Flaxseed Oil Alleviates Trimethyltin-Induced Cell Injury and Inhibits the Pro-Inflammatory Activation of Astrocytes in the Hippocampus of Female Rats.

Exposure to the neurotoxin trimethyltin (TMT) selectively induces hippocampal neuronal injury and astrocyte activation accompanied with resultant neuroinflammation, which causes severe behavioral, cognitive, and memory impairment. A large body of evidence suggests that flaxseed oil (FSO), as one of the richest sources of essential omega-3 fatty acids, i.e., α-linolenic acids (ALA), displays neuroprotective properties. Here, we report the preventive effects of dietary FSO treatment in a rat model of TMT intoxication. The administration of FSO (1 mL/kg, orally) before and over the course of TMT intoxication (a single dose, 8 mg/kg, i.p.) reduced hippocampal cell death, prevented the activation of astrocytes, and inhibited their polarization toward a pro-inflammatory/neurotoxic phenotype. The underlying protective mechanism was delineated through the selective upregulation of BDNF and PI3K/Akt and the suppression of ERK activation in the hippocampus. Pretreatment with FSO reduced cell death and efficiently suppressed the expression of inflammatory molecules. These beneficial effects were accompanied by an increased intrahippocampal content of n-3 fatty acids. In vitro, ALA pretreatment prevented the TMT-induced polarization of cultured astrocytes towards the pro-inflammatory spectrum. Together, these findings support the beneficial neuroprotective properties of FSO/ALA against TMT-induced neurodegeneration and accompanied inflammation and hint at a promising preventive use of FSO in hippocampal degeneration and dysfunction.

Anti-inflammatory potency of novel ecto-5'-nucleotidase/CD73 inhibitors in astrocyte culture model of neuroinflammation.

Three novel cytosine-derived α,ß-methylene diphosphonates designated MRS4598, MRS4552, and MRS4602 were tested in the range of 1 × 10-9 to 1 × 10-3 M for their efficacy and potency in inhibiting membrane-bound ecto-5'-nucleotidase/CD73 activity in primary astrocytes in vitro. The compounds were also tested for their ability to attenuate the reactive astrocyte phenotype induced by proinflammatory cytokines. The main findings are as follows: A) The tested compounds induced concentration-dependent inhibition of CD73 activity, with maximal inhibition achieved at ∼1 × 10-3M; B) All compounds showed high inhibitory potency, as reflected by IC50 values in the submicromolar range; C) All compounds showed high binding capacity, as reflected by Ki values in the low nanomolar range; D) Among the tested compounds, MRS4598 showed the highest inhibitory efficacy and potency, as reflected by IC50 and Ki values of 0.11 µM and 18.2 nM; E) Neither compound affected astrocyte proliferation and cell metabolic activity at concentrations near to IC50; E) MRS4598 was able to inhibit CD73 activity in reactive astrocytes stimulated with TNF-α and to induce concentration-dependent inhibition of CD73 in reactive astrocytes stimulated with IL-1ß, with an order of magnitude higher IC50 value; F) MRS4598 was the only compound tested that was able to induce shedding of the CD73 from astrocyte membranes and to enhance astrocyte migration in the scratch wound migration assay, albeit at concentration well above its IC50 value. Given the role of CD73 in neurodegenerative diseases, MRS4598, MRS4552, and MRS4602 are promising pharmacological tools for the treatment of neurodegeneration and neuroinflammation.

Psychometric properties of the Croatian version of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25).

PURPOSE: The purpose of the study was to translate, adapt and validate the Croatian version of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) in participants with visual impairment. This study also aims at evaluating the relationship between visual impairment and health-related quality of life (HRQoL). METHODS: The prospective observational study was conducted at the University Hospital Centre Zagreb, Department of Ophthalmology. The sample consisted of 175 patients with four chronic ocular diseases: cataract, glaucoma, diabetic retinopathy and age-related macular degeneration. The translation of the NEI VFQ-25 to Croatian was conducted following the standardised procedure. All participants underwent an ophthalmological examination and completed the NEI VFQ-25 and the Medical Outcomes Study Short Form-36 Questionnaire (SF-36). In order to assess the psychometric properties of the NEI VFQ-25, we calculated Cronbach's α coefficient, intraclass correlation coefficient (ICC), convergent and discriminant validity, as well as criterion and concurrent validity. RESULTS: Results show high internal consistency (Cronbach α range 0.739-0.932) and high test-retest reliability (ICC 0.876-0.975) for all subscales. None of the items had failed either convergent or discriminant validity. Moderate to high Spearman's rho coefficients of correlations were found between best corrected visual acuity and eight subscales in the NEI VFQ-25 (0.430 < ρ < 0.631). Moderate correlations were found between comparable domains in the NEI VFQ-25 and in the SF-36 questionnaire (p < 0.01). CONCLUSION: The Croatian version of the NEI VFQ-25 has very good psychometric properties and can be a useful instrument for assessing vision-related quality of life in Croatian population with chronic ophthalmic diseases.