Context: Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuropathologic conditions. Objective:In vivo neuroprotective effects of EA on cuprizone (cup)-induced demyelination were evaluated. Material and methods: C57BL/6 J mice were fed with chow containing 0.2% cup for 4 weeks to induce oligodendrocytes (OLGs) depletion predominantly in the corpus callosum (CC). EA was administered at different doses (40 or 80 mg/kg body weight/day/i.p.) from the first day of cup diet. Oligodendrocytes apoptosis [TUNEL assay and myelin oligodendrocyte glycoprotein (MOG+)/caspase-3+ cells), gliosis (H&E staining, glial fibrillary acidic protein (GFAP+) and macrophage-3 (Mac-3+) cells) and inflammatory markers (interleukin 17 (IL-17), interleukin 11 (IL-11) and stromal cell-derived factor 1 α (SDF-1α) or CXCL12] during cup intoxication were examined. Results: High dose of EA (EA-80) increased mature oligodendrocytes population (MOG+ cells, p < 0.001), and decreased apoptosis (p < 0.05) compared with the cup mice. Treatment with both EA doses did not show any considerable effects on the expression of CXCL12, but significantly down-regulated the expression of IL-17 and up-regulated the expression of IL-11 in mRNA levels compared with the cup mice. Only treatment with EA-80 significantly decreased the population of active macrophage (MAC-3+ cells, p < 0.001) but not reactive astrocytes (GFAP+ cells) compared with the cup mice. Discussion and conclusion: In this model, EA-80 effectively reduces lesions via reduction of neuroinflammation and toxic effects of cup on mature OLGs. EA is a suitable therapeutic agent for moderate brain damage in neurodegenerative diseases such as multiple sclerosis.
1 October 2017 in Progress in Neuro-Psychopharmacology and Biological Psychiatry
Purpose. Since fear of falling may be one of the main problems in people with Parkinson’s disease (PD), its assessment with valid tools is necessary in both drug phases. This study was carried out to investigate the psychometric attributes of the Fall Efficacy Scale-International (FES-I) in people with PD, both in On and Off phases. Methods. One hundred twenty-four patients with PD (mean age ± standard deviation, 60.33 ± 12.59 years) were assessed with the FES-I, both in On- and Off-drug phases. Dimensionality, internal consistency, and test-retest reliability were, respectively, explored by means of factor analysis, Cronbach’s alpha, and Intraclass Correlation Coefficient. Convergent validity of FES-I was established with Visual Analog Scale-Fear of Falling, Berg Balance Scale, and Functional Reach Test. Parkinson’s Disease Questionnaire-39 and Unified Parkinson Disease Rating Scale-Activities of Daily Living were also applied. Discriminative validity was tested between patients with and without a history of falling. Results. Factor analysis showed two factors for On- and one factor for Off-drug phase. Internal consistency (α = 0.96, On phase; 0.98, Off phase) and test-retest reliability (0.94; 0.91) were satisfactory in both drug phases. There was a moderate/high correlation (rS = |0.50–0.70|) between FES-I and Visual Analog Scale-Fear of Falling, Berg Balance Scale, and Functional Reach Test. Parkinson’s Disease Questionnaire-39 and Unified Parkinson Disease Rating Scale-Activities of Daily Living were achieved in both drug phases too. The sensitivity of FES-I to discriminate Parkinson’s disease with and without falls showed moderate effect size in both phases. Conclusion. This study verified that FES-I is unidimensional, reliable, and valid to measure the Fear of Falling during On- and Off-drug phases in people with PD.
Although anxiety is a common non-motor outcome of Parkinson's disease (PD) affecting 40% of patients, little attention has been paid so far to its effects on balance impairment and postural control. Improvement of postural control through focusing on the environment (i.e. external focus) has been reported, but the role of anxiety, as a confounding variable, remains unclear. This study aimed to investigate the influence of anxiety and attentional focus instruction on the standing postural control of PD patients. Thirty-four patients with PD (17 with high anxiety (HA-PD) and 17 with low anxiety (LA-PD)), as well as 17 gender- and age-matched healthy control subjects (HC) participated in the study. Postural control was evaluated using a combination of two levels of postural difficulty (standing on a rigid force plate surface with open eyes (RO) and standing on a foam surface with open eyes (FO)), as well as three attentional focus instructions (internal, external and no focus). Only the HA-PD group demonstrated significant postural control impairment as compared to the control, as indicated by significantly greater postural sway measures. Moreover, external focus significantly reduced postural sway in all participants especially during the FO condition. The results of the current study provide evidence that anxiety influences balance control and postural stability in patients with PD, particularly those with high levels of anxiety. The results also confirmed that external focus is a potential strategy that significantly improves the postural control of these patients. Further investigation of clinical applicability is warranted towards developing effective therapeutic and rehabilitative treatment plans.
1 March 2018 in Toxicology and Applied Pharmacology