Glial cell activity is maintained during prolonged inflammatory challenge in rats

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.