Magnetic hybrid nanovesicles for the precise diagnosis and treatment of central nervous system disorders.

INTRODUCTION: Central nervous system (CNS)-related disorders are increasingly being recognized as a global health challenge worldwide. There are significant challenges for effective diagnosis and treatment due to the presence of the CNS barriers which impede the management of neurological diseases. Combination of nanovesicles (NVs) and magnetic nanoparticles (MNPs), referred to as magnetic nanovesicles (MNVs), is now well suggested as a potential theranostic option for improving the management of neurological disorders with increased targeting efficiency and minimized side effects. AREAS COVERED: This review provides a summary of major CNS disorders and the physical barriers limiting the access of imaging/therapeutic agents to the CNS environment. A special focus on the unique features of MNPs and NV is discussed which make them attractive candidates for neuro-nanomedicine. Furthermore, a deeper understanding of MNVs as a promising combined strategy for diagnostic and/or therapeutic purposes in neurological disorders is provided. EXPERT OPINION: The multifunctionality of MNVs offers the ability to overcome the CNS barriers and can be used to monitor the effectiveness of treatment. The insights provided will guide future research toward better outcomes and facilitate the development of next-generation, innovative treatments for CNS disorders.

The efficacy and safety of interleukin-1 receptor antagonist in stroke patients: A systematic review.

Stroke is the leading cause of disability worldwide, yet there is currently no effective treatment available to mitigate its negative consequences. Pro-inflammatory cytokines, such as interleukin-1 (IL-1), are known to play a crucial role in exacerbating the aftermath of stroke. Thus, it is hypothesized that blocking inflammation and administering anti-inflammatory drugs at an optimal time and dosage may improve the long-term quality of life for stroke patients. This systematic review examines the effectiveness and safety of IL-1 receptor antagonist (IL-1Ra), commercially known as "anakinra," in clinical studies involving the treatment of stroke patients. A comprehensive literature search was conducted until October 2023 to identify relevant studies. The search yielded 1403 articles, out of which 598 were removed due to duplication. After a thorough review of 805 titles and abstracts, 797 articles were further excluded, resulting in 8 studies being included in this systematic review. The findings from all the included studies demonstrate that IL-1Ra is safe for use in acute ischemic and hemorrhagic stroke patients, with no significant adverse events reported. Additionally, biomarkers, clinical assessments, serious adverse events (AEs), and non-serious AEs consistently showed more favorable outcomes in IL-1Ra receiving patients. Stroke elevates the levels of several inflammatory cytokines, however, administration of IL-1RA directly or indirectly modulates these markers and improves some clinical outcomes, suggesting a potential therapeutic benefit of this intervention.

Do stroke services still show sex differences? A multicenter study.

BACKGROUND: The issue of sex differences in stroke has gained concern in the past few years. However, multicenter studies are still required in this field. This study explores sex variation in a large number of patients and compares stroke characteristics among women in different age groups and across different countries. METHODS: This multicenter retrospective cross-sectional study aimed to compare sexes regarding risk factors, stroke severity, quality of services, and stroke outcome. Moreover, conventional risk factors in women according to age groups and among different countries were studied. RESULTS: Eighteen thousand six hundred fifty-nine patients from 9 countries spanning 4 continents were studied. The number of women was significantly lower than men, with older age, more prevalence of AF, hypertension, and dyslipidemia. Ischemic stroke was more severe in women, with worse outcomes among women (p: < 0.0001), although the time to treatment was shorter. Bridging that was more frequent in women (p:0.002). Analyzing only women: ischemic stroke was more frequent among the older, while hemorrhage and TIA prevailed in the younger and stroke of undetermined etiology. Comparison between countries showed differences in age, risk factors, type of stroke, and management. CONCLUSION: We observed sex differences in risk factors, stroke severity, and outcome in our population. However, access to revascularization was in favor of women.

Nanoparticle Formulations of Antioxidants for the Management of Oxidative Stress in Stroke: A Review.

Stroke is currently one of the primary causes of morbidity and mortality worldwide. Unfortunately, there has been a lack of effective stroke treatment. Therefore, novel treatment strategies are needed to decrease stroke-induced morbidity and promote the patient's quality of life. Reactive oxygen species (ROS) have been recognized as one of the major causes of brain injury after ischemic stroke. Antioxidant therapy seems to be an effective treatment in the management of oxidative stress relevant to inflammatory disorders like stroke. However, the in vivo efficacy of traditional anti-oxidative substances is greatly limited due to their non-specific distribution and poor localization in the disease region. In recent years, antioxidant nanoparticles (NPs) have demonstrated a clinical breakthrough for stroke treatment. Some NPs have intrinsic antioxidant properties and act as antioxidants to scavenge ROS. Moreover, NPs provide protection to the antioxidant agents/enzymes while effectively delivering them into unreachable areas like the brain. Because of their nanoscale dimensions, NPs are able to efficiently pass through the BBB, and easily reach the damaged site. Here, we discuss the challenges, recent advances, and perspectives of antioxidant NPs in stroke treatment.

CNN-Res: deep learning framework for segmentation of acute ischemic stroke lesions on multimodal MRI images.

BACKGROUND: Accurate segmentation of stroke lesions on MRI images is very important for neurologists in the planning of post-stroke care. Segmentation helps clinicians to better diagnose and evaluation of any treatment risks. However, manual segmentation of brain lesions relies on the experience of neurologists and is also a very tedious and time-consuming process. So, in this study, we proposed a novel deep convolutional neural network (CNN-Res) that automatically performs the segmentation of ischemic stroke lesions from multimodal MRIs. METHODS: CNN-Res used a U-shaped structure, so the network has encryption and decryption paths. The residual units are embedded in the encoder path. In this model, to reduce gradient descent, the residual units were used, and to extract more complex information in images, multimodal MRI data were applied. In the link between the encryption and decryption subnets, the bottleneck strategy was used, which reduced the number of parameters and training time compared to similar research. RESULTS: CNN-Res was evaluated on two distinct datasets. First, it was examined on a dataset collected from the Neuroscience Center of Tabriz University of Medical Sciences, where the average Dice coefficient was equal to 85.43%. Then, to compare the efficiency and performance of the model with other similar works, CNN-Res was evaluated on the popular SPES 2015 competition dataset where the average Dice coefficient was 79.23%. CONCLUSION: This study presented a new and accurate method for the segmentation of MRI medical images using a deep convolutional neural network called CNN-Res, which directly predicts segment maps from raw input pixels.

Simultaneous Pericytes and M2 Microglia Transplantation Improve Cognitive Function in Mice Model of mPFC Ischemia.

Cerebral ischemia is one of the major problems threatening global health. Many of the cerebral ischemia survivors would suffer from the physical and cognitive disabilities for their whole lifetime. Cell based-therapies have been introduced as a therapeutic approach for alleviating ischemia-enforced limitations. Photothrombotic stroke model was applied on the left medial prefrontal cortex (mPFC) of adult male BALB/c mice. Then, pericytes isolated from brain microvessels of adult male BALB/c mice, microglia isolated from brain cortices of the neonatal male BALB/c mice, and M2 phenotype shifted microglia by IL-4 treatment were used for transplantation into the injured area after 24 h of ischemia induction. The behavioural outcomes evaluated by social interaction and Barnes tests and the levels of growth associated protein (GAP)-43 and inflammatory cytokine interleukin (IL)-1 protein were assessed by western blotting 7 days after cell transplantation. Animals in both of the microglia + pericytes and microglia M2 + pericytes transplanted groups showed better performance in social memory as well as enhanced spatial learning and memory compared to ischemic controls. Also, improved escape latency was only observed in microglia M2 + pericytes (p < 0.01) group compared to ischemic controls. GAP-43 showed significant protein expression in microglia + pericytes and microglia M2 + pericytes groups compared to the control group. Conversely, IL-1 levels diminished in all of the pericytes microglia + pericytes, and microglia M2 + pericytes groups compared to the ischemic controls. Current study highlights efficiency of M2 microglia and pericytes combinatory transplantation therapeutic role on relieving ischemic stroke outcomes.

Tau Protein Biosensors in the Diagnosis of Neurodegenerative Diseases.

Tau protein plays a crucial role in diagnosing neurodegenerative diseases. However, performing an assay to detect tau protein on a nanoscale is a great challenge for early diagnosis of diseases. Enzyme-linked immunosorbent assay (ELISA), western-blotting, and molecular-based methods, e.g., PCR and real-time PCR, are the most widely used methods for detecting tau protein. These methods are subject to certain limitations: the need for advanced equipment, low sensitivity, and specificity, to name a few. With the above said, it is necessary to discover advanced and novel methods for monitoring tau protein. Counted among remarkable approaches adopted by researchers, biosensors can largely eliminate the difficulties and limitations associated with conventional methods. The main objective of the present study is to review the latest biosensors developed to detect the tau protein. Furthermore, the problems and limitations of conventional diagnosis methods were discussed in detail.

Stroke services in MENA: What is there and what is needed.

OBJECTIVES: Stroke represents a health care challenge to most parts of the world including the Middle East and North Africa (MENA) region. The MENA represents 6% of the world population with an age-standardized stroke rate of 87.7 (78.2-97.6) per 100,000 population. This number is subject to increase given that the cause of morbidity has recently shifted from infectious diseases to non-communicable diseases. Thus, in the coming years, treatment of stroke will pose a major burden on MENA countries which mostly lie in the low to middle income economies. Accordingly, we need to study the state of MENA stroke services in order to recognize and further inform policy makers about any gaps that need to be bridged in this domain. METHODS AND RESULTS: Stroke specialists representing 16 countries filled an online survey that included: screening for risk factors, acute management, diagnostics, medications, post-discharge services, and stroke registries. Results showed that 11 countries screen for risk factors, 16 have neuroimaging studies, 15 provide intravenous thrombolysis (IVT), 13 mechanical thrombectomy (MT) while medications for secondary prevention are available in all countries. However, stroke units are not equally available and even absent in 4 countries, and despite the availability of IVT yet, the rate of administration is still low in 6 countries (<5%), and ranges from 5-20% in 7 countries. Stroke registries and training still need to be implemented in most countries. CONCLUSION: Although imaging, revascularization therapies and medications for secondary prevention are available in most MENA countries, yet the rate of revascularization is low, so is the number of stroke units insufficient in some countries. Additionally, registries and structured training are still defective. Further field studies are required for more accurate determination of the status of stroke services in the MENA region.

Efficacy and safety of decompressive craniectomy in acute ischemic stroke patients treated with intravenous thrombolysis.

INTRODUCTION: The optimal timing for decompressive hemicraniectomy (DHC) after intravenous thrombolysis (IVT) remains unclear. This study in patients with acute ischemic stroke treated with IVT aimed to assess the safety of DHC and patient outcome. METHODS: Data was extracted from the Tabriz stroke registry from June 2011 up to September 2020. In all, 881 patients were treated with IVT. Among these, 23 patients underwent DH. Six patients were excluded due to symptomatic intracranial hemorrhage (parenchymal hematoma type 2 based on SITS-MOST definition) after IVT, but other types of bleeding after venous thrombolysis, including HI1, HI2, and PH1 were not excluded; so the remaining 17 patients were enrolled in the study. Functional Outcome was defined as the proportion of patients who achieved mRS score of 2-3 (moderate disability), 4-5 (severe disability), or 6 (mortality) at 90 days after stroke. mRSwas assess by trained neurologist at the hospital clinic with direct interview Safety outcome was assessed by comparison of two scans just prior to and after craniectomy. Any new hemorrhage or worsening of previous hemorrhage was reported. Parenchymal hematoma type 2, based on ECASS II definition, was considered as major surgical complication. This study was approved by the local ethics committee of the Tabriz University of Medical Sciences (Ethics Code: IR.TBZMED.REC.1398.420). RESULTS: At the three-month mRS follow up, six patients (35%) had moderate and five (29%) had severe disability. The outcome of death was observed in six patients (35%).Nine of 15 patients (60%) underwent surgery in the first 48 hours after onset of symptoms. No patient over 60 years of age survived to the three-month follow up; 67% of those who were under60 years and underwent DH in the first 48 hours had favorable outcome. Hemorrhagic complication was seen in 64% of patients but none was major. CONCLUSION: Results of this study showed that the rate of major bleeding and outcome of acute ischemic stroke patients who underwent DHC after IVT is comparable with the reported data in the literature and intentionally waiting for the fibrinolytic effects of IVT to disappear may not outweigh the benefits of DHC. Although the findings of the study should be interpreted with caution and larger studies are needed to confirm the results.

Cellular, histological, and behavioral pathological alterations associated with the mouse model of photothrombotic ischemic stroke.

BACKGROUND: Photothrombotic (PT) stroke model is a reliable method to induce ischemic stroke in the target site using the excitation of photosensitive agents such as Rose Bengal (RB) dye after light illumination. Here, we performed a PT-induced brain ischemic model using a green laser and photosensitive agent RB and confirmed its efficiency through cellular, histological, and neurobehavioral approaches. METHODS: Mice were randomly allocated into RB; Laser irradiation; and RB + Laser irradiation groups. Mice were exposed to a green laser at a wavelength of 532 nm and intensity of 150 mW in a mouse model after injection of RB under stereotactic surgery. The pattern of Hemorrhagic and ischemic changes were evaluated throughout the study. The volume of the lesion site was calculated using unbiased stereological methods. For investigation of neurogenesis, we performed double - (BrdU/NeuN) immunofluorescence (IF) staining on day 28 following the last- BrdU injection. To assess the effect and quality of ischemic stroke on neurological behavior, the Modified neurological severity score (mNSS) test was done on days 1, 7, 14, and 28 days after stroke induction. RESULTS: Laser irradiation plus RB induced hemorrhagic tissue and pale ischemic changes over the 5 days. In the next few days, microscopic staining revealed neural tissue degeneration, demarcated necrotic site, and neuronal injury. BrdU staining showed a significant number of proliferating cells in the periphery of the lesion site in the Laser irradiation plus RB group compared to the group (p < 0.05) while the percent of NeuN+ cells per BrdU- positive cells was reduced. Also, prominent astrogliosis was observed in the periphery of irradiated sites on day 28. Neurological deficits were detected in mice from Laser irradiation plus the RB group. No histological or functional deficits were detected in RB and Laser irradiation groups. CONCLUSIONS: Taken together, our study showed cellular and histologic pathological changes which are associated with the PT induction model. Our findings indicated that the undesirable microenvironment and inflammatory conditions could affect neurogenesis concomitantly with functional deficits. Moreover, this research showed that this model is a focal, reproducible, noninvasive and accessible stroke model with a distinctive demarcation similar to human stroke conditions.

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.

Nanoparticle and Stem Cell Combination Therapy for the Management of Stroke.

Stroke is currently one of the primary causes of morbidity and mortality worldwide. Unfortunately, the available treatments for stroke are still extremely limited. Indeed, stem cell (SC) therapy is a new option for the treatment of stroke that could significantly expand the therapeutic time window of stroke. Some proposed mechanisms for stroke-based SC therapy are the incorporation of SCs into the host brain to replace dead or damaged cells/tissues. Moreover, acute cell delivery can inhibit apoptosis and decrease lesion size, providing immunomudolatory and neuroprotection effects. However, several major SC problems related to SCs such as homing, viability, uncontrolled differentiation, and possible immune response, have limited SC therapy. A combination of SC therapy with nanoparticles (NPs) can be a solution to address these challenges. NPs have received considerable attention in regulating and controlling the behavior of SCs because of their unique physicochemical properties. By reviewing the pathophysiology of stroke and the therapeutic benefits of SCs and NPs, we hypothesize that combined therapy will offer a promising future in the field of stroke management. In this work, we discuss recent literature in SC research combined with NP-based strategies that may have a synergistic outcome after stroke incidence.

SARS-CoV-2 infection might be a predictor of mortality in intracerebral hemorrhage.

BACKGROUND: SARS-CoV-2 infection may be associated with uncommon complications such as intracerebral hemorrhage (ICH), with a high mortality rate. We compared a series of hospitalized ICH cases infected with SARS-CoV-2 with a non-SARS-CoV-2 infected control group and evaluated if the SARS-CoV-2 infection is a predictor of mortality in ICH patients. METHODS: In a multinational retrospective study, 63 cases of ICH in SARS-CoV-2 infected patients admitted to 13 tertiary centers from the beginning of the pandemic were collected. We compared the clinical and radiological characteristics and in-hospital mortality of these patients with a control group of non-SARS-CoV-2 infected ICH patients of a previous cohort from the country where the majority of cases were recruited. RESULTS: Among 63 ICH patients with SARS-CoV-2 infection, 23 (36.5%) were women. Compared to the non-SARS-CoV-2 infected control group, in SARS-CoV-2 infected patients, ICH occurred at a younger age (61.4 ± 18.1 years versus 66.8 ± 16.2 years, P = 0.044). These patients had higher median ICH scores ([3 (IQR 2-4)] versus [2 (IQR 1-3)], P = 0.025), a more frequent history of diabetes (34% versus 16%, P = 0.007), and lower platelet counts (177.8 ± 77.8 × 109/L versus 240.5 ± 79.3 × 109/L, P < 0.001). The in-hospital mortality was not significantly different between cases and controls (65% versus 62%, P = 0.658) in univariate analysis; however, SARS-CoV-2 infection was significantly associated with in-hospital mortality (aOR = 4.3, 95% CI: 1.28-14.52) in multivariable analysis adjusting for potential confounders. CONCLUSION: Infection with SARS-CoV-2 may be associated with increased odds of in-hospital mortality in ICH patients.

Effect of music on driving performance and physiological and psychological indicators: A systematic review and meta-analysis study.

Background: Many studies have assessed the effect of music on driving. However, their results are very scattered and contradictory. Therefore, this systematic review is conducted to determine the effect of music on driving performance and drivers' physiological and psychological indicators. Methods: Scopus, PubMed, and Web of Science databases were searched until July 2023. A manual search in Google Scholar for gray literature was conducted. The Simulation Research Rubric (SRR) tool was used to assess the reporting quality of the studies. Stata software (StataCorp, version 16) was used to perform a meta-analysis. Results: A total of 2650 records were identified. The findings of 19 studies were analyzed. Most of them were carried out in high-income countries (HICs) using simulators. The most frequently used music style was classic rock. The meta-analysis results indicated that music with high and medium volume increases the average driving speed, and music with low volume decreases it. Although music in every mood reduces the average reaction time, it positively reduces response delay and increases coherence. Music with high volume decreases the heart rate, but music with medium and low volume increases it. Listening to music increases the level of arousal and mental load. Conclusion: It was concluded that, in some indicators, listening to music has adverse effects on driving. However, in many indicators, music has a positive impact on improving driving safety. It is better to choose appropriate music for different driving conditions and to train the drivers about it.

Working memory assessment using cambridge neuropsychological test automated battery can help in the diagnosis of mild cognitive impairment: a systematic review and meta-analysis.

Mild cognitive impairment (MCI) is an interstitial state between normal aging and dementia. Objective: In this study, we investigated working memory (WM) profiles of MCI patients using the Cambridge Neuropsychological Test Automated Battery (CANTAB). We also examined the diagnostic accuracy and possible associated factors as secondary outcomes of the study. Methods: We conducted an electronic search on EMBASE, PubMed, and ScienceDirect databases. Studies with MCI participants and using CANTAB battery subtests for the assessment of WM were included. Meta-analysis was conducted using the CMA2 software. Results: Out of 1537 records, 14 studies were covered in this systematic review, and 7 of them were included in the meta-analysis. There was a significant difference between MCI patients and healthy controls in spatial working memory (SWM) (SDM: 0.535; 95%CI 11-96; p-value=0.014), spatial span (SSP) (SDM: 0.649 95%CI 0.297-0.100; p-value<0.01), and rapid visual information processing (RVP) (SDM: 0.52; 95%CI 0.386-0.654; p-value<0.01). WM function of MCI patients was associated with the cerebrospinal fluid (CSF) levels of tau-protein and amyloid-beta (Aß). Conclusions: WM is an impaired cognitive domain in MCI. CANTAB WM subtests including SSP, SWM, and RVP are accurate enough to be used as a proper assessment tool for the diagnosis of MCI in clinical settings. Tau-protein and Aß are associated with lower WM scores in MCI patients; however, sex, age, psychiatric disorders, apolipoprotein 4 allele, and functional activity scores cannot affect WM.

O comprometimento cognitivo leve (CCL) é um estado intersticial entre o envelhecimento normal e a demência. Objetivo: Neste estudo, investigamos os perfis de memória de trabalho (MT) de pacientes com CCL usando a bateria automatizada de testes neuropsicológicos de Cambridge (Cambridge Neuropsychological Test Automated Battery ­ CANTAB). Também examinamos a acurácia diagnóstica e possíveis fatores associados como desfechos secundários do estudo. Métodos: Foi realizada uma busca eletrônica nas bases de dados EMBASE, PubMed e ScienceDirect. Foram incluídos estudos com participantes com CCL e utilizando subtestes da bateria CANTAB para avaliação da MT. A meta-análise foi realizada usando o software CMA2. Resultados: Dos 1.537 registros, esta revisão sistemática abordou 14 estudos, e 7 deles foram incluídos na meta-análise. Houve uma diferença significativa entre pacientes com CCL e controles saudáveis na memória de trabalho espacial (MTE) (DPM: 0,535; IC95% 11­96; valor p=0,014), spatial span (SSP) (SDM: 0,649; IC95% 0,297­0,100; valor p<0,01) e processamento rápido de informação visual (PRV) (DPM: 0,52; IC95% 0,386­0,654; valor p<0,01). A MT de pacientes com CCL foi associada com os níveis de proteína tau e beta-amiloide (Aß) no líquido cefalorraquidiano (CSF). Conclusões: A MT é um domínio cognitivo prejudicado no CCL. Os subtestes CANTAB WM, incluindo SSP, MTE e PRV, são precisos o suficiente para serem usados como uma ferramenta de avaliação adequada para o diagnóstico de CCL em ambientes clínicos. A proteína Tau e Aß estão associadas a pontuações de MT mais baixas em pacientes com CCL; entretanto, sexo, idade, transtornos psiquiátricos, alelo da apolipoproteína 4 e escores de atividade funcional não podem afetar a MT.

Working memory assessment using cambridge neuropsychological test automated battery can help in the diagnosis of mild cognitive impairment: a systematic review and meta-analysis / A avaliação da memória de trabalho usando a bateria automatizada do cambridge neuropsychological test pode ajudar no diagnóstico de comprometimento cognitivo leve: uma revisão sistemática e meta-análise

ABSTRACT Mild cognitive impairment (MCI) is an interstitial state between normal aging and dementia. Objective: In this study, we investigated working memory (WM) profiles of MCI patients using the Cambridge Neuropsychological Test Automated Battery (CANTAB). We also examined the diagnostic accuracy and possible associated factors as secondary outcomes of the study. Methods: We conducted an electronic search on EMBASE, PubMed, and ScienceDirect databases. Studies with MCI participants and using CANTAB battery subtests for the assessment of WM were included. Meta-analysis was conducted using the CMA2 software. Results: Out of 1537 records, 14 studies were covered in this systematic review, and 7 of them were included in the meta-analysis. There was a significant difference between MCI patients and healthy controls in spatial working memory (SWM) (SDM: 0.535; 95%CI 11-96; p-value=0.014), spatial span (SSP) (SDM: 0.649 95%CI 0.297-0.100; p-value<0.01), and rapid visual information processing (RVP) (SDM: 0.52; 95%CI 0.386-0.654; p-value<0.01). WM function of MCI patients was associated with the cerebrospinal fluid (CSF) levels of tau-protein and amyloid-beta (Aβ). Conclusions: WM is an impaired cognitive domain in MCI. CANTAB WM subtests including SSP, SWM, and RVP are accurate enough to be used as a proper assessment tool for the diagnosis of MCI in clinical settings. Tau-protein and Aβ are associated with lower WM scores in MCI patients; however, sex, age, psychiatric disorders, apolipoprotein 4 allele, and functional activity scores cannot affect WM.

RESUMO O comprometimento cognitivo leve (CCL) é um estado intersticial entre o envelhecimento normal e a demência. Objetivo: Neste estudo, investigamos os perfis de memória de trabalho (MT) de pacientes com CCL usando a bateria automatizada de testes neuropsicológicos de Cambridge (Cambridge Neuropsychological Test Automated Battery - CANTAB). Também examinamos a acurácia diagnóstica e possíveis fatores associados como desfechos secundários do estudo. Métodos: Foi realizada uma busca eletrônica nas bases de dados EMBASE, PubMed e ScienceDirect. Foram incluídos estudos com participantes com CCL e utilizando subtestes da bateria CANTAB para avaliação da MT. A meta-análise foi realizada usando o software CMA2. Resultados: Dos 1.537 registros, esta revisão sistemática abordou 14 estudos, e 7 deles foram incluídos na meta-análise. Houve uma diferença significativa entre pacientes com CCL e controles saudáveis na memória de trabalho espacial (MTE) (DPM: 0,535; IC95% 11-96; valor p=0,014), spatial span (SSP) (SDM: 0,649; IC95% 0,297-0,100; valor p<0,01) e processamento rápido de informação visual (PRV) (DPM: 0,52; IC95% 0,386-0,654; valor p<0,01). A MT de pacientes com CCL foi associada com os níveis de proteína tau e beta-amiloide (Aβ) no líquido cefalorraquidiano (CSF). Conclusões: A MT é um domínio cognitivo prejudicado no CCL. Os subtestes CANTAB WM, incluindo SSP, MTE e PRV, são precisos o suficiente para serem usados como uma ferramenta de avaliação adequada para o diagnóstico de CCL em ambientes clínicos. A proteína Tau e Aβ estão associadas a pontuações de MT mais baixas em pacientes com CCL; entretanto, sexo, idade, transtornos psiquiátricos, alelo da apolipoproteína 4 e escores de atividade funcional não podem afetar a MT.

The Link between Stroke Risk and Orodental Status-A Comprehensive Review.

One of the primary causes of disability and mortality in the adult population worldwide is stroke. A person's general health is significantly impacted by their oral and dental health. People who have poor oral health are more susceptible to conditions such as stroke. Stroke risk has long been linked to oral and dental conditions. The risk of stroke and its cost impact on the healthcare systems appear to be significantly reduced as a result of the decline in the incidence and prevalence of oral and dental illnesses. Hypothetically, better management of oral hygiene and dental health lead to reduced stroke risk. To the authors' best knowledge, for the first time, the potential link between dental health and stroke were cross-examined. The most typical stroke symptoms, oral and dental illnesses linked to stroke, and the role of oral healthcare professionals in stroke prevention are revealed. The potential mediating processes and subsequent long-term cognitive and functional neurological outcomes are based on the available literature. It must be noted that periodontal diseases and tooth loss are two common oral health measures. Lack of knowledge on the effects of poor oral health on systemic health together with limited access to primary medical or dental care are considered to be partially responsible for the elevated risk of stroke. Concrete evidence confirming the associations between oral inflammatory conditions and stroke in large cohort prospective studies, stratifying association between oral disease severity and stroke risk and disease effects on stroke survival will be desirable. In terms of clinical pathology, a predictive model of stroke as a function of oral health status, and biomarkers of systemic inflammation could be useful for both cardiologists and dentists.

Effect of intranasal administration of caffeine on mPFC ischemia­induced cognitive impairment in BALB/c mice.

Caffeine is a psychoactive compound used widely to enhance cognitive functions in human or animal studies. The present study examined the effects of caffeine on cognitive performance and inflammatory factors in mice with medial prefrontal cortex (mPFC) ischemia. Mice underwent a photothrombotic mPFC ischemic stroke and were treated with normal saline or caffeine at different doses intranasally for 7 days. The sham surgery animals received normal saline intranasally. The Morris water maze test and social interaction test were performed to assess spatial and social memories, respectively. In addition, the levels of inflammatory proteins, including tumor necrosis factor­alpha, interleukin­6, and interleukin­10, were measured in the mPFC using immunoblotting. The results showed that mPFC ischemia impaired spatial memory and social behaviors, and caffeine at doses of 0.05 and 0.1 mg improved behavioral outcomes in the ischemic groups. Also, caffeine reversed ischemia­induced high levels of pro­inflammatory biomarkers and enhanced the expression of the anti­inflammatory mediator. Our findings indicate that caffeine alleviated mPFC ischemia­induced memory disturbances, probably through the modulation of the inflammatory mediators.

Intranasal administration of mitochondria alleviated cognitive impairments and mitochondrial dysfunction in the photothrombotic model of mPFC stroke in mice.

OBJECTIVES: Dysfunction in mitochondrial activity may have profound role in ischemic stroke-induced neuronal death, hence maintaining the mitochondrial function seems to be valuable for neuronal viability and neurological improvement. METHODS: C57BL/6J mice were allocated into sham and stroke groups. Mice in the stroke groups underwent photothrombosis-induced stroke in the medial prefrontal cortex (mPFC) and were divided into the following subgroups; RB, Mito 85, Mito 170, and Mito 340, and received their respective treatments via intra-nasal route every other day (3 days per week) for one week. A battery of behavioral tests including social interaction, passive avoidance, and the Lashley III maze was used to investigate social, contextual, and spatial memories. Moreover, changes in mitochondrial function, including reactive oxygen species (ROS) and ATP levels, and mitochondrial membrane potential, were assessed in mPFC. The expression of growth-associated protein 43 (GAP-43), post-synaptic density-95 (PSD-95), and synaptophysin (SYP) was detected by western blotting. RESULTS: Behavioral results revealed that mitotherapy alleviated ischemia-induced memory impairment. Also, transplantation of exogenous mitochondria lowered ROS, restored ATP generation, and improved mitochondrial membrane potential. Induction of ischemia decreased the levels of synaptic markers in mPFC while exogenous mitochondria (170 and 340µg) significantly upregulated the expression of GAP-43 and PSD-95 after ischemic stroke. CONCLUSION: Our research highlighted the importance of mitotherapy in regulating synaptic markers expression and mitochondria function, which could represent a potential strategy for improving cognitive and memory deficits following stroke.

Psychometric properties of the Persian version of neurogenic bladder symptom score questionnaire: A methodological study on patients with multiple sclerosis and stroke.

OBJECTIVES: Concerning the impact of neurogenic lower urinary tract dysfunction (NLUTD) on quality of life, besides the lack of standard psychometrically-analyzed Persian tools, the present study investigated the validity and reliability of the Persian version of the neurogenic bladder symptom score (NBSS) questionnaire. METHODS: A total of 279 multiple sclerosis (MS) or stroke/cerebrovascular accident (CVA) patients over 18 years of age with NLUTD referred to the neurology clinics entered the study in 2021-2022. After translation, back-translation, and developing a Persian version, its validity and reliability were determined. The content validity index (CVI) and content validity ratio (CVR) were calculated quantitatively. To determine the internal consistency and scale reliability, a test-retest was used. RESULTS: The Cronbach's α coefficient was 0.83 and the intraclass correlation coefficient (95% confidence interval) was 0.85 (0.82, 0.88). Cronbach's α in all domains (incontinence, storage and voiding, and consequence) was greater than 0.70. The criterion validity also showed a positive correlation of NBSS with the International Consultation on Incontinence Questionnaire-overactive bladder (p < 0.001 and r = 0.55). The face validity was acceptable according to the opinion of 10 participants. To determine the CVI and the CVR, 10 experts' panels reviewed all items related to the questionnaire in terms of necessity, clarity, transparency, and relevancy. Based on the expert panel all NBSS criteria got a high score, and all criteria were essential to assess NLUTD (CVI: 0.78-1). CONCLUSIONS: Regarding validity and reliability, the Persian version NBSS questionnaire can properly evaluate NLUTD in MS or stroke/CVA patients.