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A common neurodegenerative condition that still presents clinical challenges is Multiple Sclerosis (MS). Effective multiple sclerosis treatments are sorely needed in clinical settings. Experimental Autoimmune Encephalomyelitis (EAE) is an animal model of multiple sclerosis, a T-cell-mediated disease. Active T-cells differentiate into the Th9 and Th17 subsets, which are controlled by NF-kB and produce the proinflammatory cytokines IL9 and IL17. Because these cytokines are crucial to the pathophysiology of EAE, they have been used as targets for MS therapy. Caffeic acid phenethyl ester (CAPE) is an active ingredient of propolis that has been shown to have immunomodulatory and anti-inflammatory activities. Mitoxantrone is a synthetic antineoplastic agent and cytotoxic immunosuppressive effect used to treat MS. The study aimed to determine whether the two medications have superior efficacy and effect in the treatment of EAE mouse model MS compared to the other. After inducing EAE in mice, CAPE and mitoxantrone were administered to evaluate this therapeutic effectiveness. ELISA was used to measure IL9, IL17 levels and the activity of NF-kBp56. H&E was used to evaluate cell infiltration T lymphocytes for histopathology of spinal cord tissue. Molecular docking was performed to predict the interaction between CAPE and a cytokine. We found that CAPE has a sufficient effect of reducing the level of IL9, IL17, active NF-kBp56, and inflammatory cell infiltration T-lymphocytes in all groups of mice EAE treated with CAPE. In contrast, mitoxantrone reduced cytokines and cell infiltration, so EAE mice treated with both compounds were observed more improvement than other groups. Based on our findings, two medications demonstrated the same efficacy and effect in EAE mice model MS., whereas CAPE did not statistically reach a significant value. While the combination of two medications has the optimal effect. [ABSTRACT FROM AUTHOR]

Background As the life expectancy of elderly people has drastically increased, the incidence of cardiovascular and cerebrovascular diseases in this population has proportionally grown. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease. Homocysteine has recently been recognized as a contributor to the pathomechanisms involved in cognitive impairment. B vitamins, such as folic acid, are known to be effective in lowering homocysteine levels. Methods We conducted a systematic review and meta-analysis of research on folic acid treatments for vascular cognitive impairment. Only randomized controlled trials studies that compared the efficacy of folic acid with placebo or other interventions were considered, irrespective of publication status, year of publication, and languages. Two independent reviewers searched the Medline via Ovid, EMBASE, and Cochrane Central Register of Controlled Trials (Central) journal databases up to July 2021 and independently appraised the included studies. We used mean difference outcome with 95% confidence intervals (CI) to calculate the change of Mini-Mental State Examination, cognitive function domain, and concentration of homocysteine. Results We found 3 studies comparing folic acid with placebo and 1 study comparing folic acid with other interventions. There is only slight evidence that the Mini-Mental State Examination score in patients who received folic acid increased 0.3 point higher compared with the placebo group after 24 months (95% CI = −0.12 to 0.37; P  = .31). There is very strong evidence that the concentration of homocysteine in the folic acid group became 6.16 μmol/L lower compared with the placebo group after 6 months (95% CI = 2.32 to 8.21 lower; P  < .001). Conclusions Our review shows the effectiveness of folic acid in lowering the plasma homocysteine concentration after 6 months compared with placebo. However, this effect was not accompanied by improvement in cognitive function. Study registration: CRD42020199433 https://www.crd.york.ac.uk/prospero/export_details_pdf.php) [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease, causing muscle paralysis and death from respiratory failure. Effective means to preserve/restore ventilation are necessary to increase the quality and duration of life in ALS patients. At disease end-stage in a rat ALS model (SOD1G93A), acute intermittent hypoxia (AIH) restores phrenic nerve activity to normal levels via enhanced phrenic long-term facilitation (pLTF). Mechanisms enhancing pLTF in end-stage SOD1G93A rats are not known. Moderate AIH-induced pLTF is normally elicited via cellular mechanisms that require the following: Gq-protein-coupled 5-HT2 receptor activation, new BDNF synthesis, and MEK/ERK signaling (the Q pathway). In contrast, severe AIH elicits pLTF via a distinct mechanism that requires the following: Gs-protein-coupled adenosine 2A receptor activation, new TrkB synthesis, and PI3K/Akt signaling (the S pathway). In endstage male SOD1G93A rats and wild-type littermates, we investigated relative Q versus S pathway contributions to enhanced pLTF via intrathecal (C4) delivery of small interfering RNAs targeting BDNF or TrkB mRNA, and MEK/ERK (U0126) or PI3 kinase/Akt (PI828) inhibitors. In anesthetized, paralyzed and ventilated rats, moderate AIH-induced pLTF was abolished by siBDNF and UO126, but not siTrkB or PI828, demonstrating that enhanced pLTF occurs via the Q pathway. Although phrenic motor neuron numbers were decreased in end-stage SOD1G93A rats (~30% survival; p < 0.001), BDNF and phosphorylated ERK expression were increased in spared phrenic motor neurons (p<0.05), consistent with increased Q-pathway contributions to pLTF. Our results increase understanding of respiratory plasticity and its potential to preserve/restore breathing capacity in ALS. [ABSTRACT FROM AUTHOR]