Influence of ovarian hormones on cortical spreading depression and its suppression by L-kynurenine in rat.

Migraine is sexually dimorphic and associated in 20-30% of patients with an aura most likely caused by cortical spreading depression (CSD). We have previously shown that systemic L-kynurenine (L-KYN), the precursor of kynurenic acid, suppresses CSD and that this effect depends on the stage of the estrous cycle in female rats. The objectives here are to determine the influence of ovarian hormones on KCl-induced CSD and its suppression after L-KYN by directly modulating estradiol or progesterone levels in ovariectomized rats. Adult female rats were ovariectomized and subcutaneously implanted with silastic capsules filled with progesterone or 17β-estradiol mixed with cholesterol, with cholesterol only or left empty. Two weeks after the ovariectomy/capsule implantation, the animals received an i.p. injection of L-KYN (300 mg/kg) or NaCl as control. Thirty minutes later CSDs were elicited by applying KCl over the occipital cortex and recorded by DC electrocorticogram for 1 hour. The results show that both estradiol and progesterone increase CSD frequency after ovariectomy. The suppressive effect of L-KYN on CSD frequency, previously reported in normal cycling females, is not found anymore after ovariectomy, but reappears after progesterone replacement therapy. Taken together, these results emphasize the complex role of sex hormones on cortical excitability. The CSD increase by estradiol and, more surprisingly, progesterone may explain why clinically migraine with aura appears or worsens during pregnancy or with combined hormonal treatments

Multiple Stressor Impacts

This repository contains the regression metadata, the 174 paired-stressor response datasets as well as the R-code used in the study: Birk et al. 2020. Impacts of multiple stressors on freshwater biota across spatial scales and ecosystems. Nat. Ecol. Evol. https://doi.org/10.1038/s41559-020-1216-4 The folder "Data" includes the regression metadata ("0_Metadata.csv") as semicolon-separated values and the file "00_Legend_Metadata.md" specifying the column-headers; the 174 paired-stressor response datasets as semicolon-separated values and the file "01_Legend_CaseIDs.md" specifying the column-headers. Note that the variable details are specified in the file "0_Metadata.csv". The folder "R-script" includes the R-code ("cleancode.R") used to analyse the paired-stressor response datasets, and the related R-functions ("functions.R") embedded in the R-code

Impacts of multiple stressors on freshwater biota across spatial scales and ecosystems

Climate and land-use change drive a suite of stressors that shape ecosystems and interact to yield complex ecological responses (that is, additive, antagonistic and synergistic effects). We know little about the spatial scales relevant for the outcomes of such interactions and little about effect sizes. These knowledge gaps need to be filled to underpin future land management decisions or climate mitigation interventions for protecting and restoring freshwater ecosystems. This study combines data across scales from 33 mesocosm experiments with those from 14 river basins and 22 cross-basin studies in Europe, producing 174 combinations of paired-stressor effects on a biological response variable. Generalized linear models showed that only one of the two stressors had a significant effect in 39% of the analysed cases, 28% of the paired-stressor combinations resulted in additive effects and 33% resulted in interactive (antagonistic, synergistic, opposing or reversal) effects. For lakes, the frequencies of additive and interactive effects were similar for all spatial scales addressed, while for rivers these frequencies increased with scale. Nutrient enrichment was the overriding stressor for lakes, with effects generally exceeding those of secondary stressors. For rivers, the effects of nutrient enrichment were dependent on the specific stressor combination and biological response variable. These results vindicate the traditional focus of lake restoration and management on nutrient stress, while highlighting that river management requires more bespoke management solutions