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• The GNRI has the potential prognostic value for patients with ALS. • Lower GNRI were linked with a shorter survival time in patients with ALS. • GNRI was an independent predictor of survival time in patients with ALS. • A lower GNRI was found in bulbar onset patients than in limb onset patients. • The GNRI level was correlated with ALSFRS-R score, onset age, onset site, and FVC%. The geriatric nutritional risk index (GNRI) is a prognostic indicator for several diseases, meanwhile, nutrition and inflammation play important roles in the disease progression of amyotrophic lateral sclerosis (ALS). However, the association between the GNRI and ALS remains unknown. 443 patients diagnosed with ALS were divided into two groups based on the GNRI levels. Associations between GNRI and survival time were analyzed using Kaplan-Meier curves and compared by the log-rank test. Univariate and multivariate analyses were used to assess their prognostic values for survival time. Spearman correlation analysis was used to evaluate the correlation coefficients between GNRI and other clinical variables. No significant differences were found in diagnostic delay between the two groups. The onset age and disease progression rate (DPR) were significantly lower in high GNRI group while forced vital capacity (FVC), revised version of the ALS functional rating scale (ALSFRS-R), serum albumin and body mass index (BMI) were significantly lower in low GNRI group. Lower GNRI levels were linked with shorter ALS patients' survival time by Kaplan-Meier curves. The univariate and multivariate analysis identified the onset age, gender, onset site, diagnostic delay, DRP and GNRI as predictors of survival time in patients with ALS. Nutritional status was closely corelated with ALS progression. The GNRI may be used as a potential prognostic indictor for ALS patients. [ABSTRACT FROM AUTHOR]

Recent studies report that inhibiting TNF-α might be a novel therapeutic strategy for managing brain ischemia. Our previous study reported that mesenchymal stem cell (MSC) transplantation could suppress TNF-α level in both serum and brain. However, the cell type(s) that contribute to the production of TNF-α during ischemia following MSC transplantation has not been well studied. In the present study, we found by fluorescent immunohistochemistry, that 7.95 ± 6.17% of TNF-α+ cells co-expressed Iba-1 in the infarct area of dMCAO rats, a majority of which were found to be CD68+ (activated microglia), suggesting that resident microglial population were not the major source of TNF-α expression. 68.49 ± 5.12% of the TNF-α+ cells in the infarct area could be labeled by GFAP, a specific marker for astrocytes, indicating that resident GFAP+ astrocytes might be the major source of TNF-α expression in the infarct area. In addition to the infarct area, the GFAP+/TNF-α+ double-positive astrocytes accounted for 73.68 ± 7.48% of the TNF-α+ cells in striatum and corpus callosum. The infiltrating cells, including monocytes and lymphocytes, were not the main source of TNF-α either. In response to MSC transplantation, the total TNF-α+ cells as well as the percentage of TNF-α-expressing astrocytes were significantly reduced in the infarct area, suggesting that MSC transplantation could suppress the expression of TNF-α by astrocytes. Taken together, the results demonstrated that resident astrocytes, but not microglia, were the major source of TNF-α expression and could be suppressed by MSC infusion. [Display omitted] • Astrocytes are the main source of TNF-α expression in the infarct area. • TNF-α + astrocytes are regulated by MSC treatment. • Monocytes and lymphocytes are minor sources of TNF-α expression. [ABSTRACT FROM AUTHOR]