afshin borhani-haghighi
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Background
Inflammation is the major contributor to the pathophysiology of ischemic stroke (IS). Long non-coding ribonucleic acids (lncRNAs) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and tumor necrosis factor and heterogeneous nuclear ribonucleoprotein L-related immunoregulatory (THRIL) have been demonstrated to be up-regulated in inflammation and atherosclerosis. Therefore, we aimed to study the expression profile of these lncRNAs after IS.
MethodsThis observational case-control study was conducted in Namazi Hospital, Shiraz, Iran. The real-time polymerase chain reaction (RT-PCR) measured the sequential changes in circulating levels of MALAT1 and THRIL on days 1, 3, and 5 after IS. The receiver operating characteristic (ROC) curve analysis was used to estimate the diagnostic and prognostic potential of lncRNAs with the area under the curve (AUC).
ResultsIn patients with IS, the relative MALAT1 and THRIL expressions were significantly higher than the controls (P < 0.001 and P < 0.01, respectively), on days 1, 3, and 5 after stroke. We showed a significantly increase in lncRNAs expression on day five compared to days 1 and 3 after stroke. Moreover, a positive correlation was detected between MALAT1 expression and time within the first 24 hours after stroke (r = 0.27, P = 0.03). Logistic regression analysis showed a significant positive association between MALAT1 and THRIL and the risk of stroke evolution. We found a potential diagnostic marker for MALAT1 with an AUC of 0.78.
ConclusionWe demonstrated the significant sequential upregulation in MALAT1 and THRIL expression on days 1, 3, and 5 after IS with a significant positive association with the risk of stroke. MALAT1 also significantly correlated with time within the first 24 hours after stroke.
Keywords: Long Noncoding RNA, MALAT1 Long Noncoding RNA, THRIL Long Noncoding RNA, Ischemic Stroke -
Background
Cell therapy, involving the transplantation of viable cells for therapeutic purposes, offers immense promise but faces challenges related to cell survival and functionality post-transplantation. Preconditioning strategies, particularly hypoxic preconditioning, have emerged as a means to enhance cell adaptability and resilience.
ObjectivesThis study investigated the impact of hypoxic preconditioning on the survival and oxidative stress tolerance of nestin-expressing hair follicle stem cells (hHFSCs) and SH-SY5Y neuroblastoma cells, two crucial cell types for central nervous system therapies. The study also examined the relative expression of three key genes, HIF1α, BDNF, and VEGF following hypoxic preconditioning.
Materials and MethodshHFSCs were isolated from human hair follicles, characterized, and subjected to hypoxia for up to 72 hours. SH-SY5Y cells were similarly preconditioned for up to 72 hours. Cell viability under hypoxic conditions and oxidative stress was assessed. The relative expression of key genes was evaluated using qRT-PCR.
ResultshHFSCs exhibited remarkable resilience to hypoxic conditions, while SH-SY5Y cells displayed lower tolerance. Hypoxic preconditioning improved the viability of both cell types under oxidative stress. HIF1α mRNA was significantly downregulated, and VEGF transcripts increased after preconditioning, suggesting adaptations to prolonged hypoxia.
ConclusionHypoxic preconditioning enhances the survival and oxidative stress resilience of hHFSCs and SH-SY5Y cells, offering potential benefits for central nervous system cell therapy. The differential responses observed emphasize the need for tailored preconditioning strategies for specific cell types. These findings underscore the importance of hypoxic preconditioning and warrant further research into the underlying mechanisms, bringing us closer to effective neurological disorder treatments.
Keywords: EPI-Ncscs, HAP Stem Cells, Hypoxia, Priming -
Background
Previous studies have demonstrated the strong association of inflammatory cytokines and vitamin D (VitD) deficiency and ischemic stroke (IS) pathogenesis. Due to the negative correlation between long non-coding RNA (lncRNA) Malat1 and pro-inflammatory factors we decided to investigate the associations between Malat1 expression with serum interleukin-1β (IL-1β), and VitD levels in IS patients.
Materials and MethodsIn this cross-sectional study, 63 IS patients were included. We used enzyme-linked immunosorbent assays to evaluate the serum levels of VitD and IL-1β. Malat1 expression was evaluated by the real-time polymerase chain reaction test. The associations between Malat1expression with VitD and IL-1β were analysed with linear regression (Stepwise model) and Pearson’s correlation analysis.
ResultsThe Malat1 expression was inversely correlated with stroke severity (r=-0.25, P=0.043). Stepwise regression analysis showed a significant positive relationship between VitD level and Malat1 expression (Beta=0.28, P=0.02), and also showed a non-significant negative relationship between IL-1β and stroke severity. VitD level showed a positive Pearson correlation with Malat1 (r=0.28, P=0.023) and a negative correlation with IL-1β (r=-0.29, P=0.018) while it could not detect a significantly negative correlation with stroke severity.
ConclusionFor the first time the associations between Malat1 expression with IL-1β and VitD in IS patients was analyzed. We found a significant positive relationship between VitD and Malat1. This correlation needs to be investigated with a larger sample size to achieve a strong and reliable association between VitD and Malat1.[GMJ.2023;12:e2457]
Keywords: Long Non-coding RNA, Malat1, nterleukin-1 Beta, Vitamin D, Ischemic Stroke -
Background
Fast diagnosing ischemic stroke (IS) is a critical issue in clinical studies, as it allows more effective therapy and stops the progression of IS. The blood level of circular RNAs (CircRNAs) after stroke may be a rapid diagnostic marker.
MethodsIn this study, the blood level of circRNAs was evaluated using a real-time polymerase chain reaction (PCR). We used logistic and linear regression analysis to assess the potential of circRNAs levels with the risk of IS.
ResultscircRNA DLG associated protein 4 (CircDLGAP4) was decreased in patients compared with controls, and logistic regression showed its expression negatively associated with IS risk. The expression level of human genome version 38_Circular_0008980 (hg38_circ_0008980) was reduced significantly in patients with small vessel disease (SVD), and the linear regression analysis showed a negative relationship between hg38_circ_0008980 expressions with SVD subtype. hg38_circ_0008980 expression relative to controls showed a significant association with IS risk.
ConclusionsTaken together, we found a significant decrease in the level of hg38_circ_0008980 after IS; it may act as a novel circRNA in IS pathophysiology with a positive correlation with stroke severity.
Keywords: Biomarkers, Circular RNAs, Ischemic strokes -
Objective
Genetic aspects can play an essential role in the occurrence and development of ischemic stroke (IS).Rs1894720 polymorphism is one of the eight single nucleotide polymorphisms (SNPs) in the long non-coding RNA(lncRNA) myocardial infarction-associated transcript (MIAT) locus. The aim of study is the lncRNA MIAT rs1894720polymorphism decreases IS risk by reducing lncRNA MIAT expression.
Materials and MethodsIn this case-control study, we studied 232 Iranian patients and 232 controls. The blood sampleswere collected from patients admitted at different times after stroke symptoms. We enrolled 80, 78, and 74 patientswho arrived at the hospital between 0-24, 24-48, and 48-72 hours after the first appearance of symptoms, respectively.DNA genotyping was done by the tetra-primer ARMS-PCR method. Circulating MIAT levels were evaluated by real-timepolymerase chain reaction (PCR).
ResultsThe GT genotype of MIAT rs1894720 showed a significant association with the risk of IS (OR=3.53, 95%CI=2.13-5.84, P<0.001). MIAT expression was higher relative to the control within the first hours after IS. The MIATlevels in IS patients with rs1894720 (GT) were significantly lower relative to patients who had the GG and TT genotypes.Linear regression model indicated a significant correlation between MIAT expression with atherosclerotic risk factorsand types of stroke in IS patients. Receiver operating characteristic (ROC) curve analysis showed that the level oflncRNA MIAT after IS could be diagnostic with an area under the curve (AUC) of 0.82. The sensitivity and specificitywere 80.17 and 67.24%, respectively (P<0.001).
ConclusionOur study demonstrated that the MIAT rs1894720 polymorphism (GT) might increase the risk of IS in theIranian population. MIAT expression was up-regulated in our IS patients. Hence, it could be a diagnostic biomarker for IS.
Keywords: Biomarkers, Gene expression, Long Non-Coding RNA -
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.
MethodsIn 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.
ResultsGroups 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.
ConclusionAlthough 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.
Keywords: Deglutition, Stroke, Electrical Stimulation, Transcranial Direct Current Stimulation, Randomized Clinical Trial, Dysphagia, Pneumonia -
Background
The initial inflammatory reaction starts following occlusion in ischemic stroke (IS). Interleukin-1β (IL-1β) is a pro-inflammatory cytokine with a crucial role in the pathogenesis of neurodegenerative disorders.
ObjectiveTo investigate the levels of IL-1β and vitamin D (VitD) in patients with IS compared with controls and their correlation.
MethodsThe serum level of 25-OH VitD and IL-1β was assessed in 102 IS patients (0-24 h after stroke) and 102 controls with an enzyme-linked immunosorbent assay (ELISA) kit.
ResultsWe found a significant increase in IL-1β (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-1β 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-1β in the patient group.
ConclusionIschemic stroke correlates positively with IL-1β 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.
Keywords: Inflammation, Interleukin-1β, ischemic stroke, Vitamin D -
Background
Transient global amnesia (TGA) is a sudden-onset transient memory impairment along with intact neurologic examinations. Even though it is a benign neurologic condition with many differential diagnoses, the incidence rate of TGA is reported to have increased since the onset of the pandemic. Therefore, this systematic scoping review aims to investigate TGA in that context.
MethodsMEDLINE, Scopus, and Google Scholar databases were systematically searched for relevant articles with a string of specified keywords.
ResultsThe primary search yielded 90 studies. After all the necessary screening rounds were carried out, we were left with six included studies. One study was also identified through a search in other relatively relevant databases. Finally, seven case reports were accepted including three TGA patients with positive and one with negative test for coronavirus disease-2019 (COVID-19), respectively. COVID-19 status was unclear in the others.
ConclusionThe reported COVID-19 positive cases had presentations similar to those with TGA before the pandemic. Therefore, we think that TGA might occur concomitantly with the COVID-19 infection or due to the psychological impact of the pandemic. In the confirmed cases of TGA and COVID-19, the abnormal findings may be due to COVID-19 infection. However, the reports were not as complete as desired. Therefore, providing the readers with more detailed reports in future cases is recommended.
Keywords: Transient Global Amnesia, Coronavirus, Covid-19, SARS-CoV-2 -
Introduction
Vitamin D deficiency has been linked to the evolution of ischemic stroke, but the data regarding the association between stroke severity and vitamin D level is scarce.
MethodsPatients with first-ever ischemic stroke in the middle cerebral artery territory, within seven days after the stroke, were recruited. The control group included age- and gender-matched individuals. We compared 25-OH vitamin D (vitamin D), high sensitive C-reactive protein (hsCRP), serum amyloid A (SAA), and osteopontin levels between stroke patients and the control group. The association between stroke severity according to the National Institutes of Health Stroke Scale (NIHSS) and the Alberta stroke program early CT score (ASPECTS) and levels of vitamin D and inflammatory biomarkers were also studied.
ResultsThere was an association between hypertension (P=0.035), diabetes mellitus (P=0.043), smoking (P=0.016), history of ischemic heart disease (P=0.002), higher SAA (P<0.001), higher hsCRP (P<0.001), and lower vitamin D levels (P=0.002) and stroke evolution in a case-control study. Meanwhile, in stroke patients, its severity was associated with higher SAA (P=0.04) and hsCRP (P=0.001), and lower vitamin D levels (P=0.043) according to clinical scale (higher admission NIHSS). According to the ASPECT score, higher SAA (P=0.017) and hsCRP (P=0.007), but not lower vitamin D levels, were associated with more infarct areas (P=0.149).
ConclusionVitamin D may play a role in both the evolution and severity of stroke.
Keywords: Ischemic stroke, Cerebrovascular accident, Vitamin D, High sensitive C-reactive protein, Serum Amyloid A, Osteopontin -
Stroke-related atrial fibrillation (AF), deep vein thrombosis (DVT), and pulmonary thromboembolism (PE) are among the most common thromboembolic events. recently, direct oral anticoagulants (DOACs) have been slowly replacing warfarin. Rivaroxaban is a DOAC frequently prescribes to control thrombotic events. The safety and efficacy of Rivaroxaban are dependent on appropriate prescription, dosage, and other factors. This study is aimed to evaluate the Rivaroxaban utilization based on the standard protocol in both inpatient and outpatient settings. This cross-sectional/observational study was conducted for six months from 1st August 2018 to 1st February 2019 at a private hospital and also an outpatient clinic in Shiraz, Iran. First, a clinical pharmacist defined a standard protocol for Rivaroxaban utilization and several indexes (9 indexes for Non-valvular AF (NVAF) patients and 10 indexes for DVT/PE patients). Second, participants were classified into three groups (NVAF inpatients, NVAF outpatients, and DVT/PE patients). Finally, the adherence of Rivaroxaban utilization indexes in each group to was evaluated accordingly. Two hundred and forty one eligible patients were recruited into this study. Most patients (N=208), were NVAF. Rivaroxaban utilization was appropriate in 71.9%, 65.8%, and 50.6% of patients within groups 1, 2, and 3, respectively. Although medication interaction, administration regarding time/meal, and dose adjustment based on renal function showed the lowest compliance, the monitoring laboratory data and considering the underlying disorders were completely matched with the protocol. This study showed some critical errors in both settings, especially in DVT/PE patients (49.4% no match). Hence, the most productive collaboration must be developed between clinical pharmacists and clinical practitioners.
Keywords: Atrial fibrillation, Anticoagulants, Venous Thromboembolism, Pulmonary Thromboembolism, Rivaroxaban -
BackgroundRemote ischemic preconditioning (RIPC) has been proposed as a possible potential treatment for ischemic stroke. This study aimed to investigate the frequency of micro-embolic brain infarcts after RIPC in patients with stroke who underwent elective carotid artery stenting (CAS) treatment.MethodsThis study was managed at Shiraz University of Medical Sciences in southwest Iran. Patients undergoing CAS were randomly allocated into RIPC and control groups. Patients in the RIPC group received three intermittent cycles of 5-minute arm ischemia followed by reperfusion using manual blood cuff inflation/deflation less than 30 minutes before CAS treatment. Afterward, stenting surgery was conducted. Magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC), was acquired within the first 24 hours after CAS.ResultsSeventy-four patients were recruited (79.7% men, age: 72.30 ± 8.57). Both groups of RIPC and control had no significant difference in baseline parameters (P > 0.05). Fifteen patients (40.5%) in the RIPC group and 19 (54.1%) patients in the control group developed restricted lesions in DWI MRI. In DWI+ patients, there were no significant differences according to the number of lesions, lesion surface area, largest lesion diameter, cortical infarcts percent, and ipsilateral and bilateral infarcts between the two groups.ConclusionAlthough RIPC is a safe and non-invasive modality before CAS to decrease infarcts, this study did not show the advantage of RIPC in the prevention of infarcts following CAS. It may be because of the small sample size.Keywords: Ischemic Preconditioning, Stroke, Carotid Arteries, Stents, Brain Infarction, Angioplasty
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Introduction
Aneurysm formation of internal carotid arteries (ICA) in patients with mucormycosis is a scarce phenomenon. However, the prevalence of rhino-cerebral mucormycosis has been reported to increase after the Coronavirus disease 2019 (COVID-19) pandemic.
Case PresentationThree patients with stroke and subarachnoid hemorrhage presented due to ICA aneurysm after the involvement of adjacent paranasal sinuses (PNS) with mucormycosis. They had a history of diabetes and corticosteroid use. Also, one of them was treated with imatinib. Two out of the three patients were infected with SARS-CoV-2 before developing mucormycosis. Two patients had diagnostic angiography before endovascular intervention. One patient did not undergo any therapeutic intervention due to total artery occlusion, whereas the other patient experienced a successful parent artery occlusion by coiling and only survived this patient. Although all patients received antifungal treatment and surgical debridement, two of them died.
ConclusionsIn patients with rhino-cerebral mucormycosis, aneurysm evolution should be promptly and meticulously investigated by Magnetic Resonance Angiography (MRA) and Computed Tomography Angiography (CTA). As this type of aneurysm is very fast-growing, as soon as the involvement of the sphenoid sinus is detected, the possibility of ICA aneurysm formation should always be kept in mind. If the patient develops an aneurysm, prompt intensive antifungal therapy and therapeutic endovascular interventions such as stenting, coiling, or sacrificing should be considered as soon as possible to optimize outcomes.
Keywords: Rhino-cerebral Mucormycosis, Internal Carotid Artery, Mucormycosis, Aneurysm -
Introduction
Otorrhagia is not a common manifestation of petrous internal carotid artery (ICA) aneurysm. Besides idiopathic cases, different etiologies, including trauma, infection, and radiation, have been suggested for petrous ICA aneurysms/pseudoaneurysms. However, there is limited experience in the management of this rare aneurysm/pseudoaneurysm with coil embolization.
Case PresentationA 58-year-old man, who was a known case of chronic otitis media, was referred from the otorhinolaryngology ward with intractable bleeding from the right ear. A pseudoaneurysmal lesion (7 mm × 5 mm) was detected in the petrous segment of the internal carotid artery. The patient underwent coil embolization with no complications.
ConclusionTo the best of our knowledge, this is the first case of petrous ICA pseudoaneurysm, presenting with only intractable otorrhagia. The patient was successfully treated with coil embolization, with no need for further interventions. Besides, a review of petrous ICA aneurysms or pseudoaneurysms presenting with otorrhagia was performed.
Keywords: Endovascular Treatment, Otorrhagia, Interpetrosal Internal Carotid Artery Pseudoaneurysm, Coil Embolization -
Introduction
Stem cell therapy is considered as a promising strategy to treat neurological disorders. Amongst different cell types that are recruited under these devastating conditions, epidermal neural crest stem cells (EPI-NCSCs) are known as potential candidates. Acetylsalicylic acid (ASA or aspirin) is one of the commonly prescribed drugs that might affect the therapeutic potential of the transplanted stem cells. Hence, the present study aimed to evaluate the effects of ASA on the expression of fundamental growth factors involved in restorative pathways expressed by EPI-NCSCs in vitro for possible combination therapy’s purpose.
MethodsEPI-NCSCs were obtained from the rat’s hair follicle. The appropriate ASA concentration to treat the cells was defined based on the MTT assay and then the obtained cells were treated with 80 or 800µM ASA for 1, 3 or 7 days. The relative expressions of Bdnf, Gdnf, Ngf, Neurotrophin-3, Vegf, Gfap, and doublecortin were finally assessed by qRT-PCR.
ResultsThe obtained data revealed that the growth factors expressions are influenced by concentration and duration of the treatment applied. One-day ASA treatment was found to be able to increase the expression of all the evaluated genes, except Gdnf and doublecortin, which elevated three days later. Herein, seven-day treatment of stem cells with 800µM ASA resulted in higher levels of Bdnf, Vegf, and doublecortin.
ConclusionTherefore, combination of aspirin and EPI-NCSCs might increase the therapeutic potential of these stem cells to treat neurological disorders.
Keywords: Aspirin, ASA, EPI-NCSCs, Growth factors, Neurological disorders -
Major Dietary Patterns Are Associated with Acute Ischemic StrokeBackground
Dietary patterns play an essential role in vascular diseases; however, the association of specific dietary patterns and the risk of stroke is unknown. We designed the current study to evaluate several dietary patterns and their association with ischemic stroke.
Materials and MethodsThis case-control study was performed on 300 subjects, including 150 cases with ischemic stroke admitted to a tertiary referral center in Shiraz, Southern Iran, and 150 age- and sex-matched stroke-free individuals as controls. Using a 62-item Simple Stroke Food Frequency Questionnaire (SS-FFQ), we collected data regarding the dietary habits of all the participants. We extracted the major dietary patterns via principal component analysis using the varimax rotation technique with Kaiser Normalization. Finally, adherence to dietary patterns among the participants was divided into quartiles. We investigated the association between dietary patterns and ischemic stroke using multiple logistic regression analyses.
ResultsOne-hundred and fifty ischemic stroke patients (91 males and 59 females, mean age of 63.9±16.04 years) and 150 age- and sex-matched controls (91 males and 59 females, mean age of 61.99±16.04 years) were included. After adjusting five major dietary patterns for vascular risk factors, we found that diets rich in fibers and plant-based proteins (P<0.001) and micronutrients (P<0.001) had a lower odds of ischemic stroke as compared to high-fat proteins (P=0.003) and empty calories (P<0.001) diets, but consuming healthy animal proteins (P=0.115) had no effects on the occurrence of ischemic stroke.
ConclusionBased on our study, we suggest that fibers and plant-based proteins, and micronutrient diets could reduce the odds of stroke, so public awareness about the effects of different dietary patterns should be raised.
Keywords: Dietary pattern, Diet, Nutrition, Ischemic stroke -
BackgroundNeurological disability associated with multiple sclerosis and immunosuppressive or immunomodulatory therapy which is administered for it may increase the risk of SARS-CoV-2 infection and its morbidity/mortality.In this study, we evaluated the severity of SARS-CoV-2 infection in patients with multiple sclerosis based on their demographic and disease data.MethodsA total of 1361 multiple sclerosis patients from Fars province were interviewed by phone from April 3 to June 20, 2020. Basic demographic data, information about their disease and any symptoms or laboratory results relevant to COVID-19 were gathered.ResultsAmong the studied patients, 68 ones (5%) were COVID-19 suspected cases and 8 ones (0.58%) were in the confirmed group. Five cases in the confirmed group needed hospitalization. Two patients died while both of them were taking rituximab. The frequency rate of suspected cases with RRMS was 57 (87.7%), followed by 5 (7.7%) PPMS and 2 (3.1%) CIS. In the confirmed group, 25% used corticosteroid drug and 50% were on rituximab; moreover, 62.5% of the confirmed cases had a high disability level and needed assistance to walk. In whole, 36.8% of the suspected and 25% of the confirmed cases were on IFN-β1; eventually, all of them recovered well from COVID-19 infection.ConclusionIn the present study, the rate of developing COVID-19 in multiple sclerosis patients was similar to the general population and most of patients with multiple sclerosis recovered from COVID-19 without referral to a medical specialist.Keywords: COVID-19, Immunosuppressive, Multiple Sclerosis, General Population, Immunomodulatory therapy
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Chronic cerebral hypoperfusion (CCH) leads to vascular dementia with progressive hippocampal damage and cognitive impairments. In the present study, we compared early and late Minocycline (MINO) treatment on cognitive function, long and short-term synaptic-plasticity following CCH. We used bilateral common carotid arteries occlusion model (2VO) for induction of hypoperfusion. Male Sprague-Dawley rats were divided into 5 following groups (each having 2 subgroups): 2VO + V (vehicle), 2VO+MINO-E (early treatment of MINO on days 0 to 3 after 2VO), 2VO+MINO-L (late-treatment on days 21 to 32 after 2VO), control, and sham. Passive-avoidance (PA) and radial arm maze (RAM) tests were used to investigate learning and memory. Long term and short term synaptic plasticity were assessed by field potential recording, the brains were removed after recording and preserved for histological study to count pyramidal cells in CA1 region. Cerebral hypoperfusion could impair memory performance, synaptic plasticity, and basal synaptic transmission (BST) along with hippocampal cell loss. Thus, we found a significant reduction in step-through latency (STL) of PA test with a higher number of working and reference errors in RAM in CCH rats. However, only late treatment with MINO improved memory performance, synaptic plasticity, hippocampal cell loss, and increased neurotransmitter pool (NP) in CCH rats, but early treatment could not produce long-lasting beneficial effects 32 days after 2VO. MINO may improve synaptic plasticity and memory performance in hypo-perfused rats directly and indirectly by increasing NP and/or suppressing inflammatory factors, respectively.Keywords: chronic cerebral hypoperfusion, bilateral carotid occlusion, Minocycline, synaptic plasticity, Neurotransmitter release probability, basal synaptic transmission
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Neuro-Behcet's disease (NBD) is a rare but potentially fatal manifestation of Behcet's disease. Common presentations of neuro-Behcet's disease are parenchymal (brainstem manifestations, hemispheric manifestations, meningoencephalitis, spinal cord lesions) and non-parenchymal (arterial occlusions, aneurysms, Dural sinus thrombosis). Cerebrospinal fluid (CSF) findings in parenchymal NBD usually show an inflammatory pattern with elevated cell count (usually high levels of polymorphonuclear leukocytes), high protein, and normal glucose levels, whereas the CSF findings in non-parenchymal NBD could be normal except for high opening pressure. Further investigation of CSF in parenchymal NBD has demonstrated elevated Natural killer T cells, high inflammatory chemokines, and cytokines such as Tumor Necrosis Factor-alpha (TNF- α), Interferon-gamma (IFN-γ), Interleukin (IL)12, IL-6, IL-17, IL-26, IL-15, Vascular endothelial growth factor (VEGF), Matrix metallopeptidase 9 (MMP-9), chemokine [C-X-C motif] ligand 8 (CXC-8) which indicate the role of both innate and adaptive immunity in this disease. Particularly, T helper type 1 (TH-1) and TH-17pathways are implicated in the pathogenesis of this condition. Successful use of certain biologic agents such as the TNF inhibitors and IL-6 inhibitors in NBD further emphasizes the role of inflammatory cytokines in the immunopathogenesis of the disease. Drugs blocking the TH 17 pathway such as ustekinumab, secukinumab could also be applicable in the process. This review summarizes the detailed CSF findings in NBD, current understanding of the immunopathogenesis of NBD, and treatment of NBD with specific biologic agents based on our understanding of the disease pathogenesis.
Keywords: Behcet’s syndrome, Cerebrospinal Fluid, Neuro-Behcet’s Syndrome, Pathogenesis -
Objective(s)This study evaluated the impact of statin on the severity and outcome of stroke among patients who had taken it prior to the stroke onset and compared to patients who had not received it before the stroke.MethodsWe included 261 consecutive patients with acute ischemic stroke who admitted in Namazee hospital affiliated to Shiraz University of Medical Sciences from 2018-2019. We recorded demographic data, vascular risk factors, history of previous statin treatment, and National Institutes of Health Stroke Scale (NIHSS) score at time of hospital admission and modified Rankin Scale (MRS) 3 months after stroke onset. The dependent variables were initial severity of stroke as measured by National Institute of Health Scoring System (NIHSS) and good outcome defined as modified Rankin Scale (MRS) 0 to 1.ResultsAmong 261 patients with acute ischemic stroke, 76 were using statins (52.6% of users were women). Among all the subjects, 175 (67.6%) had history of hypertension, 78 (30.1%) had history of diabetes mellitus, 87(33.5%) had history of hyperlipidemia, 63 (24.3%) were smokers. Admission NIHSS and MRS were not statistically different in statin users and non-statin users (P= 0.12 and P= 0.08, respectively). Adjusted Odds Ratios for poor functional outcome and 90-day mortality according to previous statin use were 0.87 (95% CI 0.37-2.05), P= 0.54) and 0.75(95% CI 0.31-1.81, P= 0.52) which were not statistically significant.ConclusionThis study showed that pre-stroke statin therapy did not affect the initial clinical severity, short-term functional outcome and 90-day mortality after ischemic stroke.Keywords: Stroke, ischemic stroke, statin
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Background
There are limited data on vascular risk factors (VRFs) in low- and middle-income countries (LMICs). This meta-analysis was completed to summarize the existing evidence on stroke risk factors (SRFs) in the Iranian population.
MethodsAn electronic literature search of the databases including PubMed, Embase, Web of Science, Scopus, Scientific Information Database (SID), Magiran, and IranMedex was performed to identify the related articles published up to March 2018. For categorical or continuous variables, the data were also pooled using the fixed- or the random-effect models, respectively, expressed as odds ratio (OR) or weighted mean difference (WMD).
ResultsA total of 15 articles were recruited. The risk of stroke was associated with mean age, but not gender. Among traditional VRFs, hypertension (HTN), systolic and diastolic blood pressure (DBP), diabetes mellitus (DM), and fasting blood glucose (FBG) were associated with increased risk of stroke. Apart from the high circulating levels of triglycerides (TG), low-density lipoproteincholesterol (LDL-C), total cholesterol (TC), and low high-density lipoprotein-cholesterol (HDL-C), other potential risk factors namely cigarette smoking (CS), opioid addiction (OD), and waist circumference (WC) were identified to be independent stroke determinants.
ConclusionThe present systematic review and meta-analysis provided a summary of the most important SRFs, which are potentially modifiable and preventable. Overall, Iran, similar to many other LMICs, is experiencing an ever-increasing rate of stroke-prone elderly people. The LMICs are thus suggested to develop national approaches to recognize and address VRFs, to monitor and control CS and OD rates, and to encourage a healthy lifestyle.
Keywords: Iran, Low-, middle-income countries, Meta-analysis, Risk factor, Stroke -
Background
Neurological manifestations and complications are common in viral infections, and they are significant sources for clinical deterioration and poor clinical outcomes.
Case reportThe current report presents a 38year-old man with Covid-19 respiratory illness who subsequently developed neurological complications and clinical worsening leading to death. This patient sought medical attention after five days of progressive cough, fever, and dyspnea. On arrival in the emergency room, he was found to have hypoxic respiratory failure resulting in intubation and intensive care unit (ICU) admission. Chest CT scan was characteristic for Covid-19 infection, and PCR test on tracheal samples confirmed the diagnosis. On day nine of admission, he developed generalized tonic colonic seizure associated with deterioration of mental status and hemiparesis. Repeated brain CT scans showed subcortical hypoattenuation with associated sulcal effacement in the left occipital and posterior parietal lobes concerning for ischemic changes. The patient passed away on day 17 despite supportive measures.
Conclu-sionThis observation and recent evidence on Covid-19 CNS involvement highlight the need for further studies on early recognition of neurological complications in Covid-19 patients.
Keywords: Covid-19, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Brain, Stroke, Cerebrovascular Accident -
Background
Behçet's disease (BD) is a systemic inflammatory disease with a chronic, relapsing-remitting course of unknown etiology. Neuro-Behcet’s disease (NBD) induce serious CNS complications and are known to be the main cause of long-term morbidity and mortality. IL‐37 is a natural suppressor of innate inflammation which its role in NBD has not been fully understood.
ObjectiveTo determine the expression of IL-37 in cerebrospinal fluid (CSF) and its relationship with other inflammatory cytokines.
MethodsLevel of IL-37, IL-6, IL-17, IL-21, TSLP and TGF-β were measured in CSF of 22 patients with NBD and 12 non-inflammatory neurological disease (NIND) and 10 headache attributed to Behçet's disease (HaBD) by enzyme‐linked immunosorbent assay (ELISA). In addition, IL-37 mRNA relative expression was detected by quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR).
ResultsCSF level and mRNA expression of IL‐37 were elevated in NBD patients compared to those in NIND and HaBD patients. Levels of IL-6, IL-17, IL-21 and TSLP were found to be increased in NBD patients and were inversely associated with IL-37 level. Moreover, TGF-β level in CSF of NBD patients was positively correlated with IL-37 levels. IL-37 increased significantly after treatment and in remission group, but TGF-β was only increased in treatment group.
ConclusionIL‐37 expression increased in NBD patients, and correlated with disease activity. Our data conclude that IL-37 could be a disease marker in NBD, however it requires further studies.
Keywords: Interlukine-37, Inflammatory cytokines, Neuro-Behçet’s Disease -
Background
National Institute of Health Stroke Scale (NIHSS) and Modified National Institute of Health Stroke Scale (mNIHSS) are two valid and reliable questionnaires that assess stroke severity. This study aimed to examine and compare the validity and reliability of Persian versions of NIHSS and mNIHSS in hospitalized patients.
Materials and MethodsThe English versions of NIHSS and mNIHSS were translated to Persian (forward and backward), and three neurologists examined the face and content validity of both questionnaires. The Persian versions of NIHSS and mNIHSS were used in 75 hospitalized stroke patients (hemorrhagic and obstructive) admitted to Namazi teaching hospital, Shiraz, Iran. The reliability and validity of the Persian versions were examined by Cronbach’s alpha coefficient and convergent validity.
ResultsThe values of Cronbach’s alpha for Persian versions of NIHSS and mNIHSS were 0.81 and 0.86, respectively. The scaling success of convergent validity in NIHSS and mNIHSS were 80% and 100%, respectively.
ConclusionThe Persian versions of NIHSS and mNIHSS were reliable and valid. However, mNIHSS was more valid and reliable than NIHSS. Persian version of mNIHSS can be suggested to be used for assessing stroke severity in hospitalized stroke patients by neurologists and researchers.
Keywords: National Institute of Health Stroke Scale, Modified National Institute of Health Stroke Scale, Persian Version, Stroke
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