Mechanism of action and neuroprotective role of nicorandil in ischemic stroke.

Nicorandil is a dual mechanism anti-anginal agent that acts as a nitric oxide (NO) donor and a potassium (K+) channel opener. Recent studies have evaluated the effect of nicorandil on ischemic stroke. Neurons have a low tolerance to hypoxia and therefore the brain tissue is significantly vulnerable to ischemia. Current approved treatments for ischemic stroke are tissue plasminogen activators and clot retrieval methods. The narrow therapeutic time window and lack of efficacy in restoring the dying neurons urge researchers to develop an alternative approach. In the terminal stages of anoxia, K+ channels induce hyperpolarization in various types of neuronal cells, leading to decreased neuronal activity and the preservation of the brain's energy. Nicorandil can open these K+ channels and sustain the hyperpolarization phase, which may have a neuroprotective effect during hypoxia. Additionally, we review how nicorandil can improve overall stroke outcomes through its anti-inflammatory, anti-oxidative, and edema-reducing effects. One of the major components evaluated in stroke patients is blood pressure. Studies have demonstrated that the effect of nicorandil on blood pressure is related to both its K+ channel opening and NO donating mechanisms. Since both hypertension and hypotension need correction before stroke intervention, it's crucial to consider the role of nicorandil and its impact on blood pressure. Previously published studies indicate that the right dosage of nicorandil can improve cerebral blood flow without significant changes in hemodynamic profiles. In this review, we discuss how nicorandil may contribute to better stroke outcomes based on previously published literature and laboratory findings.

Quantitative EEG for the Monitoring of Walking Recovery in Chronic Stroke Patients Receiving Action Observation Training.

The current study aimed to evaluate the effects of action observation on the walking ability and oscillatory brain activity of chronic stroke patients. Fourteen chronic stroke patients were allocated randomly to the action observation (AO) or sham observation (SO) groups. Both groups received 12 sessions of intervention. Each session composed of 12 min of observational training, which depicted exercises for the experimental group but nature pictures for the sham group and 40 min of occupational therapy, which was the same for the both groups. Walking ability was assessed by a motion analysis system and brain activity was monitored using quantitative electroencephalography (QEEG) before and after the intervention. Brain asymmetry at alpha frequency, the percentage of stance phase, and step length showed significant changes in the AO group. Only the change in global alpha power was significantly correlated with the change in velocity after the intervention in AO group. Despite more improvements in walking and brain activity of patients in the AO group, our study failed to show significant correlations between the brain activity changes and functional improvements after the intervention, which might be mainly due to the small sample size in our study. Trial registration: IRCT20181014041333N1.

Cerebral venous thrombosis: a practical review.

The evolution of the Coronavirus Disease-2019 pandemic and its vaccination raised more attention to cerebral venous thrombosis (CVT). Although CVT is less prevalent than arterial stroke, it results in larger years of life lost. CVT is more common in women and young patients. Predisposing factors are categorized as transient factors such as pregnancy, puerperium, oral contraceptive pills, trauma, and dehydration; and permanent factors such as neoplastic, vasculitic, thrombophilic, hematologic conditions, infectious causes such as severe acute respiratory syndrome coronavirus-2 infection and HIV. The most common manifestations are headache, seizures, focal neurologic deficits, altered level of consciousness, and cranial nerve palsies. The most common syndromes are stroke-like, raised-intracranial-pressure (ICP), isolated-headache, and encephalopathy, which may have overlaps. Diagnosis is mostly based on computed tomography, magnetic resonance imaging, and their respective venous sequences, supported by blood results abnormalities such as D-dimer elevation. Treatment includes the prevention of propagation of current thrombus with anticoagulation (heparin, or low molecular weight heparinoids and then warfarin, or direct oral anticoagulants), decreasing ICP (even by decompressive craniotomy), and treatment of specific underlying diseases.

The role of transcranial direct current stimulation in diminishing the risk of pneumonia in patients with dysphagia: A double-blinded randomized clinical trial.

Background: Dysphagia can be a life-threatening issue for post-stroke patients, with aspiration pneumonia (AP) being a common risk. However, there is hope through the potential combination of transcranial direct current stimulation (tDCS) and classical behavior therapy. Our study aims to investigate the effectiveness of this combination in diminishing the risk of AP in patients with dysphagia who suffered from stroke. Methods: In this randomized, parallel-group, blinded clinical trial, 48 patients were allocated into the sham group (speech therapy + 30 seconds of tDCS) and the real group (speech therapy + 20 minutes of tDCS). We used the Mann Assessment of Swallowing Ability (MASA) as an assessment tool. We assessed patients at baseline, one day after treatment, and at a one-month follow-up. Results: Groups showed no significant difference at baseline. After treatment, the real group showed a significant difference in the severity risk of AP (P = 0.02); the same was for the follow-up (P = 0.04). The number of patients showing severe risk of AP was higher in the sham group after treatment (n = 13, 54.20%) and at follow-up (n = 4, 18.20%) than the real group (n = 4, 16.70%; n = 1, 4.50%, respectively). None of the patients reported the history of AP at any stage of assessment. Conclusion: Although the results were more promising in the real group than the sham group in reducing the risk of AP, both techniques can prevent AP. Therefore, we recommend early dysphagia management to prevent AP regardless of the treatment protocol.

Intracranial Atherosclerosis Disease Associated With Cognitive Impairment and Dementia: Systematic Review and Meta-Analysis.

BACKGROUND: Intracranial atherosclerosis disease (ICAD) alters cerebrovascular hemodynamics and brain structural integrity. Multiple studies have evaluated the link between ICAD and cognitive impairment, with mixed results. This study aims to systematically review and summarize the current evidence on this link. METHODS AND RESULTS: PubMed, EMBASE, PsycInfo, and Web of Science were searched from 2000 to 2023 without language restriction. Cross-sectional and prospective cohort studies as well as postmortem studies were included. Studies containing data on the link between ICAD, defined as at least 50% stenosis in 1 intracranial vessel, and cognitive impairment and dementia were screened by 2 independent reviewers. A total of 22 (17 observational and 5 postmortem) unique studies, comprising 11 184 individuals (average age range, 59.8-87.6 years; 45.7% women; 36.5% Asian race), were included in the systematic review. Seven of 10 cross-sectional studies and 5 of 7 prospective studies showed a significant association between ICAD and cognitive impairment. In the pooled analysis, ICAD was associated with greater cognitive impairment (measure of association, 1.87 [95% CI, 1.49-2.35]). Meta-regression analyses did not show a significant impact of age, sex, and race. All postmortem studies showed that patients with Alzheimer disease and vascular dementia had a higher burden of ICAD compared with controls. CONCLUSIONS: This study shows that ICAD is associated with cognitive impairment and dementia across age, sex, and race groups. Our findings may underscore the need to develop individualized dementia preventive care plans in patients with ICAD.

Combined use of hair follicle stem cells and CEPO (carbamylated erythropoietin)-Fc in a rat model of chronic cerebral hypoperfusion: A behavioral, electrophysiological, and molecular study.

BACKGROUND: In dementia, synaptic dysfunction appears before neuronal loss. Stem cell therapy could potentially provide a promising strategy for the treatment of dementia models. The carbamylated erythropoietin fusion protein (CEPO-Fc) has shown synaptotrophic effects. This study aimed to determine the efficiency of the combined use of hair follicle stem cells (HFSC) and CEPO-Fc in the basal synaptic transmission (BST) and long-term plasticity (LTP) of chronic cerebral hypoperfusion (CCH) rats. METHODS: We divided 64 adult rats into control, sham, CCH+vehicle, CCH+CEPO, CCH+HFSC, and CCH+HFSC+CEPO groups. The CEPO-Fc was injected three times/week for 30 days. HFSC transplantation was done on days 4, 14, and 21 after surgery. The Morris water maze test and passive avoidance were used to assess memory. BST and LTP were assessed by a field-potential recording of the CA1 region. The hippocampal mRNA expression of IGF-1, TGF-ß1, ß1-Catenine, NR2B, PSD-95, and GSk-3ß was evaluated by quantitative RT-PCR. RESULTS: Following combination therapy, spatial memory retention, and BST showed significant improvement relative to HFSC and CEPO-Fc groups. These effects were also confirmed by recovered mRNA expression of ß1-catenin, TGF-ß1, and NR2B. GSK-3ß expression was downregulated in all treatment groups. The upregulated PSD-95 was identified in HFSC and combination groups compared to the vehicle group. CONCLUSIONS: These findings indicate that the combined use of HFSC and CEPO-Fc may be more advantageous for treating memory disruption in the CCH model than CEPO-Fc or HFSC alone. This type of combination therapy may hopefully lead to a new approach to treatment for dementia.

Evaluating cognitive impairment in the early stages of Parkinson's disease using the Cambridge brain sciences-cognitive platform.

BACKGROUND: Non-motor symptoms (NMS) such as cognitive impairment are among common presentations in patients with Parkinson's disease (PD). In parallel with motor symptoms, these impediments can affect PD patients' quality of life. However, cognitive impairment has received less attention in early PD. On the other hand, the relationship between olfactory symptoms and cognitive impairment is unclear in early PD. Considering the importance of accurate and timely assessment of cognitive function in PD patients using readily available/validated tests, this study has employed the Cambridge Brain Sciences-Cognitive Platform (CBS-CP) as a computer-based tool to assess cognitive presentations in early PD patients. METHODS: Thirty-four eligible males and females were assigned to PD and healthy controls (HCs). The cognitive performance was assessed using CBS-CP and Mini-Mental State Examination (MMSE), and olfactory function was measured through the standardized olfactory Quick Smell test (QST). RESULTS: PD patients had poorer performance in all CBS-CP tasks, including short-term memory, attention, and reasoning domains than HCs. Meanwhile, the verbal domain task scores showed no significant difference between groups. PD MMSE results were in the normal range (mean=26.96), although there was a significant difference between the PD and HCs groups (P = 0.000). Our results revealed no correlation between cognitive impairment and olfactory function in PD patients. CONCLUSION: Given the widely studied features of CBS-CP and its reliability across published evidence, CBS-CP appears to be a suitable measurement to evaluate cognitive impairment in early PD with normal MMSE scores. It seems cognitive and olfactory impairments are independent in early PD. DATA AVAILABILITY STATEMENT: The datasets generated during the current study are available from the corresponding author upon reasonable request.

The hospitalization rate and clinical characteristics of mucormycosis prior and during COVID-19 pandemic: A single-center study.

INTRODUCTION: There have been some reports of the association between SARS-CoV-2 infection and mucormycosis. This study aims to compare the hospitalization rates and clinical characteristics of mucormycosis before and during the COVID-19 pandemic. METHODOLOGY: In this retrospective study, we compared the hospitalization rate of mucormycosis patients in Namazi hospital in Southern Iran for two periods of 40 months. We defined July 1st, 2018 to February 17th, 2020, as the pre-COVID-19 period and February 18th, 2020, to September 30th, 2021, as the COVID-19 period. In addition, a quadrupled group of hospitalized patients with age and sex-matched SARS-COV-2 infection without any sign of mucormycosis was selected as the control group for COVID-associated mucormycosis. RESULT: In the total of 72 mucormycosis patients in the COVID period, 54 patients had a clinical history and a positive RT-PCR, which confirms the diagnosis of SARS-COV2 infection. The hospitalization rate of mucormycosis showed an increase of + 306% (95% CI: + 259%, + 353%) from a monthly average value of 0.26 (95% confidence interval (CI): 0.14, 0.38) in the pre-COVID period to 1.06 in the COVID period. The use of corticosteroids prior to the initiation of hospitalization (p ≤ 0.01), diabetes (DM) (p = 0.04), brain involvement (p = 0.03), orbit involvement (p = 0.04), and sphenoid sinus invasion (p ≤ 0.01) were more common in patients with mucormycosis during the COVID period. CONCLUSIONS: In high-risk patients, especially diabetics, special care to avoid the development of mucormycosis must be taken into account in patients with SARS-COV-2 infection considered for treatment with corticosteroids.

Increased Serum Levels of IL-1ß after Ischemic Stroke are Inversely Associated with Vitamin D.

Background: The initial inflammatory reaction starts following occlusion in ischemic stroke (IS). Interleukin-1ß (IL-1ß) is a pro-inflammatory cytokine with a crucial role in the pathogenesis of neurodegenerative disorders. Objective: To investigate the levels of IL-1ß and vitamin D (VitD) in patients with IS compared with controls and their correlation. Methods: The serum level of 25-OH VitD and IL-1ß was assessed in 102 IS patients (0-24 h after stroke) and 102 controls with an enzyme-linked immunosorbent assay (ELISA) kit. Results: We found a significant increase in IL-1ß (80.14±6.8 vs. 60.32±4.1 pg/ml, p<0.05) and a decrease in VitD level (24.3±1.4 vs. 29.9±1.5 ng/ml, p<0.01) in the IS patients compared with the controls. There was a significantly positive correlation between the National Institutes of Health Stroke Scale (NIHSS) and IL-1ß according to both the Spearman correlation (r=0.35, p=0.0003) and the linear regression (beta=0.255, p=0.014). Also, a significant negative association between VitD and NIHSS was detected by the Spearman correlation (r=-0.41, p<0.0001) and the linear regression (beta=-0.381, p=0.000). Moreover, we found a significant negative correlation (r=-0.26, p=0.006) between the serum levels of VitD and IL-1ß in the patient group. Conclusion: Ischemic stroke correlates positively with IL-1ß and negatively with VitD levels. The speculated role of VitD deficiency in the evolution and severity of stroke may be justified by its role in the modification of inflammation.

Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19.

INTRODUCTION: Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. PATIENTS AND METHODS: We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. RESULTS: Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28-54) vs 45 (28-56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x109/L (28-79) vs 68 (30-125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19-62) vs 53 (20-92)]. More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. DISCUSSION AND CONCLUSIONS: Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment.

Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia in middle-income countries.

BACKGROUND: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. AIMS: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. METHODS: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). RESULTS: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteria, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20-37) versus 47 (IQR 32-58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11-40]) than in HICs (44/102 [43%, 95% CI 34-53], p = 0.039). CONCLUSIONS: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.

Effect of Non-Ablative Non-Thermal CO2 Laser on Drug-Resistant Trigeminal Neuralgia: A Pilot Study.

Background: Trigeminal neuralgia is one of the most severe pain conditions that humans experience. Drug resistance is a challenging event during treatment that results in using higher doses of drugs or referring for neurosurgical treatment. Laser therapy is also an effective method for pain control. Objective: The aim of this study was to evaluate the effect of non-ablative non-thermal CO2 laser (NANTCL) on reducing pain in patients with drug-resistant trigeminal neuralgia (DRTN) for the very first time. Materials and methods: Twenty-four patients with DRTN were randomly divided into laser and placebo groups. Patients in the laser group received NANTCL (10,600 nm, 1.1 W, 100 HZ, 20 sec) on trigger points that were covered with lubricant gel 3 days in a week for 2 weeks. The placebo group received sham laser. The patients were requested to grade their pain on a visual analog scale (VAS) immediately, 1 week, 1 month, and 3 months after treatment. Results: In the laser group, the results revealed a significant decrease between the initial pain and the pain in all follow-up sessions. Only in three patients, 3 months after completion of laser therapy, pain returned to the initial level. In the control group, a significant difference was seen only between the pain of baseline and final session of laser irradiation. In laser group, the mean of pain (VAS) was lower than the placebo group in all follow-up sessions; however, it was only significant for 1 week after laser therapy. Conclusions: This study revealed that short-period application of NANTCL is effective for pain relief in patients with DRTN, especially those with extraoral trigger points. Clinical trial registration number: IRCT2013052113406N1.

Short-term beneficial effects of human dental pulp stem cells and their secretome in a rat model of mild ischemic stroke.

Although cell therapy has been applied in regenerative medicine for decades, recent years have seen greatly increased attention being given to the use of stem cell-based derivatives such as cell-free secretome. Dental pulp stem cells (DPSCs) are widely available, easily accessible, and have high neuroprotective and angiogenic properties. In addition, DPSC-derived secretome contains a rich mixture of trophic factors. The current investigation evaluated the short-term therapeutic effects of human DPSCs and their secretome in a rat model of mild ischemic stroke. Mild ischemic stroke was induced by 30 min middle cerebral artery occlusion, and hDPSCs or their secretome was administered intra-arterially and intranasally. Neurological function, infarct size, spatial working memory, and relative expression of seven target genes in two categories of neurotrophic and angiogenic factors were assessed three days after stroke. In the short-term, all treatments reduced the severity of neurological and histological deficits caused by ischemic stroke. Moreover, transient middle cerebral artery occlusion led to the striatal and cortical over-expression of BDNF, NT-3, and angiogenin, while NGF and VEGF expression was reduced. Almost all interventions were able to modulate the expression of target genes after stroke. The obtained data revealed that single intra-arterial administration of hDPSCs or their secretome, single intranasal transplantation of hDPSCs, or repeated intranasal administration of hDPSC-derived secretome was able to ameliorate the devastating effects of a mild stroke, at least in the short-term.

Mechanism of action and therapeutic potential of dimethyl fumarate in ischemic stroke.

Dimethyl fumarate (DMF) is an immunomodulatory drug currently approved for the treatment of multiple sclerosis and psoriasis. Its benefits on ischemic stroke outcomes have recently come to attention. To date, only tissue plasminogen activators (tPAs) and clot retrieval methods have been approved by the FDA for the treatment of ischemic stroke. Ischemic conditions lead to inflammation through diverse mechanisms, and recanalization can worsen the state. DMF and the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) pathway it regulates seem to be important in postischemic inflammation, and animal studies have demonstrated that the drug improves overall stroke outcomes. Although the exact mechanism is still unknown, studies indicate that these beneficial impacts are due to the modulation of immune responses, blood-brain barrier permeability, and hemodynamic adjustments. One major component evaluated before, during, and after tPA therapy in stroke patients is blood pressure (BP). Recent studies have found that DMF may impact BP. Both hypotension and hypertension need correction before treatment, which may delay the appropriate intervention. Since BP management is crucial in managing stroke patients, it is important to consider DMF's role in this matter. That being said, it seems further investigations on DMF may lead to an alternative approach for stroke patients. In this article, we discuss the mechanistic roles of DMF and its potential role in stroke based on previously published literature and laboratory findings.

Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND AND PURPOSE: Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. CVST-VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST-VITT patients who underwent decompressive surgery are described and predictors of in-hospital mortality in these patients are explored. METHODS: Data from an ongoing international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680-1689), were included. RESULTS: Decompressive surgery was performed in 34/128 (27%) patients with CVST-VITT. In-hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non-surgical group (p < 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non-comatose; p < 0.001) and bilaterally absent pupillary reflexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bilaterally reactive pupils; p = 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) patients. At a median follow-up of 6 months, 8/10 of surgical CVST-VITT who survived admission were functionally independent. CONCLUSIONS: Almost two-thirds of surgical CVST-VITT patients died during hospital admission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence.

Outcome predictors in anterior and posterior ischemic strokes: a study based on the Iranian SITS registry.

Ischemic stroke is the major form of stroke with two separate vascular territories. Many risk factors are related to stroke outcomes in both territories. The present descriptive research was carried out on the basis of data obtained from the Safe Implementation of Treatments in Stroke (SITS) registry on Iranian intravenous thrombolysis ischemic stroke cases. Vascular territory involved in each case and three-month excellent outcome, functional independence, mortality rate, and brain hemorrhage occurrence were determined. Univariable and multivariable logistics regression analyses were utilized in order to investigate association of ischemic stroke outcomes with the vascular territory involved and other related factors. Among 1566 patients 95.4% was anterior circulation stroke patients and 4.6% was posterior circulation stroke cases. There is no significant association between vascular territory with mortality (OR of PCS vs ACS: 0.74, 95% CI 0.37-1.46), excellent functional outcome (OR 0.72, 95% CI 0.44-1.19), functional outcome (OR 0.86, 95% CI 0.52-1.42) and local hemorrhage (OR 0.98, 95% CI 0.30-3.21). Among major risk factors, age, diabetes, NIHSS score and admission duration, increased significantly odds of three-month mortality, excellent outcome, and functional independence in the multivariate analysis. The highest of odds was in NIHSS score with a dose-response association. The vascular territory was not an outcome predictor in ischemic strokes. The most important predictor was baseline NIHSS.

The beneficial effects of chick embryo extract preconditioning on hair follicle stem cells: A promising strategy to generate Schwann cells.

The beneficial effects of hair follicle stem cells in different animal models of nervous system conditions have been extensively studied. While chick embryo extract (CEE) has been used as a growth medium supplement for these stem cells, this is the first study to show the effect of CEE on them. The rat hair follicle stem cells were isolated and supplemented with 10% fetal bovine serum plus 10% CEE. The migration rate, proliferative capacity and multipotency were evaluated along with morphometric alteration and differentiation direction. The proteome analysis of CEE content identified effective factors of CEE that probably regulate fate and function of stem cells. The CEE enhances the migration rate of stem cells from explanted bulges as well as their proliferation, likely due to activation of AP-1 and translationally controlled tumour protein (TCTP) by thioredoxin found in CEE. The increased length of outgrowth may be the result of cyclic AMP response element binding protein (CREB) phosphorylation triggered by active CamKII contained in CEE. Further, CEE supplementation upregulates the expression of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. The elevated expression of target genes and proteins may be due to CREB, AP-1 and c-Myc activation in these stem cells. Given the increased transcript levels of neurotrophins, VEGF, and the expression of PDGFR-α, S100B, MBP and SOX-10 protein, it is possible that CEE promotes the fate of these stem cells towards Schwann cells.

From Hair to the Brain: The Short-Term Therapeutic Potential of Human Hair Follicle-Derived Stem Cells and Their Conditioned Medium in a Rat Model of Stroke.

The short-term therapeutic impacts of stem cells and their derivatives were frequently reported in preclinical investigations of ischemic stroke (IS); however, several drawbacks including accessibility, abundancy, and ethical concerns limited their clinical application. We describe here for the first time the therapeutic potential of human hair follicle-derived stem cells (hHFSCs) and their conditioned medium (CM) in a rat model of IS. Furthermore, we hypothesized that a combination of cell therapy with repeated CM administration might enhance the restorative efficiency of this approach compared to each treatment alone. Middle cerebral artery occlusion was performed for 30 min to induce IS. Immediately after reperfusion, hHFSCs were transplanted through the intra-arterial route and/or hHFSC-CM administered intranasally. The neurological outcomes, short-term spatial working memory, and infarct size were evaluated. Furthermore, relative expression of seven target genes in three categories of neuronal markers, synaptic markers, and angiogenic markers was assessed. The hHFSCs and hHFSC-CM treatments improved neurological impairments and reduced infarct size in the IS rats. Moreover, molecular data elucidated that IS was accompanied by attenuation in the expression of neuronal and synaptic markers in the evaluated brain regions and the interventions rescued these expression changes. Although there was no considerable difference between hHFSCs and hHFSC-CM treatments in the improvement of neurological function and decrement of infarct size, combination therapy was more effective to reduce infarction and elevation of target gene expression especially in the hippocampus. These findings highlight the curative potential of hHFSCs and their CM in a rat model of IS.

Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: A Systematic Review of Economic Evaluations.

OBJECTIVES: Several studies have evaluated the economic evaluation of a group of medications known as novel oral anticoagulant drugs (NOACs) in recent years. The aim of this study is to review and systematically analyze the cost-utility studies results of warfarin compared with other NOAC drugs in atrial fibrillation patients. METHODS: A systematic review was performed to identify all studies evaluating the NOAC medications in comparison with warfarin. For this purpose, PubMed, Cochrane Library, ISI Web of Science, and Scopus were searched from 2013 to 2022. Articles were independently screened with inclusion criteria, and full texts were reviewed. First, the Consolidated Health Economic Evaluation Reporting Standards checklist was used to evaluate the quality of the articles. Then, the costs and outcomes of the studies were analyzed, and findings were appraised critically. RESULTS: A total of 84 costs-per-quality-adjusted life-year (QALY) cases were extracted from the studies in which the share of rivaroxaban, edoxaban, apixaban, and dabigatran were 31%, 13%, 29%, and 27%, respectively. The median cost per QALY of rivaroxaban, edoxaban, apixaban, and dabigatran was 21 910$/QALY, 22 096$/QALY, 17 765$/QALY, and 24 161$/QALY, respectively. Subgroup analysis based on perspective showed that dabigatran had the highest incremental cost-effectiveness ratio (ICER) and edoxaban had the lowest ICER value. Edoxaban and apixaban had the highest and the lowest cost per QALY from an insurance perspective, respectively. CONCLUSION: Despite the differences and variations in the economic evaluation studies of NOAC drugs, these drugs have shown acceptable cost-effectiveness in developed and developing countries. Among NOAC drugs, apixaban has the lowest ICER and the highest cost-effectiveness.

Comparison of Commercial Low Molecular Weight Heparin and Homemade Anti-Xa Calibrators to a Commercial Specific Anti-Xa Calibrator for Plasma Rivaroxaban Quantification by Anti-Xa Oral Anticoagulant Plasma Concentration Chromogenic Assay.

OBJECTIVE: The main concern about measuring the concentration of rivaroxaban by anti-Xa assay in some laboratories is the lack of a commercial specific calibrator in emergencies. Therefore, this study aimed at providing a homemade anti-Xa calibrator and commercial low molecular weight heparin (LMWH) anti-Xa calibrator. METHODS: The anti-Xa plasma concentration of rivaroxaban was measured in 70 patients using a commercial specific anti-Xa calibrator, a commercial LMWH anti-Xa calibrator, and a homemade anti-Xa calibrator. RESULTS: We demonstrated a significant correlation and agreement (P < .001) between LMWH-calibrated anti-Xa and the commercial specific calibrator. A significant correlation (P < .001) was found between homemade calibrated anti-Xa made by normal pooled plasma and that calibrated with a commercial specific drug. The nonspecific homemade and LMWH calibrators had excellent agreement (P < .001) and can be used interchangeably. CONCLUSION: Our data showed that for estimating rivaroxaban concentrations, the LMWH calibrator could be used as an alternative calibrator in the anti-Xa assay.