Fracturing and tectonic stress drive ultrarapid magma flow into dikes.

Many examples of exposed giant dike swarms can be found where lateral magma flow has exceeded hundreds of kilometers. We show that massive magma flow into dikes can be established with only modest overpressure in a magma body if a large enough pathway opens at its boundary and gradual buildup of high tensile stress has occurred along the dike pathway prior to the onset of diking. This explains rapid initial magma flow rates, modeled up to about 7400 cubic meters per second into a dike ~15-kilometers long, which propagated under the town of Grindavík, Southwest Iceland, in November 2023. Such high flow rates provide insight into the formation of major dikes and imply a serious hazard potential for high-flow rate intrusions that propagate to the surface and transition into eruptions.

Clinical outcomes and health care costs of transferring rural Western Australians for invasive coronary angiography, and a cost-effective alternative care model: a retrospective cross-sectional study.

OBJECTIVES: To examine the severity of coronary artery disease (CAD) in people from rural or remote Western Australia referred for invasive coronary angiography (ICA) in Perth and their subsequent management; to estimate the cost savings were computed tomography coronary angiography (CTCA) offered in rural centres as a first line investigation for people with suspected CAD. DESIGN: Retrospective cohort study. SETTING, PARTICIPANTS: Adults with stable symptoms in rural and remote WA referred to Perth public tertiary hospitals for ICA evaluation during the 2019 calendar year. MAIN OUTCOME MEASURES: Severity and management of CAD (medical management or revascularisation); health care costs by care model (standard care or a proposed alternative model with local CTCA assessment). RESULTS: The mean age of the 1017 people from rural and remote WA who underwent ICA in Perth was 62 years (standard deviation, 13 years); 680 were men (66.9%), 245 were Indigenous people (24.1%). Indications for referral were non-ST elevation myocardial infarction (438, 43.1%), chest pain with normal troponin level (394, 38.7%), and other (185, 18.2%). After ICA assessment, 619 people were medically managed (60.9%) and 398 underwent revascularisation (39.1%). None of the 365 patients (35.9%) without obstructed coronaries (< 50% stenosis) underwent revascularisation; nine patients with moderate CAD (50-69% stenosis; 7%) and 389 with severe CAD (≥ 70% stenosis or occluded vessel; 75.5%) underwent revascularisation. Were CTCA used locally to determine the need for referral, 527 referrals could have been averted (53%), the ICA:revascularisation ratio would have improved from 2.6 to 1.6, and 1757 metropolitan hospital bed-days (43% reduction) and $7.3 million in health care costs (36% reduction) would have been saved. CONCLUSION: Many rural and remote Western Australians transferred for ICA in Perth have non-obstructive CAD and are medically managed. Providing CTCA as a first line investigation in rural centres could avert half of these transfers and be a cost-effective strategy for risk stratification of people with suspected CAD.

Deformation and seismicity decline before the 2021 Fagradalsfjall eruption.

Increased rates of deformation and seismicity are well-established precursors to volcanic eruptions, and their interpretation forms the basis for eruption warnings worldwide. Rates of ground displacement and the number of earthquakes escalate before many eruptions1-3, as magma forces its way towards the surface. However, the pre-eruptive patterns of deformation and seismicity vary widely. Here we show how an eruption beginning on 19 March 2021 at Fagradalsfjall, Iceland, was preceded by a period of tectonic stress release ending with a decline in deformation and seismicity over several days preceding the eruption onset. High rates of deformation and seismicity occurred from 24 February to mid-March in relation to gradual emplacement of an approximately 9-km-long magma-filled dyke, between the surface and 8 km depth (volume approximately 34 × 106 m3), as well as the triggering of strike-slip earthquakes up to magnitude MW 5.64. As stored tectonic stress was systematically released, there was less lateral migration of magma and a reduction in both the deformation rates and seismicity. Weaker crust near the surface may also have contributed to reduced seismicity, as the depth of active magma emplacement progressively shallowed. This demonstrates that the interaction between volcanoes and tectonic stress as well as crustal layering need to be fully considered when forecasting eruptions.

Aeromedical retrieval diagnostic trends during a period of Coronavirus 2019 lockdown.

BACKGROUND: Little is known on the trends of aeromedical retrieval (AR) during social isolation. AIM: To compare the pre, lockdown, and post-lockdown AR patient characteristics during a period of Coronavirus 2019 (COVID-19) social isolation. METHODS: An observational study with retrospective data collection, consisting of AR between 26 January and 23 June 2020. RESULTS: There were 16 981 AR consisting of 1983 (11.7%) primary evacuations and 14 998 (88.3%) inter-hospital transfers, with a population median age of 52 years (interquartile range 29.0-69.0), with 49.0% (n = 8283) of the cohort being male and 38.0% (n = 6399) being female. There were six confirmed and 230 suspected cases of COVID-19, with the majority of cases (n = 134; 58.3%) in the social isolation period. As compared to pre-restriction, the odds of retrieval for the restriction and post-restriction period differed across time between the major diagnostic groups. This included, an increase in cardiovascular retrieval for both restriction and post-restriction periods (odds ratio (OR) 1.12, 95% confidence interval (CI) 1.02-1.24 and OR 1.18 95%, CI 1.08-1.30 respectively), increases in neoplasm in the post restriction period (OR 1.31, 95% CI 1.04-1.64) and increases for congenital conditions in the restriction period (OR 2.56, 95% CI 1.39-4.71). Cardiovascular and congenital conditions had increased rates of priority 1 patients in the restriction and post restriction periods. There was a decrease in endocrine and metabolic disease retrievals in the restriction period (OR 0.72, 95% CI 0.53-0.98). There were lower odds during the post-restriction period for retrievals of the respiratory system (OR 0.78, 95% CI 0.67-0.93), and disease of the skin (OR 0.78, 95% CI 0.6-1.0). Distribution between the 2019 and 2020 time periods differed (P < 0.05), with the lockdown period resulting in a significant reduction in activity. CONCLUSION: The lockdown period resulted in increased AR rates of circulatory and congenital conditions.

Colonization with the commensal fungus Candida albicans perturbs the gut-brain axis through dysregulation of endocannabinoid signaling.

Anxiety disorders are the most prevalent mental health disorder worldwide, with a lifetime prevalence of 5-7 % of the human population. Although the etiology of anxiety disorders is incompletely understood, one aspect of host health that affects anxiety disorders is the gut-brain axis. Adolescence is a key developmental window in which stress and anxiety disorders are a major health concern. We used adolescent female mice in a gastrointestinal (GI) colonization model to demonstrate that the commensal fungus Candida albicans affects host health via the gut-brain axis. In mice, bacterial members of the gut microbiota can influence the host gut-brain axis, affecting anxiety-like behavior and the hypothalamus-pituitary-adrenal (HPA) axis which produces the stress hormone corticosterone (CORT). Here we showed that mice colonized with C. albicans demonstrated increased anxiety-like behavior and increased basal production of CORT as well as dysregulation of CORT production following acute stress. The HPA axis and anxiety-like behavior are negatively regulated by the endocannabinoid N-arachidonoylethanolamide (AEA). We demonstrated that C. albicans-colonized mice exhibited changes in the endocannabinoidome. Further, increasing AEA levels using the well-characterized fatty acid amide hydrolase (FAAH) inhibitor URB597 was sufficient to reverse both neuroendocrine phenotypes in C. albicans-colonized mice. Thus, a commensal fungus that is a common colonizer of humans had widespread effects on the physiology of its host. To our knowledge, this is the first report of microbial manipulation of the endocannabinoid (eCB) system that resulted in neuroendocrine changes contributing to anxiety-like behavior.

Unexpected large eruptions from buoyant magma bodies within viscoelastic crust.

Large volume effusive eruptions with relatively minor observed precursory signals are at odds with widely used models to interpret volcano deformation. Here we propose a new modelling framework that resolves this discrepancy by accounting for magma buoyancy, viscoelastic crustal properties, and sustained magma channels. At low magma accumulation rates, the stability of deep magma bodies is governed by the magma-host rock density contrast and the magma body thickness. During eruptions, inelastic processes including magma mush erosion and thermal effects, can form a sustained channel that supports magma flow, driven by the pressure difference between the magma body and surface vents. At failure onset, it may be difficult to forecast the final eruption volume; pressure in a magma body may drop well below the lithostatic load, create under-pressure and initiate a caldera collapse, despite only modest precursors.

Air retrieval for clot retrieval; time-metrics and outcomes of stroke patients from rural and remote regions air-transported for mechanical thrombectomy at a state stroke unit.

BACKGROUND: Providing thrombectomy services to rural or remote regions with small, dispersed populations presents a particular challenge. Sustaining local thrombectomy services is not viable given the low throughput of cases, therefore large vessel occlusion (LVO) stroke patients require emergent transfer, often by air, to the closest high volume urban thrombectomy unit. The aim of this paper is to present logistical, time-metric data and outcome data on LVO stroke patients that have been aeromedically retrieved for thrombectomy from the vast, 2,500,000-km2 rural catchment of the Western Australian state thrombectomy unit. METHODS: The prospectively collected state thrombectomy registry was reviewed and all patients that underwent thrombectomy for LVO strokes following aeromedical retrieval from remote or rural catchments were identified. Multiple logistic and time-metric data points were recorded and outcomes were compared to a cohort of urban patients treated over the same period. RESULTS: Over a 2-year period 30 patients underwent thrombectomy following aeromedical retrieval, either by helicopter or fixed wing aircraft, from rural and remote regions of Western Australia. The mean aeromedical retrieval distance was 393 km while the maximum retrieval distance was over 2600 km. The mean ictus to recanalization time was 657 min, an mTICI 2b-3 recanalization was achieved in 93% of cases and 62% of anterior circulation, and 50% of posterior circulation LVO stroke patients achieved functional independence at 90-days. Outcome data for rural patients compared favourably to urban patients treated over the same time period. CONCLUSION: With the availability of an efficient aeromedical retrieval service, LVO stroke patients in rural and remote regions can achieve excellent outcomes following transfer to a high volume thrombectomy unit, even if distances involved are very large.

Intellectual disability rights and inclusive citizenship in South Africa: What can a scoping review tell us?

BACKGROUND: Intellectual disability (ID) is the most prevalent disability in the world. People with intellectual disability (PWID) frequently experience extreme violations of numerous human rights. Despite greater prevalence in South Africa than in high-income countries, most ID research currently comes from the Global North. This leaves us with few contextually sensitive studies to draw from to advance inclusive citizenship. OBJECTIVES: Our scoping review aims to investigate pertinent ID rights issues in South Africa, synthesise quantitative and qualitative studies, and provide a synopsis of available evidence on which to base future work. We aim to clarify key concepts, address gaps in the literature and identify opportunities for further research. METHOD: We followed strict eligibility criteria. Medical subject heading terms were entered into seven databases. Seven reviewers worked independently, two per paper. Quantitative and qualitative data extraction forms were designed. We followed Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and registered a protocol. An inductive approach enabled a thematic analysis of selected studies. RESULTS: By following PRISMA guidelines, 82 studies were assessed for eligibility of which 59 were included. Ten sub-themes were integrated into four main themes: the right not to be discriminated against, the right to psychological and bodily integrity, the right to accommodating services and challenges to rights implementation. CONCLUSION: People with intellectual disability face compound difficulties when trying to assert their constitutionally entitled rights. This ongoing project requires serious commitment and action. Statutory obligations to nurture every South African's human rights naturally extend to PWID and their supporters who forge ahead in a disabling environment.

Constant strain accumulation rate between major earthquakes on the North Anatolian Fault.

Earthquakes are caused by the release of tectonic strain accumulated between events. Recent advances in satellite geodesy mean we can now measure this interseismic strain accumulation with a high degree of accuracy. But it remains unclear how to interpret short-term geodetic observations, measured over decades, when estimating the seismic hazard of faults accumulating strain over centuries. Here, we show that strain accumulation rates calculated from geodetic measurements around a major transform fault are constant for its entire 250-year interseismic period, except in the ~10 years following an earthquake. The shear strain rate history requires a weak fault zone embedded within a strong lower crust with viscosity greater than ~1020 Pa s. The results support the notion that short-term geodetic observations can directly contribute to long-term seismic hazard assessment and suggest that lower-crustal viscosities derived from postseismic studies are not representative of the lower crust at all spatial and temporal scales.

Hippocampal corticotropin-releasing hormone neurons support recognition memory and modulate hippocampal excitability.

Corticotropin-releasing hormone (CRH) signaling in the hippocampus has been established to be important for mediating the effects of stress on learning and memory. Given our laboratory's recent characterization of a subset of hippocampal CRH neurons as a novel class of GABAergic interneurons, we hypothesized that these local GABAergic hippocampal CRH neurons may influence hippocampal function. Here we applied an array of molecular tools to selectively label and manipulate hippocampal CRH neurons in mice, in order to assess this interneuron population's impact on hippocampus-dependent behaviors and hippocampal network excitability. Genetically-targeted ablation of hippocampal CRH neurons in vivo impaired object recognition memory and substantially enhanced the severity of kainic acid-induced seizures. Conversely, selective activation of CRH neurons in vitro suppressed the excitability of the mossy fiber-CA3 pathway. Additional experiments are needed to reconcile the functions of GABA and CRH signaling of hippocampal CRH neurons on hippocampal function. However, our results indicate that this interneuron population plays an important role in maintaining adaptive network excitability, and provide a specific circuit-level mechanism for this role.

Inability to suppress the stress-induced activation of the HPA axis during the peripartum period engenders deficits in postpartum behaviors in mice.

The stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis is normally suppressed during pregnancy. Dysregulation of the HPA axis has been proposed to play a role in postpartum depression. However, direct investigation into the relationship between the HPA axis and postpartum depression has been hindered by the lack of useful animal models. Building on our discovery of a role for the K+/Cl-co-transporter, KCC2, in the GABAergic regulation of CRH neurons in the paraventricular nucleus of the hypothalamus (PVN), critical for mounting the body's physiological response to stress, we assessed the role of KCC2 in the regulation of the HPA axis during pregnancy and the postpartum period. Here we demonstrate that the normal suppression of the stress-induced activation of the HPA axis during the peripartum period involves maintenance of KCC2 in the PVN. Mice lacking KCC2 specifically in corticosterone-releasing hormone (CRH) neurons, which govern the activity of the HPA axis (KCC2/Crh mice), exhibit dysregulation of the HPA axis and abnormal postpartum behaviors. Loss of KCC2 specifically in CRH neurons in the PVN is sufficient to reproduce the depression-like phenotype and deficits in maternal behaviors during the postpartum period. Similarly, chemogenetic activation of CRH neurons in the PVN is sufficient to induce abnormal postpartum behaviors and chemogenetic silencing of CRH neurons in the PVN can ameliorate abnormal postpartum behaviors observed in KCC2/Crh mice. This study demonstrates that dysregulation of the HPA axis is sufficient to induce abnormal postpartum behaviors and deficits in maternal behaviors in mice, providing empirical support for a role of HPA axis dysfunction in the pathophysiology of postpartum depression.

Seizure-induced activation of the HPA axis increases seizure frequency and comorbid depression-like behaviors.

Our laboratory recently demonstrated that seizures activate the hypothalamic-pituitary-adrenal (HPA) axis, increasing circulating levels of corticosterone (O'Toole et al., 2013). Given the well-established proconvulsant actions of corticosterone, we hypothesized that seizure-induced activation of the HPA axis may contribute to future seizure susceptibility. Further, since hypercortisolism is associated with depression, we propose that seizure-induced activation of the HPA axis may contribute to comorbid depression and epilepsy. To test this hypothesis, we generated mice lacking the GABAA receptor (GABAAR) δ subunit specifically in corticotropin-releasing hormone (CRH) neurons (Gabrd/Crh mice), which exhibit hyporeactivity of the HPA axis (Lee et al., 2014). Gabrd/Crh mice exhibit blunted seizure-induced elevations in corticosterone, establishing a useful tool to investigate the contribution of HPA axis dysfunction on epilepsy and associated comorbidities. Interestingly, Gabrd/Crh mice exhibit decreased acute seizure susceptibility following kainic acid (KA) administration. Furthermore, chronically epileptic Gabrd/Crh mice exhibit a decrease in both spontaneous seizure frequency and depression-like behaviors compared with chronically epileptic Cre-/- littermates. Seizure susceptibility and associated depression-like behaviors can be restored to wild type levels by treating Gabrd/Crh mice with exogenous corticosterone. Similarly, chemogenetic activation of CRH neurons in the paraventricular nucleus (PVN) is sufficient to increase seizure susceptibility; whereas, chemogenetic inhibition of CRH neurons in the PVN of the hypothalamus is sufficient to decrease seizure susceptibility and depression-like behaviors in chronically epileptic mice. These data suggest that seizure-induced activation of the HPA axis promotes seizure susceptibility and comorbid depression-like behaviors, suggesting that the HPA axis may be a novel target for seizure control.

A decreasing glacier mass balance gradient from the edge of the Upper Tarim Basin to the Karakoram during 2000-2014.

In contrast to the glacier mass losses observed at other locations around the world, some glaciers in the High Mountains of Asia appear to have gained mass in recent decades. However, changes in digital elevation models indicate that glaciers in Karakoram and Pamir have gained mass, while recent laser altimetry data indicate mass gain centred on West Kunlun. Here, we obtain results that are essentially consistent with those from altimetry, but with two-dimensional observations and higher resolution. We produced elevation models using radar interferometry applied to bistatic data gathered between 2011 and 2014 and compared them to a model produced from bistatic data collected in 2000. The glaciers in West Kunlun, Eastern Pamir and the northern part of Karakoram experienced a clear mass gain of 0.043 ± 0.078~0.363 ± 0.065 m w.e. yr-1. The Karakoram showed a near-stable mass balance in its western part (-0.020 ± 0.064 m w.e. yr-1), while the Eastern Karakoram showed mass loss (-0.101 ± 0.058 m w.e. yr-1). Significant positive glacier mass balances are noted along the edge of the Upper Tarim Basin and indicate a decreasing gradient from northeast to southwest.

Gradual caldera collapse at Bárdarbunga volcano, Iceland, regulated by lateral magma outflow.

Large volcanic eruptions on Earth commonly occur with a collapse of the roof of a crustal magma reservoir, forming a caldera. Only a few such collapses occur per century, and the lack of detailed observations has obscured insight into the mechanical interplay between collapse and eruption. We use multiparameter geophysical and geochemical data to show that the 110-square-kilometer and 65-meter-deep collapse of Bárdarbunga caldera in 2014-2015 was initiated through withdrawal of magma, and lateral migration through a 48-kilometers-long dike, from a 12-kilometers deep reservoir. Interaction between the pressure exerted by the subsiding reservoir roof and the physical properties of the subsurface flow path explain the gradual, near-exponential decline of both collapse rate and the intensity of the 180-day-long eruption.

Reduced tonic inhibition in the dentate gyrus contributes to chronic stress-induced impairments in learning and memory.

It is well established that stress impacts the underlying processes of learning and memory. The effects of stress on memory are thought to involve, at least in part, effects on the hippocampus, which is particularly vulnerable to stress. Chronic stress induces hippocampal alterations, including but not limited to dendritic atrophy and decreased neurogenesis, which are thought to contribute to chronic stress-induced hippocampal dysfunction and deficits in learning and memory. Changes in synaptic transmission, including changes in GABAergic inhibition, have been documented following chronic stress. Recently, our laboratory demonstrated shifts in EGABA in CA1 pyramidal neurons following chronic stress, compromising GABAergic transmission and increasing excitability of these neurons. Interestingly, here we demonstrate that these alterations are unique to CA1 pyramidal neurons, since we do not observe shifts in EGABA following chronic stress in dentate gyrus granule cells. Following chronic stress, there is a decrease in the expression of the GABAA receptor (GABAA R) δ subunit and tonic GABAergic inhibition in dentate gyrus granule cells, whereas there is an increase in the phasic component of GABAergic inhibition, evident by an increase in the peak amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). Given the numerous changes observed in the hippocampus following stress, it is difficult to pinpoint the pertinent contributing pathophysiological factors. Here we directly assess the impact of a reduction in tonic GABAergic inhibition of dentate gyrus granule cells on learning and memory using a mouse model with a decrease in GABAA R δ subunit expression specifically in dentate gyrus granule cells (Gabrd/Pomc mice). Reduced GABAA R δ subunit expression and function in dentate gyrus granule cells is sufficient to induce deficits in learning and memory. Collectively, these findings suggest that the reduction in GABAA R δ subunit-mediated tonic inhibition in dentate gyrus granule cells contributes, at least in part, to deficits in learning and memory associated with chronic stress. These findings have significant implications regarding the pathophysiological mechanisms underlying impairments in learning and memory associated with stress and suggest a role for GABAA R δ subunit containing receptors in dentate gyrus granule cells. © 2016 Wiley Periodicals, Inc.

Characterization of a novel subtype of hippocampal interneurons that express corticotropin-releasing hormone.

A subset of corticotropin-releasing hormone (CRH) neurons was previously identified in the hippocampus with unknown function. Here we demonstrate that hippocampal CRH neurons represent a novel subtype of interneurons in the hippocampus, exhibiting unique morphology, electrophysiological properties, molecular markers, and connectivity. This subset of hippocampal CRH neurons in the mouse reside in the CA1 pyramidal cell layer and tract tracing studies using AAV-Flex-ChR2-tdTomato reveal dense back-projections of these neurons onto principal neurons in the CA3 region of the hippocampus. These hippocampal CRH neurons express both GABA and GAD67 and using in vitro optogenetic techniques, we demonstrate that these neurons make functional connections and release GABA onto CA3 principal neurons. The location, morphology, and importantly the functional connectivity of these neurons demonstrate that hippocampal CRH neurons represent a unique subtype of hippocampal interneurons. The connectivity of these neurons has significant implications for hippocampal function.

Crustal movements due to Iceland's shrinking ice caps mimic magma inflow signal at Katla volcano.

Many volcanic systems around the world are located beneath, or in close proximity to, ice caps. Mass change of these ice caps causes surface movements, which are typically neglected when interpreting surface deformation measurements around these volcanoes. These movements can however be significant, and may closely resemble movements due to magma accumulation. Here we show such an example, from Katla volcano, Iceland. Horizontal movements observed by GPS on the flank of Katla have led to the inference of significant inflow of magma into a chamber beneath the caldera, starting in 2000, and continuing over several years. We use satellite radar interferometry and GPS data to show that between 2001 and 2010, the horizontal movements seen on the flank can be explained by the response to the long term shrinking of ice caps, and that erratic movements seen at stations within the caldera are also not likely to signify magma inflow. It is important that interpretations of geodetic measurements at volcanoes in glaciated areas consider the effect of ice mass change, and previous studies should be carefully reevaluated.

Segmented lateral dyke growth in a rifting event at Bárðarbunga volcanic system, Iceland.

Crust at many divergent plate boundaries forms primarily by the injection of vertical sheet-like dykes, some tens of kilometres long. Previous models of rifting events indicate either lateral dyke growth away from a feeding source, with propagation rates decreasing as the dyke lengthens, or magma flowing vertically into dykes from an underlying source, with the role of topography on the evolution of lateral dykes not clear. Here we show how a recent segmented dyke intrusion in the Bárðarbunga volcanic system grew laterally for more than 45 kilometres at a variable rate, with topography influencing the direction of propagation. Barriers at the ends of each segment were overcome by the build-up of pressure in the dyke end; then a new segment formed and dyke lengthening temporarily peaked. The dyke evolution, which occurred primarily over 14 days, was revealed by propagating seismicity, ground deformation mapped by Global Positioning System (GPS), interferometric analysis of satellite radar images (InSAR), and graben formation. The strike of the dyke segments varies from an initially radial direction away from the Bárðarbunga caldera, towards alignment with that expected from regional stress at the distal end. A model minimizing the combined strain and gravitational potential energy explains the propagation path. Dyke opening and seismicity focused at the most distal segment at any given time, and were simultaneous with magma source deflation and slow collapse at the Bárðarbunga caldera, accompanied by a series of magnitude M > 5 earthquakes. Dyke growth was slowed down by an effusive fissure eruption near the end of the dyke. Lateral dyke growth with segment barrier breaking by pressure build-up in the dyke distal end explains how focused upwelling of magma under central volcanoes is effectively redistributed over long distances to create new upper crust at divergent plate boundaries.

Seizure-induced disinhibition of the HPA axis increases seizure susceptibility.

Stress is the most commonly reported precipitating factor for seizures. The proconvulsant actions of stress hormones are thought to mediate the effects of stress on seizure susceptibility. Interestingly, epileptic patients have increased basal levels of stress hormones, including corticotropin-releasing hormone (CRH) and corticosterone, which are further increased following seizures. Given the proconvulsant actions of stress hormones, we proposed that seizure-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis may contribute to future seizure susceptibility. Consistent with this hypothesis, our data demonstrate that pharmacological induction of seizures in mice with kainic acid or pilocarpine increases circulating levels of the stress hormone, corticosterone, and exogenous corticosterone administration is sufficient to increase seizure susceptibility. However, the mechanism(s) whereby seizures activate the HPA axis remain unknown. Here we demonstrate that seizure-induced activation of the HPA axis involves compromised GABAergic control of CRH neurons, which govern HPA axis function. Following seizure activity, there is a collapse of the chloride gradient due to changes in NKCC1 and KCC2 expression, resulting in reduced amplitude of sIPSPs and even depolarizing effects of GABA on CRH neurons. Seizure-induced activation of the HPA axis results in future seizure susceptibility which can be blocked by treatment with an NKCC1 inhibitor, bumetanide, or blocking the CRH signaling with Antalarmin. These data suggest that compromised GABAergic control of CRH neurons following an initial seizure event may cause hyperexcitability of the HPA axis and increase future seizure susceptibility.