Insulin-like growth factor-1 (IGF-1) levels in multiple sclerosis patients: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Multiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon degeneration. Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide mainly synthesized in the liver and brain. IGF-1 causes neuronal and non-neuronal cell proliferation, survival, and differentiation. Therefore, it can be used in treating neuro-demyelinating diseases such as MS. The current systematic review and meta-analysis aims to compare the levels of IGF-1 in MS patients and healthy controls and also investigates IGF binding proteins (IGF-BP) and growth hormone (GH) levels between MS patients and healthy controls. METHODS: In this study, we systematically searched electronic databases of PubMed, Scopus, Web of Science (WOS), and Google Scholar, up to December 2022. Studies that measured IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and healthy controls in either blood or cerebral spinal fluid (CSF) were identified. We calculated Standardized mean differences (SMD) to compare levels of IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and controls. RESULTS: Finally, we included 11 eligible studies from 1998 to 2018. The sample size of included studies varied from 20 to 200 resulting in a total sample size of 1067 individuals, 531 MS patients, and 536 healthy controls. The mean age of the patient and control groups were 38.96 and 39.38, respectively. The average EDSS among patients was 4.56. We found that blood levels of IGF-1 (SMD = 0.20, 95% CI = -0.20 to 0.59, I2 = 82.4%, K = 8, n = 692), CSF level of IGF-1 (SMD = 0.25, 95% CI = -0.06 to 0.56, I2 = 0.0%, K = 3 n = 164) and blood levels of GH were not significantly higher in MS patients than controls (SMD = 0.08, 95% CI = -0.33 to 0.49, I2 = 77.0% K = 3, n = 421). Moreover, the blood levels of IGFBP-1 (SMD = 0.70, 95% CI = 0.01 to 1.40, I2 = 77%, K = 4, n = 255) were significantly higher in MS cases than in controls. However, the blood levels of IGFBP-2 (SMD = 0.43, 95% CI = -0.34 to 1.21, I2 = 64.2%, K = 3, n = 78) and blood levels of IGFBP-3 (SMD = 1.04, 95% CI = -0.09 to 2.17, I2 = 95.6%, K = 6, n = 443) were not significantly higher in patients than controls. CONCLUSION: Our meta-analysis revealed no significant difference in serum levels of IGF-1, GH, IGFBP-2, and IGFBP-3 between the MS group and healthy controls, except for IGFBP1. However, our systematic review showed that the studies were controversial for IGFBP-3 serum levels. Some studies found an increase in serum level of IGFBP-3 in MS patients compared to the healthy group, while others showed a decrease.

Iron quantification in basal ganglia: quantitative susceptibility mapping as a potential biomarker for Alzheimer's disease - a systematic review and meta-analysis.

Introduction: Alzheimer's disease (AD), characterized by distinctive pathologies such as amyloid-ß plaques and tau tangles, also involves deregulation of iron homeostasis, which may accelerate neurodegeneration. This meta-analysis evaluated the use of quantitative susceptibility mapping (QSM) to detect iron accumulation in the deep gray matter (DGM) of the basal ganglia in AD, contributing to a better understanding of AD progression, and potentially leading to new diagnostic and therapeutic approaches. Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched the PubMed, Scopus, Web of Sciences, and Google Scholar databases up to October 2023 for studies employing QSM in AD research. Eligibility criteria were based on the PECO framework, and we included studies assessing alterations in magnetic susceptibility indicative of iron accumulation in the DGM of patients with AD. After initial screening and quality assessment using the Newcastle-Ottawa Scale, a meta-analysis was conducted to compare iron levels between patients with AD and healthy controls (HCs) using a random-effects model. Results: The meta-analysis included nine studies comprising 267 patients with AD and 272 HCs. There were significantly higher QSM values, indicating greater iron deposition, in the putamen (standardized mean difference (SMD) = 1.23; 95% CI: 0.62 to 1.84; p = 0.00), globus pallidus (SMD = 0.79; 95% CI: 0.07 to 1.52; p = 0.03), and caudate nucleus (SMD = 0.72; 95% CI: 0.39 to 1.06; p = 0.00) of AD patients compared to HCs. However, no significant differences were found in the thalamus (SMD = 1.00; 95% CI: -0.42 to 2.43; p = 0.17). The sensitivity analysis indicated that no single study impacted the overall results. Age was identified as a major contributor to heterogeneity across all basal ganglia nuclei in subgroup analysis. Older age (>69 years) and lower male percentage (≤30%) were associated with greater putamen iron increase in patients with AD. Conclusion: The study suggests that excessive iron deposition is linked to the basal ganglia in AD, especially the putamen. The study underscores the complex nature of AD pathology and the accumulation of iron, influenced by age, sex, and regional differences, necessitating further research for a comprehensive understanding.

Machine Learning Approaches to Identify Affected Brain Regions in Movement Disorders Using MRI Data: A Systematic Review and Diagnostic Meta-analysis.

BACKGROUND: Movement disorders such as Parkinson's disease are associated with structural and functional changes in specific brain regions. Advanced magnetic resonance imaging (MRI) techniques combined with machine learning (ML) are promising tools for identifying imaging biomarkers and patterns associated with these disorders. PURPOSE/HYPOTHESIS: We aimed to systematically identify the brain regions most commonly affected in movement disorders using ML approaches applied to structural and functional MRI data. We searched the PubMed and Scopus databases using relevant keywords up to June 2023 for studies that used ML approaches to detect brain regions associated with movement disorders using MRI data. STUDY TYPE: A systematic review and diagnostic meta-analysis. POPULATION/SUBJECTS: Sixty-seven studies with 6,285 patients were included. FIELD STRENGTH/SEQUENCE: Studies utilizing 1.5T or 3T MR scanners and the acquisition of diffusion tensor imaging (DTI), structural MRI (sMRI), functional MRI (fMRI), or a combination of these were included. ASSESSMENT: The authors independently assessed the study quality using the CLAIM and QUADAS-2 criteria and extracted data on diagnostic accuracy measures. STATISTICAL TESTS: Sensitivity, specificity, accuracy, and area under the curve were pooled using random-effects models. Q statistics and the I2 index were used to evaluate heterogeneity, and Begg's funnel plot was used to identify publication bias. RESULTS: sMRI showed the highest sensitivity (93%) and mixed modalities had the highest specificity (90%) for detecting regional abnormalities. sMRI had a 94% sensitivity for identifying subcortical changes. The support vector machine (93%) and logistic regression (91%) models exhibited high diagnostic accuracies. DATA CONCLUSION: The combination of advanced MR neuroimaging techniques and ML is a promising approach for identifying brain biomarkers and affected regions in movement disorders with subcortical structures frequently implicated. Structural MRI, in particular, showed strong performance. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Quantitative susceptibility mapping for iron monitoring of multiple subcortical nuclei in type 2 diabetes mellitus: a systematic review and meta-analysis.

Introduction: Iron accumulation in the brain has been linked to diabetes, but its role in subcortical structures involved in motor and cognitive functions remains unclear. Quantitative susceptibility mapping (QSM) allows the non-invasive quantification of iron deposition in the brain. This systematic review and meta-analysis examined magnetic susceptibility measured by QSM in the subcortical nuclei of patients with type 2 diabetes mellitus (T2DM) compared with controls. Methods: PubMed, Scopus, and Web of Science databases were systematically searched [following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines] for studies reporting QSM values in the deep gray matter (DGM) regions of patients with T2DM and controls. Pooled standardized mean differences (SMDs) for susceptibility were calculated using fixed-effects meta-analysis models, and heterogeneity was assessed using I2. Sensitivity analyses were conducted, and publication bias was evaluated using Begg's and Egger's tests. Results: Six studies including 192 patients with T2DM and 245 controls were included. This study found a significant increase in iron deposition in the subcortical nuclei of patients with T2DM compared to the control group. The study found moderate increases in the putamen (SMD = 0.53, 95% CI 0.33 to 0.72, p = 0.00) and dentate nucleus (SMD = 0.56, 95% CI 0.27 to 0.85, p = 0.00) but weak associations between increased iron levels in the caudate nucleus (SMD = 0.32, 95% CI 0.13 to 0.52, p = 0.00) and red nucleus (SMD = 0.22, 95% CI 0.00 0.44, p = 0.05). No statistical significance was found for iron deposition alterations in the globus pallidus (SMD = 0.19; 95% CI -0.01 to 0.38; p = 0.06) and substantia nigra (SMD = 0.12, 95% CI -0.10, 0.34, p = 0.29). Sensitivity analysis showed that the findings remained unaffected by individual studies, and consistent increases were observed in multiple subcortical areas. Discussion: QSM revealed an increase in iron in the DGM/subcortical nuclei in T2DM patients versus controls, particularly in the motor and cognitive nuclei, including the putamen, dentate nucleus, caudate nucleus, and red nucleus. Thus, QSM may serve as a potential biomarker for iron accumulation in T2DM patients. However, further research is needed to validate these findings.

Possible cognition changes in women with polycystic ovary syndrome: a narrative review.

Nowadays, polycystic ovary syndrome (PCOS) and cognitive dysfunction are major health problems among female. This narrative review aimed to investigate cognitive dysfunction in female with PCOS. English and Persian articles published in PubMed, Scopus, Web of Science, Google Scholar, PsycINFO, Scientific Information Database, and Cochrane Database of Systematic Reviews until May 2022 were searched. Sixteen studies involving 850 female with PCOS and 974 controls were assessed. In these studies, the association between biochemical factors and symptoms of PCOS and memory, attention, executive functioning, information processing speed, and visuospatial skills was evaluated. The literature review revealed the possible cognitive changes in female with PCOS. This study summarized the different aspects of cognitive function in female with PCOS due to medication, psychological problems (mood disorders caused by disease symptoms and complications), and biochemical markers, such as metabolic and sex hormone abnormalities. Considering the existing scientific gap regarding the possibility of cognitive complications in female with PCOS, further biological studies should be conducted to evaluate the potential mechanisms involved.

Endocannabinoid system as a therapeutic target for psychostimulants relapse: A systematic review of preclinical studies.

The mechanism behind the reinstament of psychostimulant, as a major obstacle in addiction treatment is not fully understood. Controversial data are available in the literature concerning the role of the endocannabinoid (eCB) system in regulating the relapse to psychostimulant addiction in preclinical studies. The current systematic review aims to evaluate eCB modulators' effect in the reinstatement of commonly abused psychostimulants, including cocaine, amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine. By searching the PubMed, Web of Science, and Scopus databases, studies were selected. Then the studies, quality was evaluated by the SYRCLE risk of bias tool. The results have still been limited to preclinical studies. Thirty-nine articles that employed self-administration and CPP as the most prevalent animal models of addiction were selected. This data indicates that cannabinoid receptor 1 antagonists and some cannabinoid receptor 2 agonists could suppress the reinstatement of cocaine and methamphetamine addiction in a dose-dependent manner. However, only AM251 was efficient to block the reinstatement of 3,4-methylenedioxymethamphetamine. In conclusion, cannabinoid receptor 1 antagonists and some cannabinoid receptor 2 agonists may have curative potential in the relapse of psychostimulant abuse. However, time, dose, and route of administration are crucial factors in their inhibitory impacts.

Role of amyloid beta (25-35) neurotoxicity in the ferroptosis and necroptosis as modalities of regulated cell death in Alzheimer's disease.

Neuronal cell death as a prominent pathological feature contributes to cognitive decline and memory loss in Alzheimer's disease. We investigated the role of two forms of cell death pathways, ferroptosis and necroptosis, and their interactions following entorhinal cortex (EC) amyloidopathy. The Aß25-35 was bilaterally injected into the rat's EC, and Morris Water Maze was applied to determine spatial performance one week after Aß injection. For evaluation of ferroptosis and necroptosis involvement in Aß induced pathology, ferroptosis inhibitor, Ferrostatin (Fer-1), and necroptosis inhibitor, Necrostatin (Nec-1), were injected into the EC during training days of behavioral test. Our behavioral and histological assessment showed spatial learning and memory impairment, along with neuropathology changes such as cell survival and intracellular Aß deposits in response to EC amyloidopathy, which were ameliorated by treatment with Fer-1 or Nec-1. The expression of ferroptosis key factors GPX4 and SLC7A11 were decreased and the level of TfR was increased following Aß toxicity. Also, Necroptosis pathway related factors RIP1, RIP3, and MLKL were modulated by Aß neurotoxicity. However, application of Fer-1 or Nec-1 could inhibit the hippocampal ferroptosis and necroptosis pathways due to EC amyloidopathy. Our data also demonstrated that Aß-induced necroptosis suppressed by Fer-1, although Nec-1 had no effect on ferroptosis, indicating that ferroptosis pathway is upstream of necroptosis process in the Aß neurotoxicity. Moreover, Aß induced hippocampal mGLUR5 overexpression and reduced level of STIM1/2 recovered by Fer-1 or Nec-1. According to our findings ferroptosis and necroptosis pathways are involved in Aß neurotoxicity through modulation of mGLUR5 and STIM1/2 signaling.

Adverse effects of polystyrene nanoplastic and its binary mixtures with nonylphenol on zebrafish nervous system: From oxidative stress to impaired neurotransmitter system.

Micro(nano)plastics generally co-exist with other chemicals in the environment, resulting in inevitable interaction and combined toxic effects on biota. Nevertheless, little is known regarding the interaction of nanoplastics (NPs) with other co-occurring insults. Hereby, we investigated single and combined effects of chronic exposure (45 days) to polystyrene nanoplastic particulates (PS-NPs) and nonylphenol (4-NP) on zebrafish nervous system. Multiple biomarkers concerning with oxidative-stress [catalase (CAT) activity and reduced glutathione (GSH) level], cholinergic system [Acetylcholinesterase (AchE) activity], glutamatergic system [glutamine synthetase (GS) and glutamate dehydrogenase (GDH) activities], energy metabolism [a-ketoglutarate dehydrogenase (a-KGDH) activity], and histological alterations were assessed. Both single and binary exposure to PS-NPs and 4-NP induced oxidative stress through reducing CAT activity and GSH level, in which a more sever effect was noticed in combined exposure. The AchE activity was significantly inhibited only in single treatment groups demonstrating antagonistic interaction between PS-NPs and 4-NP. Effects on GS activity was also alleviated in binary exposure as compared with single exposure to each contaminant. In addition, an increase in GDH activity was noticed in PS-NPs at 10 and 100 µg/L, and simultaneous presence of PS-NPs and 4-NP with a greater response were observed in combined treatments. PS-NPs and 4-NP either in separate or binary mixtures disrupted energy metabolism by deficiency of α-KGDH activity; however, co-exposure to PS-NPs and 4-NP induced more intense adverse impacts on this parameter. Furthermore, histological analysis revealed that 4-NP and PS-NPs, alone or in combination, reduced neural cells. These findings provide new insight into the neurotoxic effects of binary exposure to PS-NPs and 4-NP at environmentally relevant concentrations. Overall, our findings raise concerns about the presence and toxicity of nano-scale plastic particulates and highlight the importance of investigating the interaction of Micro(nano)plastics with other environmental irritants.

Regulatory Role of PFC Corticotropin-Releasing Factor System in Stress-Associated Depression Disorders: A Systematic Review.

Stress has a substantial role in formation of psychiatric disorders especially depression. Meanwhile, impairment of the prefrontal cortex (PFC) is connected to the executive and cognitive deficits induced by the stress. Given the involvement of the corticotropin-releasing factor (CRF) in stress-related processes and knowing the fact that PFC hosts a lot of CRF receptors and CRF neurotransmissions, it can worth to look at the CRF as a potential treatment for the regulation of depression disorders induced by stress within PFC region. Here, for the first time we aimed to systematically review the effectiveness of intra-PFC CRF system in the modulation of depression dysfunction caused by the stress in clinical and preclinical models/studies. Qualified researches were combined utilizing a comprehensive search of six databases including Scopus, Pubmed, Web of Science, Sciencedirect, APA PsycNet, and Embase in April 2021 and were evaluated through proper methodological quality assessment tools. Results indicate that PFC has a remarkable role in the modulation for stress-induced depression and intra-PFC CRF receptors agonist and antagonist are very considerable for regulating these types of impairments. Specifically, elevation of both CRF immunoreactivity and gene expression were observed in human studies. In the animal studies, mostly immunoreactivity or excitatory/inhibitory currents of CRF within the PFC regulated depression dysfunction. In conclusion, reviewed studies show a positive attitude toward the CRF system in regulation of the stress-induced depression; however, obviously further investigations are required to get closer to the best treatment. Prefrontal cortex corticotropin-releasing factor system regulates stress-induced depression. CRFR1, Corticotropin-releasing factor receptor of type1; PFC, Prefrontal cortex; Minus (-) and Plus (+) signs, dysregulation and upregulation, respectively.

Dynamic changes in kynurenine pathway metabolites in multiple sclerosis: A systematic review.

Background: Multiple sclerosis (MS) is a debilitating neurodegenerative disorder characterized by axonal damage, demyelination, and perivascular inflammatory lesions in the white matter of the central nervous system (CNS). Kynurenine pathway (KP), which is the major route of tryptophan (TRP) metabolism, generates a variety of neurotoxic as well as neuroprotective compounds, affecting MS pathology and the severity of impairments. Alterations in KP have been described not only in MS, but also in various psychiatric and neurodegenerative diseases. The purpose of this systematic review is to investigate the previously reported dysregulation of KP and differences in its metabolites and enzymes in patients with MS compared to healthy control subjects. Method: Electronic databases of PubMed, Scopus, Cochrane Database of Systematic Reviews, and Web of Science were searched to identify studies measuring concentrations of KP metabolites and enzymes in MS patients and control subjects. The following metabolites and enzymes implicated in the KP were investigated: TRP, kynurenine (KYN), kynurenic acid (KYNA), quinolinic acid (QUIN), picolinic acid (PIC), hydroxyindoleacetic acid (HIAA), indoleamine 2,3-dioxygenase (IDO), kynurenine aminotransferase (KAT), and their related ratios. Result: Ten studies were included in our systematic review. Our review demonstrates that IDO expression is reduced in the peripheral blood mononuclear cells (PBMCs) of MS patients compared to healthy controls. Also, increased levels of QUIN and QUIN/KYNA in the serum and cerebrospinal fluid (CSF) of MS patients is observed. Differences in levels of other metabolites and enzymes of KP are also reported in some of the reviewed studies, however there are discrepancies among the included reports. Conclusion: The results of this investigation suggest a possible connection between alterations in the levels of KP metabolite or enzymes and MS. QUIN levels in CSF were higher in MS patients than in healthy controls, suggesting that QUIN may be involved in the pathogenesis of MS. The data indicate that differences in the serum/blood or CSF levels of certain KP metabolites and enzymes could potentially be used to differentiate between MS patients and control subjects.

Dynamic changes in metabolites of the kynurenine pathway in Alzheimer's disease, Parkinson's disease, and Huntington's disease: A systematic Review and meta-analysis.

Background: Tryptophan (TRP) is an essential amino acid that must be provided in the diet. The kynurenine pathway (KP) is the main route of TRP catabolism into nicotinamide adenosine dinucleotide (NAD+), and metabolites of this pathway may have protective or degenerative effects on the nervous system. Thus, the KP may be involved in neurodegenerative diseases. Objectives: The purpose of this systematic review and meta-analysis is to assess the changes in KP metabolites such as TRP, kynurenine (KYN), kynurenic acid (KYNA), Anthranilic acid (AA), 3-hydroxykynurenine (3-HK), 5-Hydroxyindoleacetic acid (5-HIAA), and 3-Hydroxyanthranilic acid (3-HANA) in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) patients compared to the control group. Methods: We conducted a literature search using PubMed/Medline, Scopus, Google Scholar, Web of Science, and EMBASE electronic databases to find articles published up to 2022. Studies measuring TRP, KYN, KYNA, AA, 3-HK, 5-HIAA, 3-HANA in AD, PD, or HD patients and controls were identified. Standardized mean differences (SMDs) were used to determine the differences in the levels of the KP metabolites between the two groups. Results: A total of 30 studies compromising 689 patients and 774 controls were included in our meta-analysis. Our results showed that the blood levels of TRP was significantly lower in the AD (SMD=-0.68, 95% CI=-0.97 to -0.40, p=0.000, I2 = 41.8%, k=8, n=382), PD (SMD=-0.77, 95% CI=-1.24 to -0.30, p=0.001, I2 = 74.9%, k=4, n=352), and HD (SMD=-0.90, 95% CI=-1.71 to -0.10, p=0.028, I2 = 91.0%, k=5, n=369) patients compared to the controls. Moreover, the CSF levels of 3-HK in AD patients (p=0.020) and the blood levels of KYN in HD patients (p=0.020) were lower compared with controls. Conclusion: Overall, the findings of this meta-analysis support the hypothesis that the alterations in the KP may be involved in the pathogenesis of AD, PD, and HD. However, additional research is needed to show whether other KP metabolites also vary in AD, PD, and HD patients. So, the metabolites of KP can be used for better diagnosing these diseases.

Phosphonate analog of 2-oxoglutarate regulates glutamate-glutamine homeostasis and counteracts amyloid beta induced learning and memory deficits in rats.

BACKGROUND: Metabolic alteration is a mainstream concept underlying the cognitive decline in neurodegenerative disorders including Alzheimer's disease (AD). Mitochondrial enzyme α-ketoglutarate dehydrogenase complex (α-KGDHC) seems to play a dual-edged sword role in cytotoxic insult. Here, using succinyl phosphonate (SP), a specific α-KGDHC inhibitor, we aimed to examine its potential action on AD progression. METHODS: Male Wistar rats were assigned to two separate experiments. First, they were bilaterally microinjected into the dorsal CA1 area by amyloid-beta (Aß)25-35 for four consecutive days. Seven days after the last injection, they were trained to acquire Morris Water Maze (MWM) task for three successive days when they were treated with SP after each training session. In the second experiment, SP was administered 30 min after the first Aß microinjection and behavioral tests were performed one week after the last Aß administration. The activity of glutamate dehydrogenase (GDH), and glutamine synthetase (GS), as key enzymes involved in glutamate-glutamine homeostasis and histological assays were evaluated in the hippocampi. RESULTS: Our behavioral results indicated that post-training SP treatment enhanced task acquisition but did not change memory performance in Aß-treated rats. However, administration of SP at the time of Aß injection precludes the deteriorative effect of Aß and neuronal injury on both spatial learning and memory performances indicating its preventive action against Aß pathology at its early stages. Measurement of enzymes activity shows that α-KGDHC activity was reduced in the Aß treated group, and SP administration restored its activity; also, GDH and GS activities were increased and decreased respectively due to Aß, and SP reversed the action of Aß on these enzymes. CONCLUSIONS: This study proposes that SP possibly a promising therapeutic approach to improve memory impairment in AD, especially in the early phases of this disease.

Pre-clinical Studies Identifying Molecular Pathways of Neuroinflammation in Parkinson's Disease: A Systematic Review.

Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by neuroinflammation, formation of Lewy bodies, and progressive loss of dopaminergic neurons in the substantia nigra of the brain. In this review, we summarize evidence obtained by animal studies demonstrating neuroinflammation as one of the central pathogenetic mechanisms of PD. We also focus on the protein factors that initiate the development of PD and other neurodegenerative diseases. Our targeted literature search identified 40 pre-clinical in vivo and in vitro studies written in English. Nuclear factor kappa B (NF-kB) pathway is demonstrated as a common mechanism engaged by neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA), as well as the bacterial lipopolysaccharide (LPS). The α-synuclein protein, which plays a prominent role in PD neuropathology, may also contribute to neuroinflammation by activating mast cells. Meanwhile, 6-OHDA models of PD identify microsomal prostaglandin E synthase-1 (mPGES-1) as one of the contributors to neuroinflammatory processes in this model. Immune responses are used by the central nervous system to fight and remove pathogens; however, hyperactivated and prolonged immune responses can lead to a harmful neuroinflammatory state, which is one of the key mechanisms in the pathogenesis of PD.

Deep brain stimulation for opioid use disorder: A systematic review of preclinical and clinical evidence.

Opioid use disorder (OUD) is a chronic and complex disease characterized by repeated relapses and remissions. Deep brain stimulation (DBS) has been discussed again and again as a potentially helpful neuromodulatory procedure in this context. In this review, for the first time, we intended to systematically identify the positive and negative effects of DBS in human and animal models of opioid dependence to assess the viability of DBS as a treatment of OUD. Eligible studies were incorporated by a comprehensive literature search and evaluated through proper methodological quality assessment tools. Findings showed that the nucleus accumbens was the most stimulated brain target in human and animal studies, and DBS was applied chiefly in the form of high-frequency stimulation (HFS). DBS administration effectively reduced opioid craving and consumption in human and animal subjects dependent on opioids. DBS represents a valuable alternative strategy for treating intractable opioid addiction. Based on our systematic literature analysis, research efforts in this field should be continued.

The Predictive Power of Near-Infrared Spectroscopy in Improving Cognitive Problems in Patients Undergoing Brain Surgeries: A Systematic Review.

One of the main objectives in neurosurgical procedures is the prevention of cerebral ischemia and hypoxia leading to secondary brain injury. Different methods for early detection of intraoperative cerebral ischemia and hypoxia have been used. Near-infrared spectroscopy (NIRS) is a simple, non-invasive method for monitoring cerebral oxygenation increasingly used today. The aim of this study was to systematically review the brain monitoring with NIRS in neurosurgery. The search process resulted in the detection of 324 articles using valid keywords on the electronic databases, including Embase, PubMed, Scopus, Web of Science, and Cochrane Library. Subsequently, the full texts of 34 studies were reviewed, and finally 11 articles (seven prospective studies, three retrospective studies, and one randomized controlled trial) published from 2005 to 2020 were identified as eligible for systematic review. Meta-analysis was not possible due to high heterogeneity in neurological and neurosurgical conditions of patients, expression of different clinical outcomes, and different standard reference tests in the studies reviewed. The results showed that NIRS is a non-invasive cerebral oximetry that provides continuous and measurable cerebral oxygenation information and can be used in a variety of clinical settings.

Comparison of microscopic and endoscopic resection of third-ventricular colloid cysts: A systematic review and meta-analysis.

BACKGROUND AND AIM: Colloid cysts are uncommon benign lesions. There is a lack of consensus regarding the preferred surgical strategy for colloid cyst resection; the technique with the optimal rates of remission, recurrence, mortality, and complications is debatable. MATERIALS AND METHODS: To determine surgical outcomes, we performed a systematic review of the published literature on Colloid cysts. Eligible studies (n = 63) with a prospective or retrospective evaluation of endoscopic or microscopic resection of third ventricle colloid cysts were included, which contained data describing extents of resection, seizures, meningitis, and tumor recurrence. A total of 3143 patients (1741 microscopically and 1402 endoscopically operated) were included in the final analysis. RESULTS: According to the results of the meta-analysis, there was a higher rate of gross total resection (GTR) (98.15% versus 91.29%, p = 0.00), need for shunting (4.75% versus 1.46%, p = 0.04), postoperative complications (20.68% versus 10.42%, P = 0.03), mean operating time (194.18 versus 113.04 min), and duration of hospitalization (7.85 versus 4.69 days) for microscopic resection compared with endoscopic resection. While endoscopic resection is associated with a higher rate of cyst recurrence (1.78% versus 0.00%, P = 0.00), there was no difference in reoperation rate (0.49% for endoscopic versus 0.09% for microscopic resection). CONCLUSION: Microsurgical resection of third ventricle colloid cysts was associated with a higher rate of GTR and a lower rate of recurrence, while there was a lower rate of postoperative complications, duration of surgery, and shorter hospitalization period in the endoscopic group.

Gut Microbiota Modification via Glucagon-like Peptide-1 with Beneficial Neuroprotective Effects.

BACKGROUND: In recent decades, it has been shown that the association between intestinal bacterial imbalance (dysbiosis) and various diseases such as type 2 diabetes can play a role in the development of Alzheimer's and Parkinson's diseases. In this study, the beneficial effects of intestinal microbiota glucagon-like peptide 1 (GLP-1) in cognitive disorders were investigated. METHODS: PubMed-Medline, Web of Science, and Scopus were searched to identify experimental studies based on the bacterial strains along with GLP-1 1 expression in preventing or reducing cognitive impairment. Of the 233 studies, six were eligible for inclusion, and the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool was used to evaluate the risk of bias in individual studies. RESULTS: The results showed that intestinal expression of GLP-1 1 could reduce the intestinal pathogenic genus such as Enterobacteriaceae and was obviously associated with a greater number of beneficial genera such as Lactobacillus and Akkermansia. Also, the neuroprotective effects of Clostridium butyricum with GLP-1 1 in a mice were approved. Therefore, the modulation of the intestinal microbiota, mediated by an increase in the intestinal GLP-1 1 level, consequently improved cognitive function. CONCLUSION: In this review, we have indicated that the gut microbiota, by stimulating the expression of the intestinal hormones like GLP-1 1, and also with a beneficial effect in inhibiting some involved genes in inflammation, can declined the development of cognitive disorders.

The contribution of gut-brain axis to development of neurological symptoms in COVID-19 recovered patients: A hypothesis and review of literature.

The gut microbiota undergoes significant alterations in response to viral infections, particularly the novel SARS-CoV-2. As impaired gut microbiota can trigger numerous neurological disorders, we suggest that the long-term neurological symptoms of COVID-19 may be related to intestinal microbiota disorders in these patients. Thus, we have gathered available information on how the virus can affect the microbiota of gastrointestinal systems, both in the acute and the recovery phase of the disease, and described several mechanisms through which this gut dysbiosis can lead to long-term neurological disorders, such as Guillain-Barre syndrome, chronic fatigue, psychiatric disorders such as depression and anxiety, and even neurodegenerative diseases such as Alzheimer's and Parkinson's disease. These mechanisms may be mediated by inflammatory cytokines, as well as certain chemicals such as gastrointestinal hormones (e.g., CCK), neurotransmitters (e.g., 5-HT), etc. (e.g., short-chain fatty acids), and the autonomic nervous system. In addition to the direct influences of the virus, repurposed medications used for COVID-19 patients can also play a role in gut dysbiosis. In conclusion, although there are many dark spots in our current knowledge of the mechanism of COVID-19-related gut-brain axis disturbance, based on available evidence, we can hypothesize that these two phenomena are more than just a coincidence and highly recommend large-scale epidemiologic studies in the future.

Early repolarization and the severity of coronary artery disease: A case-control study.

BACKGROUND: Early repolarization (ER) is a common finding of the routine electrocardiogram (ECG). The ER usually considered a benign ECG finding, nevertheless a controversy. This study was conducted to investigate the relationship between early repolarization (ER) and the severity of coronary artery disease in patients with a diagnostic coronary angiography. METHODS: This case-control study included ninety patients (45 patients and 45 control groups) with a diagnostic angiography and was conducted in 2015. After obtaining informed consent, patients with angiography for ER were considered as cases and those for other purposes were as controls. Data were analyzed using SPSS software Version 16. A p-value lesser than 0.05 was significant. RESULTS: The frequency of ER was higher in men (75.6%), and there was a significant relationship between sex and ER (P=0.003). The mean age of the patients in the ER group was lower than that of non-ER patients, but not statistically significant (P=0.1). Abnormal angiography was more prevalent in patients with ER than non-ER patients (59.6% vs. 40.4%). ER morphology showed a significant correlation to abnormal angiography and also stenosis severity (P=0.035). CONCLUSION: ER was higher in men than in women. There was a significant correlation between the existence of ER morphology and atherosclerosis severity. Screening programs for ER detection may reduce the risk of arrhythmias and prevent related complications.

Neurological Symptoms, Comorbidities, and Complications of COVID-19: A Literature Review and Meta-Analysis of Observational Studies.

BACKGROUND: Recently, it has been shown that coronavirus disease 2019 (COVID-19), which has caused a pandemic since December 2019, can be accompanied by some neurological disorders. This study aimed to assess the prevalence of the most common neurological symptoms and comorbidities and systematically review the literature regarding the most prevalent neurological complications of COVID-19 infection. METHODS: All relevant studies had been collected from PubMed, Scopus, Embase, and Web of Science databases. All extracted data were analyzed using Stata version 11.2. The I2 index was applied, and a random-effects model or a fixed-effects model was used for pooled estimation to assess the heterogeneity of studies. Furthermore, Egger and Beeg's tests were used to evaluate the publication bias. RESULTS: Fifty-seven studies (26 observational and 31 case reports) were included (including 6,597 COVID-19 patients). The most prevalent general symptoms were fever, cough, and dyspnea with 84.6% (95% CI: 75.3-92.1; I2 = 98.7%), 61.3% (95% CI: 55.3-67.0; I2 = 94.6%), and 34.2% (95% CI: 25.6-43.4; I2 = 97.7%), respectively. Neurological symptoms observed among COVID-19 patients were fatigue, gustatory dysfunction, anorexia, olfactory dysfunction, headache, dizziness, and nausea with 42.9% (95% CI: 36.7-49.3; I2 = 92.8%), 35.4% (95% CI: 11.2-64.4; I2 = 99.2%), 28.9% (95% CI: 19.9-38.8; I2 = 96.3%), 25.3% (95% CI: 1.6-63.4; I2 = 99.6%), 10.1% (95% CI: 2.7-21.0; I2 = 99.1%), 6.7% (95% CI: 3.7-10.5; I2 = 87.5%), and 5.9% (95% CI: 3.1-9.5; I2 = 94.5%). The most prevalent neurological comorbidity in COVID-19 was cerebrovascular disease with 4.3% (95% CI: 2.7-6.3; I2 = 78.7%). CONCLUSION: The most prevalent neurological manifestations of COVID-19 include fatigue, gustatory dysfunction, anorexia, olfactory dysfunction, headache, dizziness, and nausea. Cerebrovascular disorders can either act as a risk factor for poorer prognosis in COVID-19 patients or occur as a critical complication in these patients. Guillain-Barre syndrome, encephalitis, and meningitis have also been reported as complications of COVID-19.