Status epilepticus (SE) triggers pathological changes to hippocampal dendrites that may promote epileptogenesis. The microtubule associated protein 2 (Map2) helps stabilize microtubules of the dendritic cytoskeleton. Recently, we reported a substantial decline in Map2 that coincided with robust microglia accumulation in the CA1 hippocampal region after an episode of SE. A spatial correlation between Map2 loss and reactive microglia was also reported in human cortex from refractory epilepsy. New evidence supports that microglia modulate dendritic structures. Thus, to identify a potential association between SE-induced Map2 and microglial changes, a spatiotemporal profile of these events is necessary. We used immunohistochemistry to determine the distribution of Map2 and the microglia marker IBA1 in the hippocampus after pilocarpine-induced SE from 4 hrs to 35 days. We found a decline in Map2 immunoreactivity in the CA1 area that reached minimal levels at 14 days post-SE and partially increased thereafter. In contrast, maximal microglia accumulation occurred in the CA1 area at 14 days post-SE. Our data indicate that SE-induced Map2 and microglial changes parallel each other’s spatiotemporal profiles. These findings may lay the foundation for future mechanistic studies to help identify potential roles for microglia in the dendritic pathology associated with SE and epilepsy.
Oral supplementation may improve the dietary intake of magnesium, which has been identified as a shortfall nutrient. We conducted a pilot study to evaluate appropriate methods for assessing responses to the ingestion of oral magnesium supplements, including ionized magnesium in whole blood (iMg2+) concentration, serum total magnesium concentration, and total urinary magnesium content. In a single-blinded crossover study, 17 healthy adults were randomly assigned to consume 300 mg of magnesium from MgCl2 (ReMag®, a picosized magnesium formulation) or placebo, while having a low-magnesium breakfast. Blood and urine samples were obtained for the measurement of iMg2+, serum total magnesium, and total urine magnesium, during 24 h following the magnesium supplement or placebo dosing. Bioavailability was assessed using area-under-the-curve (AUC) as well as maximum (Cmax) and time-to-maximum (Tmax) concentration. Depending on normality, data were expressed as the mean ± standard deviation or median (range), and differences between responses to MgCl2 or placebo were measured using the paired t-test or Wilcoxon signed-rank test. Following MgCl2 administration versus placebo administration, we observed significantly greater increases in iMg2+ concentrations (AUC = 1.51 ± 0.96 vs. 0.84 ± 0.82 mg/dL•24h; Cmax = 1.38 ± 0.13 vs. 1.32 ± 0.07 mg/dL, respectively; both p < 0.05) but not in serum total magnesium (AUC = 27.00 [0, 172.93] vs. 14.55 [0, 91.18] mg/dL•24h; Cmax = 2.38 [1.97, 4.01] vs. 2.24 [1.98, 4.31] mg/dL) or in urinary magnesium (AUC = 201.74 ± 161.63 vs. 139.30 ± 92.84 mg•24h; Cmax = 26.12 [12.91, 88.63] vs. 24.38 [13.51, 81.51] mg/dL; p > 0.05). Whole blood iMg2+ may be a more sensitive measure of acute oral intake of magnesium compared to serum and urinary magnesium and may be preferred for assessing supplement bioavailability.
Objectives Most studies used serum magnesium concentration and total urine magnesium as nutrition biomarkers of magnesium, but whether these biomarkers are sensitive to changes in dietary intake of magnesium is uncertain. Whole blood ionized magnesium (iMg2+) is the free bioactive form of magnesium in the body, and therefore it could be more sensitive to the changes in magnesium intake. Thus, we aimed to compare the responses of iMg2+, serum magnesium concentration, and total urine magnesium following an oral dose of magnesium. Methods Healthy adults participated in a randomized, single-blind, placebo-controlled crossover trial. They were randomly assigned to 300 mg of magnesium chloride (MgCl2, ReMag®) or placebo, taken with a low-magnesium breakfast after 8-hours of fasting. Timed blood and urine samples were obtained beginning 15-minutes before breakfast, and then at 0, 0.5, 1, 2, 4, 6, 8, and 24-hours timepoints following breakfast. Pharmacokinetic analyses included area under the curve (AUC), the maximum concentration (Cmax), and the time to maximum concentration (Tmax) for iMg2+, serum magnesium concentration, and total urine magnesium. Data were analyzed using paired t-test and Wilcoxon signed-rank test, and reported as mean ± standard deviation, or as median and range, depending on normality. Results Seventeen participants were included in the data analyses. Responses were observed following MgCl2 compared to placebo for iMg2+ (AUC = 1.51 ± 0.96 vs. 0.84 ± 0.82, and Cmax = 1.38 ± 0.13 vs. 1.32 ± 0.07, both P < 0.05). We saw no response following MgCl2 versus placebo for serum magnesium concentration (AUC = 27.00 [0, 172.93] vs. 14.55 [0, 91.18], and Cmax = 2.38 [1.97, 4.01] vs. 2.24 [1.98, 4.31]), and for total urine magnesium (AUC = 201.74 ± 161.63 vs. 139.30 ± 92.84, and Cmax = 26.12 [12.91, 88.63] vs. 24.38 [13.51, 81.51]), both P > 0.05. Conclusions The response of iMg2+ to a single oral dose of magnesium was more pronounced than the responses of serum magnesium concentration and total urine magnesium. Therefore, iMg2+ may be a more sensitive nutrition biomarker for magnesium intake. Funding Sources Funding for this study was provided through an unrestricted educational grant from Think Healthy Group Inc.
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