21(1): 4, 2021 Jan 05.
Article in English | MEDLINE | ID: covidwho-1007170

ABSTRACT

BACKGROUND: The COVID-19 pandemic, which broke out in Wuhan in 2019, has become the global health crisis of our time. Elderly patients with certain fundamental diseases are more likely to develop severe cases. The secondary lesion following viral infection have only rarely been reported. CASE PRESENTATION: We here report two cases of coronavirus-infected pneumonia with acute ischemic stroke in middle-aged patients. In both COVID-19 cases, neurological physical examinations showed normal results before infection. Lymphocytopenia, accompanied by elevated cytokines and D-dimers, were found from serum clinical laboratory examination at admission. Dysarthria and limb muscle weakness are initial manifestations, occurring one week after infect-causative pathogen, SARS-CoV-2. The head CT and head/neck arterial CTA showed small-vessel occlusion. The patients were diagnosed with coronavirus diseases with secondary acute ischemic stroke. They were treated with tirofiban and followed up with daily aspirin and atorvastatin. CONCLUSIONS: These cases suggested that secondary ischemic stroke, mainly manifested as small-vessel occlusion, should be considered for COVID-19 patients and diagnosed and treated promptly.


Subject(s)
Brain Ischemia/etiology , COVID-19/complications , Ischemic Stroke/etiology , Aspirin/therapeutic use , Atorvastatin/therapeutic use , Brain Ischemia/drug therapy , Fibrinolytic Agents/therapeutic use , Humans , Ischemic Stroke/drug therapy , Male , Middle Aged , Pandemics , SARS-CoV-2 , Tirofiban/therapeutic use
12.
World Neurosurg ; 145: 356-359, 2021 01.
Article in English | MEDLINE | ID: covidwho-850856

ABSTRACT

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, a rapid screening method for COVID-19 detection is needed to decide the appropriate strategy to treat stroke patients. In acute ischemic stroke treatment, the efficacy and safety of emergent carotid artery stenting (eCAS) for hyperacute ischemic stroke (hAIS) due to internal carotid artery stenosis (ICS) have not been sufficiently established. CASE DESCRIPTION: A 71-year-old man with hAIS caused by severe ICS was treated via intravenous alteplase infusion. The patient underwent screening for COVID-19 by the loop-mediated isothermal amplification (LAMP) assay shortly after arrival at our institution. The LAMP result was obtained within 90 minutes, during intravenous alteplase infusion, and turned out to be negative. The symptom of hemiplegia worsened during alteplase infusion, and he, therefore, underwent eCAS after administration of aspirin (200 mg). Recanalization was achieved successfully by eCAS, and dual antiplatelet therapy and argatroban were administrated following eCAS. Hemorrhagic complications or restenosis/occlusion of the carotid artery were not observed. He was discharged without neurologic deficits 15 days following eCAS. Because of the rapid negative diagnosis for COVID-19 using the LAMP method, eCAS could be performed following standard procedures, along with infectious defense, without delay. CONCLUSIONS: This case report suggests that eCAS for hAIS due to ICS following intravenous alteplase can be an effective treatment, along with appropriate antiplatelet medication and management in select patients. During the COVID-19 pandemic, the LAMP assay for COVID-19 detection might be a suitable diagnostic strategy preceding stroke treatment because of the rapid turnaround time.


Subject(s)
COVID-19/diagnosis , Carotid Stenosis/surgery , Fibrinolytic Agents/therapeutic use , Ischemic Stroke/drug therapy , Ischemic Stroke/surgery , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , Stents , Tissue Plasminogen Activator/therapeutic use , Aged , Arginine/analogs & derivatives , Arginine/therapeutic use , Carotid Stenosis/complications , Carotid Stenosis/diagnostic imaging , Combined Modality Therapy , Hemiplegia/etiology , Humans , Ischemic Stroke/etiology , Magnetic Resonance Imaging , Male , Pipecolic Acids/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Sulfonamides/therapeutic use , Tomography, X-Ray Computed , Treatment Outcome
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