ABSTRACT
We evaluated the expression of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), ionized calcium binding adaptor protein-1 (Iba-1), and ferritin in rats after single or repeated lipopolysaccharide (LPS) treatment, which is known to induce endotoxin tolerance and glial activation. Male Wistar rats (200-250 g) received ip injections of LPS (100 µg/kg) or saline for 6 days: 6 saline (N = 5), 5 saline + 1 LPS (N = 6) and 6 LPS (N = 6). After the sixth injection, the rats were perfused and the brains were collected for immunohistochemistry. After a single LPS dose, the number of GFAP-positive cells increased in the hypothalamic arcuate nucleus (ARC; 1 LPS: 35.6 ± 1.4 vs control: 23.1 ± 2.5) and hippocampus (1 LPS: 165.0 ± 3.0 vs control: 137.5 ± 2.5), and interestingly, 6 LPS injections further increased GFAP expression in these regions (ARC = 52.5 ± 4.3; hippocampus = 182.2 ± 4.1). We found a higher GS expression only in the hippocampus of the 6 LPS injections group (56.6 ± 0.8 vs 46.7 ± 1.9). Ferritin-positive cells increased similarly in the hippocampus of rats treated with a single (49.2 ± 1.7 vs 28.1 ± 1.9) or repeated (47.6 ± 1.1 vs 28.1 ± 1.9) LPS dose. Single LPS enhanced Iba-1 in the paraventricular nucleus (PVN: 92.8 ± 4.1 vs 65.2 ± 2.2) and hippocampus (99.4 ± 4.4 vs 73.8 ± 2.1), but had no effect in the retrochiasmatic nucleus (RCA) and ARC. Interestingly, 6 LPS increased the Iba-1 expression in these hypothalamic and hippocampal regions (RCA: 57.8 ± 4.6 vs 36.6 ± 2.2; ARC: 62.4 ± 6.0 vs 37.0 ± 2.2; PVN: 100.7 ± 4.4 vs 65.2 ± 2.2; hippocampus: 123.0 ± 3.8 vs 73.8 ± 2.1). The results suggest that repeated LPS treatment stimulates the expression of glial activation markers, protecting neuronal activity during prolonged inflammatory challenges.
Subject(s)
Animals , Male , Rats , Calcium-Binding Proteins/drug effects , Ferritins/drug effects , Glial Fibrillary Acidic Protein/drug effects , Glutamate-Ammonia Ligase/drug effects , Hippocampus/drug effects , Hypothalamus/drug effects , Neuroglia/metabolism , Biomarkers/metabolism , Calcium-Binding Proteins/metabolism , Ferritins/metabolism , Glial Fibrillary Acidic Protein/metabolism , Glutamate-Ammonia Ligase/metabolism , Hippocampus/chemistry , Hippocampus/cytology , Hypothalamus/chemistry , Hypothalamus/cytology , Immunohistochemistry , Lipopolysaccharides , Neuroglia/drug effects , Rats, WistarABSTRACT
A randomized clinical trial examined the efficiency and tolerability of twice weekly versus daily iron supplementation during pregnancy. A total of 370 pregnant women were randomly assigned to receive either daily or twice weekly iron supplementation during pregnancy. There were no significant differences in initial and delivery haemoglobin and haematocrit levels between the 2 groups. Ferritin concentrations were significantly lower in the twice weekly group at delivery, but hypoferritinaemia [ferritin < 15 microg/L] was not observed in either group. The frequency of nausea, vomiting and constipation were significantly lower in the twice weekly group. Birth weight and length were significantly higher in the daily supplemented group. In non-anaemic mothers, a smaller dose of iron may be sufficient and also might prevent the complications of iron excess