The effects of melatonin supplementation on neurobehavioral outcomes and clinical severity in rodent models of multiple sclerosis; a systematic review and meta-analysis.

BACKGROUND: Through the antioxidant and anti-inflammation pathways, melatonin is proposed as a safe and effective intervention in neurological diseases. This study aims to evaluate the effects of melatonin supplementation on the neurobehavioral and clinical outcomes in animal models of multiple sclerosis (MS). METHODS: This study was conducted following the PRISMA statement. Animal studies that reported the effects of melatonin in preclinical MS models, including the experimental autoimmune encephalomyelitis (EAE) and cuprizone model for demyelination are included in this study. A systematic search in PubMed, Web of Science, Embase, and Scopus up was conducted in April 2023. The collaborative Approach to Meta-Analysis and Review of Animal Experimental Studies (CAMARADES) critical appraisal tool was used for the quality assessment of the studies and the quantitative synthetizes were conducted using the comprehensive meta-analysis software. RESULTS: Out of 542 studies, finally 21 studies, including 14 studies in the EAE model and 7 studies of the toxic demyelination method with cuprizone were included. The route of administration was intraperitoneal in 18 studies, oral in 2 studies, and subcutaneous in 1 study. The quantitative synthesis of the EAE clinical severity scale was associated with significant differences (standardized mean difference [SDM]: - 2.52; - 3.61 to - 1.42; p value < 0.01). In subgroup analyses, the difference was statistically significant in the mouse subgroup (SMD: - 2.60; - 3.74 to - 1.46; p value < 0.01). DISCUSSION: This study encountered that melatonin may be associated with improved behavioral and cognitive outcomes of preclinical models of MS with acceptable safety profiles. FUNDING: The research was supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 71005).

Sericin Improves Memory Impairment Via Activation of the PKA-CREB-BDNF Signaling Pathway and Suppression of Oxidative Stress in Ovariectomized Mice.

Menopause results in estrogen hormone deficiency which causes changes in brain morphology and cognitive impairments. The risk of breast and ovarian cancer increases with estrogen therapy. Thus, finding a substitute treatment option for women in menopause is necessary. In the current study, the impact of chronic sericin treatment (200 mg/kg/day for 6 weeks, gavage) on memory process, oxidative stress markers, synaptic neurotransmission, and acetylcholinesterase (AChE) activity in the hippocampus (HIP) of ovariectomized (OVX) mice was examined and compared to the effects of 17ß-estradiol (Es; 20 µg/kg, s.c.). The results demonstrated that sericin and Es administration improved spatial and recognition memory of the OVX animals in the both Lashley III maze and novel object recognition tests. Moreover, sericin-treated OVX mice showed decreased ROS levels, increased endogenous antioxidant defense capacity, and decreased AChE activity in the HIP. Additionally, sericin and Es therapy up-regulated pre-and-post-synaptic protein markers and increased BDNF, CREB, and protein kinase A (PKA) protein expressions in the HIP of OVX mice. Overall, the activation of the PKA-CREB-BDNF signaling pathway by sericin can provide protection against OVX-induced cognitive dysfunction, making it a potential alternative for managing cognitive deficits in postmenopausal women.

Clinical efficacy and safety of melatonin supplementation in multiple sclerosis: a systematic review.

BACKGROUND: Melatonin is a neurohormone secreted predominantly by the pineal gland that is demonstrated to be associated with the pathogenesis of multiple sclerosis (MS). This research desires to evaluate the tolerability and beneficial effects of exogenous melatonin supplementations in patients with MS. METHODS: This study was executed following the PRISMA 2020 statement. Both observational and interventional studies which reported the clinical effectiveness and/or safety of melatonin supplementation in patients with MS were included in this systematic review. Ovid, PubMed, Scopus, Embase, and Web of Science databases were searched and the risk of bias in included studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools based on study design. RESULTS: Out of 1304 results of database searches, finally, 14 articles, including 7 randomized controlled trials (RCTs), 6 case-control studies, and one quasi-experimental study, were included based on the full-text review. Included phenotypes of MS were mostly relapsing-remitting MS (RRMS) (in 11 studies); it was secondary progressive MS (SPMS) in only one study, and two other studies had a mixture of the different phenotypes. The course of treatment with melatonin supplementation was between 2 weeks and 12 months. There were no substantial safety issues. Although melatonin was associated with enhanced oxidative stress and inflammation status, concerning the clinical benefits, limited studies suggested improvements in sleep conditions, cognitive outcomes, and fatigue in MS. DISCUSSION: There are insufficient data to support the regular melatonin prescription in MS. Limitations such as the small number of included studies, the diversity of the dosage, route, and duration of melatonin administration, and the diversity of assessment tests lead to unconvincing findings in this study. There is a need for future studies to achieve a comprehensive judgment on this subject.

Gliomatosis cerebri with blindness: A case report with literature review.

Cerebral gliomatosis (GC) is a rare diffuse infiltrative growth pattern of glioma with nonspecific clinical manifestations like visual impairment that may involve bilateral temporal lobes. Herpes simplex encephalitis (HSE) and limbic encephalitis (LE) can also lead to temporal lobe involvement. Differentiating these entities is necessary for patients with misleading presentations and imaging findings. To the best of our knowledge, this is the third case of GC presenting with blindness. The patient was a 35 years-old male in a drug rehabilitation center for heroin addiction. He presented with a headache, a single episode of seizure, and a 2-month history of bilateral decrease in visual acuity, which had acutely worsened. Magnetic resonance imaging (MRI) and computed tomography (CT) showed bilateral temporal lobe involvement. Ophthalmological studies showed bilateral papilledema, absence of visual evoked potential, and thickening of the retinal nerve fiber layer. Due to this clinical presentation, normal laboratory data, and suspicious MRI findings, further investigation with magnetic resonance spectroscopy (MRS) was performed. Results showed a greatly increased ratio of choline to creatinine(Cr) or N-acetyl aspartate (NAA), suggesting a neoplastic nature of the disease. Subsequently, the patient was referred for a brain tissue biopsy with a suspicion of malignancy. The pathology results revealed adult-type diffuse glioma with isocitrate dehydrogenase (IDH) mutation. Bilateral blindness, as well as bilateral temporal lobe involvement, each has many different causes. However, as demonstrated in this study, adult-type diffuse glioma must be considered a rare cause of concomitant bilateral temporal lobe involvement and blindness.

Effects of underlying heart failure on outcomes of COVID-19; a systematic review and meta-analysis.

Background: The risk for worse outcomes of COVID-19 (Coronavirus 2019 disease) is higher in patients with cardiac conditions. In this study, we aim to investigate the risks of COVID-19-induced conditions in cases with underlying heart failure. Methods: We systematically searched PubMed, Scopus, Ovid, ProQuest, Web of Science, and the Cochrane library, to collect the English language articles that investigated patients with underlying heart failure who get infected by COVID-19. The second version of comprehensive meta-analysis (CMA.2) software was used to conduct the meta-analysis. Results: From 5997 publications, our eligibility criteria were met by 27 studies. Overall, outcomes investigated in all studies include but are not limited to mortality rate, length of hospitalization, need for Intensive care unit (ICU) admission, need for mechanical ventilation, and major cardiovascular conditions. Regarding mortality heart failure patients were more susceptible to death (OR:2.570, 95%CI: 2.085 to 3.169; p-value:<0.001). Also in heart failure patients, the risk of mechanical ventilation was higher (OR:1.707, 95%CI: 1.113 to 2.617; p-value: 0.014). Conclusion: Pre-existing heart failure is associated with the increased risk of mortality and the need for mechanical ventilation while getting infected with COVID-19. Finding an answer to determine the risk of hospitalization, length of stay, readmission rate, and multiorgan failure is necessary for further development of preventive care and making a plan for providing optimal healthcare facilities for these patients.