Perinatal hair cortisol concentrations linked to psychological distress and unpredicted birth complications.

Maternal well-being and stress during the perinatal period have been hypothesized to influence birth outcomes and the postnatal development of offspring. In the present study, we explored whether hair cortisol concentration (HCC) was related to symptoms of psychological distress during the perinatal period and with unpredicted birth complications (UBCs). Surveys measuring symptoms of perceived stress, state/trait anxiety, and depression were collected from 53 participants (mean age = 31.1, SD = 4.04; 83% Caucasian, 17% other races) during the third trimester and again at two and six months after birth, 24.5% of which reported UBCs. In a subset of participants, we measured HCC in hair samples collected during the third trimester (27-39 weeks) and six months after birth. Compared to participants reporting normal births, those reporting UBCs had significantly elevated composite stress, anxiety, and depression (SAD) scores two months after birth, but scores decreased by six months postpartum. During the third trimester, HCC was positively associated with reported SAD scores, and HCC was elevated in participants reporting birth complications. Logistic regression showed HCC, but not SAD scores, predicted UBCs (p = 0.023, pseudo R2= 19.7%). Repeated measures MANOVA showed HCC varied over the perinatal period depending on both SAD scores reported at two months postpartum and the experience of UBCs; but when SAD scores reported at six months postpartum were included in the model, the association between HCC and SAD scores and the influence of UBCs was diminished. Although generalizability is limited by our relatively small, homogeneous sample, findings support a positive association between reported psychological distress and HCC during pregnancy and at two months postpartum. We also report a novel finding that chronically elevated cortisol concentrations during pregnancy were related to the risk of UBCs and remain elevated through the early postpartum period, suggesting the importance of monitoring both psychological distress and HCC during the perinatal period.

Medical Encounters and Treatment Outcomes in Ironman-Distance Triathlon.

PURPOSE: This study aimed to examine the injury and illness characteristics, treatments, and outcomes at elite ultraendurance triathlon events. METHODS: We quantified participant demographics, injury types, treatments, and disposition for medical encounters at 27 Ironman-distance triathlon championships from 1989 to 2019. We then calculated the likelihood of concurrent medical complaints in each encounter. RESULTS: We analyzed 10,533 medical encounters among 49,530 race participants for a cumulative incidence of 221.9/1000 participants (95% confidence interval [CI] = 217.7-226.2). Younger (<35 yr; 259.3/1000, 95% CI = 251.6-267.2) and older athletes (70+ yr; 254.0/1000, 95% CI = 217.8-294.4) presented to the medical tent at higher rates than middle-age adults (36-69 yr; 180.1/1000, 95% CI = 175.4-185.0). Female athletes also presented at higher rates when compared with males (243.9/1000, 95% CI = 234.9-253.2 vs 198.0/1000, 95% CI = 193.4-202.6). The most common complaints were dehydration (438.7/1000, 95% CI = 426.2-451.6) and nausea (400.4/1000, 95% CI = 388.4-412.6). Intravenous fluid was the most common treatment (483/1000; 95% CI = 469.8-496.4). Of the athletes who received medical care, 116.7/1000 (95% CI = 110.1-123.4) did not finish the race, and 17.1/1000 (95% CI = 14.7-19.8) required hospital transport. Athletes rarely presented with an isolated medical condition unless their injury was dermatologic or musculoskeletal in nature. CONCLUSIONS: Ultraendurance triathlon events have high rates of medical encounters among female athletes, as well as both younger and older age categories. Gastrointestinal and exertional-related symptoms are among the most common complaints. Intravenous infusions were the most common treatment after basic medical care. Most athletes entering the medical tent finished the race, and a small percentage were dispatched to the hospital. A more thorough understanding of common medical occurrences, including concurrent presentations and treatments, will allow for improved care and optimal race management.

Clinical presentation of exercise-associated hyponatremia in male and female IRONMAN® triathletes over three decades.

PURPOSE: Exercise-associated hyponatremia (EAH) is common in ultra-endurance events and severe cases are more common in females. The purpose of this paper is to compare the clinical presentation of EAH between male and female triathletes in ultra-endurance competitions. METHODS: Medical records with sodium concentrations (n = 3138) from the IRONMAN® World Championships over the timeframe of 1989-2019 were reviewed for both male (n = 2253) and female (n = 885) competitors. Logistic regression was used to explore the relationships between sex, sodium concentration, and various clinical presentations. RESULTS: When comparing male and female triathletes, clinical variables found to have a different relationship with sodium concentration include altered mental status (inversely related in males and not related in females), abdominal pain, muscle cramps, hypotension, and tachycardia (directly related in males and not related in females), and vomiting and hypokalemia (not related in males and inversely related in females). Overall, males lost significantly more weight than females, and notably, approximately half of all athletes were dehydrated and lost weight. CONCLUSIONS: Altered mental status, vomiting, abdominal pain, muscle cramps, hypotension, tachycardia, and hyperkalemia appear to present differently between sexes when comparing hyponatremic to eunatremic athletes. Although overhydration is the most common etiology of hypervolemic hyponatremia, hypovolemic hyponatremia comprises a significant amount of hyponatremic triathletes. Further understanding of how EAH presents helps athletes and medical professionals identify it early and prevent life-threatening complications.

Environmental pharmacology-Dosing the environment: IUPHAR review 36.

Pesticide action is predominantly measured as a toxicological outcome, with pharmacological impact of sublethal doses on bystander species left largely undocumented. Likewise, chronic exposure, which often results in responses different from acute administration, has also been understudied. In this article, we propose the application of standard pharmacological principles, already used to establish safe clinical dosing regimens in humans, to the 'dosing of the environment'. These principles include relating the steady state dose of an agent to its beneficial effects (e.g. pest control), while minimising harmful impacts (e.g. off-target bioactivity in beneficial insects). We propose the term 'environmental therapeutic window', analogous to that used in mammalian pharmacology, to guide risk assessment. To make pharmacological terms practically useful to environmental protection, quantitative data on pesticide action need to be made available in a freely accessible database, which should include toxicological and pharmacological impacts on both target and off-target species.

Electronic blood glucose monitoring impacts on provider and patient behavior.

OBJECTIVE: Recent technological development along with the constraints imposed by the coronavirus disease 2019 (COVID-19) pandemic have led to increased availability of patient-generated health data. However, it is not well understood how to effectively integrate this new technology into large health systems. This article seeks to identify interventions to increase utilization of electronic blood glucose monitoring for patients with diabetes. MATERIALS AND METHODS: A large randomized controlled trial tested the impact of multiple interventions to promote use of electronic blood glucose tracking. The total study sample consisted of 7052 patients with diabetes across 68 providers at 20 selected primary care offices. The design included 2 stages: First, primary care practices were randomly assigned to have their providers receive education regarding blood glucose flowsheet orders. Then, patients in the treated practices were assigned to 1 of 4 reminder interventions. RESULTS: Provider education successfully increased provider take-up of an online blood glucose monitoring tool by 64 percentage points, while a comparison of reminder interventions revealed that emphasizing accountability to the provider encouraged patients to track their blood glucose online. An assessment of downstream outcomes revealed impacts of the interventions on prescribing behavior and A1c testing frequency. DISCUSSION: It is important to understand how health systems can practically promote take-up and awareness of emerging digital health alternatives or those with persistently low utilization in clinical settings. CONCLUSION: These results indicate that provider training and support are critical first steps to promote utilization of patient-generated health data, and that patient communications can provide further motivation.

Prenatal internalizing symptoms as a mediator linking maternal adverse childhood experiences with infant temperament.

BACKGROUND: Maternal adverse childhood experiences are known to significantly influence offspring development. However, mediators linking maternal early-life adversity with infant temperament remain largely unknown. AIMS: The current study investigated whether prenatal internalizing symptoms mediate the association between maternal adverse childhood experiences and infant temperament at two months. Maternal sensitivity/responsiveness during the postpartum period was also examined as a moderator of these associations. STUDY DESIGN: We used a repeated-measures design, with self-report measures administered during pregnancy. Self-report and observational data were also collected at 2 months postpartum. SUBJECTS: The study included a community sample of 64 pregnant women and their infants. OUTCOME MEASURES: Participants completed measures assessing their early-life adversity and current depression/anxiety symptoms. At two months postpartum, mothers reported on their infant's temperament and participated in a parent-child interaction task designed to assess maternal sensitivity/responsiveness. RESULTS AND CONCLUSIONS: Maternal adverse childhood experiences indirectly predicted poor self-regulation during early infancy via prenatal internalizing symptoms. Maternal sensitivity/responsiveness was also found to moderate the association between maternal adverse childhood experiences and certain aspects of infant regulatory capacity and positive affectivity at two months. This research has implications for mental health screening procedures during pregnancy and the development of early intervention programs.

Anti-amphiphysin positive stiff-person syndrome due to invasive ductal carcinoma in a male patient.

Stiff-person syndrome (SPS) is a rare progressive neurological disorder characterised by painful muscle spasms and progressive muscle rigidity, leading in some cases to impaired ambulation. Anti-amphiphysin positive SPS is a paraneoplastic variant, frequently associated with breast carcinomas and small cell lung cancers. We report the case of a 53-year-old patient who developed symptoms of anti-amphiphysin positive SPS 3 years before being diagnosed with invasive ductal carcinoma. Specifically, computed tomography (CT) of the chest, abdomen and pelvis, positron emission tomography-CT (PET-CT), mammogram, colonoscopy and magnetic resonance imaging (MRI) did not identify malignancy during the 3 years following the onset of symptoms. Following diagnosis of invasive ductal carcinoma and completion of curative-intent oncological treatment, the patient experienced improvement, though not complete resolution, in his SPS symptoms. This case highlights the importance of thorough oncological workup when clinical presentation and diagnostic testing are suggestive of anti-amphiphysin positive SPS.

Association of provider advice and gestational weight gain in twin pregnancies: a cross-sectional electronic survey.

BACKGROUND: Little is known about patient-provider communication on gestational weight gain among women pregnant with twins, a growing population at high risk for adverse maternal and neonatal outcomes. We examined if women's report of provider advice on gestational weight gain was consistent with the Institute of Medicine (IOM) weight gain guidelines for twin pregnancies, and the association of provider advice on weight gain with women's weight gain during their twin pregnancy. METHODS: We conducted a cross-sectional survey of 276 women who delivered twins and received prenatal care in the United States. The 2009 IOM provisional weight gain guidelines for twin pregnancies defined whether provider advice on weight gain and women's weight gain were below, within, or above guidelines. Multinomial logistic regression examined associations between provider advice on weight gain with women's weight gain, after adjustment for maternal age, gestational age at delivery, education, parity, twin type, use of assisted reproductive technologies and pre-pregnancy BMI category. RESULTS: Approximately 30% of women described provider advice on weight gain below the IOM guidelines, 60% within, and 10% above guidelines. Compared to women who reported weight gain advice within guidelines, women who reported advice below guidelines or who reported no advice were 7.1 (95% CI: 3.2, 16.0) and 2.7 (95% CI: 1.3, 5.6) times more likely to gain less than recommended, respectively. Women who reported provider advice above guidelines were 4.6 (95% CI: 1.5, 14.2) times more likely to exceed guidelines. CONCLUSIONS: Provider advice on gestational weight gain may be an important predictor of women's weight gain during twin pregnancies, highlighting the critical need for accurate provider counseling to optimize health outcomes.

Validity of self-reported and objectively measured sedentary behavior in pregnancy.

BACKGROUND: Sedentary behavior (SED) is a potential risk factor for poor pregnancy outcomes. We evaluated the validity of several common and one new method to assess SED across three trimesters of pregnancy. METHODS: This cohort study of pregnant women measured objective and self-reported SED each trimester via thigh-worn activPAL3 micro (criterion), waist-worn Actigraph GT3X, and self-report from the Pregnancy Physical Activity Questionnaire (PPAQ) and the de novo Sedentary Behavior Two Domain Questionnaire (SB2D). SED (hours per day) and percent time in SED (SED%) from activPAL were compared to GT3X, SB2D, and PPAQ using Pearson's r, ICC, Bland-Altman analysis, and comparison of criterion SED and SED% across tertiles of alternative methods. RESULTS: Fifty-eight women (mean age 31.5 ± 4.8 years; pre-pregnancy BMI 25.1 ± 5.6 kg/m2; 76% white) provided three trimesters of valid activPAL data. Compared to activPAL, GT3X had agreement ranging from r = 0.54-0.66 and ICC = 0.52-0.65. Bland-Altman plots revealed small mean differences and unpatterned errors, but wide limits of agreement (greater than ±2 h and ± 15%). The SB2D and PPAQ had r < 0.5 and ICC < 0.3 vs. activPAL SED, with lower agreement during the 2nd and 3rd trimesters, and performed poorly in Bland-Altman analyses. SED% from the modified SB2D performed best of the self-reported instruments with modest mean differences, r ranging from 0.55 to 0.60, and ICCs from 0.31-0.33; though, limits of agreement were greater than ±35%. Significant trends in activPAL SED were observed across increasing tertiles of SB2D SED in the 1st and 3rd trimesters (both p ≤ 0.001), but not the 2nd trimester (p = 0.425); and for PPAQ SED in the 1st and 2nd trimesters (both p < 0.05), but not the 3rd trimester (p = 0.158). AcitvPAL SED and SED% increased significantly across tertiles of GT3X SED and SED% as well as SB2D SED% (all p-for-trend ≤ 0.001). CONCLUSIONS: Compared to activPAL, waist-worn GT3X produced moderate agreement, though similar mean estimates of SED across pregnancy. Self-report questionnaires had large absolute error and wide limits of agreement for SED hr./day; SB2D measurement of SED% was the best self-report method. These data suggest activPAL be used to measure SED when possible, followed by GT3X, and - when necessary - SB2D assessing SED% in pregnancy. TRIAL REGISTRATION: www.clinicaltrials.gov NCT03084302 on 3/20/2017.

An analysis of postpartum walking balance and the correlations to anthropometry.

BACKGROUND: Falls caused by balance issues during pregnancy are quite common, and these issues can continue postpartum, potentially posing a danger to both the mother and baby. While there has been research on changes to walking gait during pregnancy, walking balance in the postpartum period has yet to be examined. Therefore, the aims of this study were to examine if balance changes persist in postpartum and the contribution of anthropometry changes. METHODS: This was done through longitudinal observational cohort study at 16 and 40 weeks gestation and at four-week intervals postpartum. Balance was measured as lateral center of mass motion during treadmill walking, and recorded with motion capture cameras following anthropometric measurements. Balance variables were statistically analyzed to observe how they changed over time. Hierarchical regression analyses determined correlations between balance and anthropometry. RESULTS: Balance was observed to improve significantly just following birth. Additionally, there were changes that continued to indicate improvement throughout the postpartum period. Anthropometry changes were significantly, but minimally, correlated with balance changes. SIGNIFICANCE: Many women begin to return to normal activities soon after birth. With women participating in various forms of exercise, potentially rigorous work requirements, and tasks around the home, it is important that they, their medical providers, and employers understand and consider the continued risks of imbalance.

Provider advice on physical activity and nutrition in twin pregnancies: a cross-sectional electronic survey.

BACKGROUND: Health care providers should counsel pregnant patients on physical activity and nutrition to improve pregnancy outcomes. However, little is known about provider advice on these lifestyle behaviors among women pregnant with twins, a growing population at high risk for pregnancy complications. We examined the prevalence and content of provider advice on physical activity and nutrition among women pregnant with twins. METHODS: A cross-sectional electronic survey was administered to 276 women who delivered twins in the past 3 years and received prenatal care in the United States. The proportion of women reporting provider advice on physical activity and nutrition during prenatal visits (yes/no) was assessed and open-ended questions examined the content of provider advice. Bivariate differences in participant characteristics, stratified by provider advice on physical activity and nutrition (yes/no), were assessed. Responses from open-ended questions were examined using a content analysis approach to identify commonly reported advice on physical activity and nutrition. RESULTS: Approximately 75 and 63% of women reported provider advice on physical activity and nutrition, respectively, during their twin pregnancy. Women who recalled advice on physical activity most commonly reported recommendations to walk at a light to moderate intensity level. However, few women reported physical activity recommendations consistent with current guidelines, and approximately 55% of women reported provider advice to limit or restrict activity during their pregnancy, including bedrest. Nutrition advice was focused on eating a healthy, balanced diet and increasing protein intake. More women reported self-initiating the conversation on physical activity with their provider (40%) compared to nutrition (21%). Despite limited advice, 70% of women reported being satisfied or very satisfied with the information they received from their provider on physical activity or nutrition. CONCLUSIONS: The majority of women reported provider advice on physical activity and nutrition during their twin pregnancies. However, advice was limited in detail, and physical activity levels were commonly restricted, despite the lack of evidence that activity restriction is beneficial during pregnancy. More research is needed to determine the optimal physical activity and dietary patterns in twin pregnancies to facilitate clear and consistent provider counseling on these lifestyle behaviors.

Walking for health during pregnancy: A literature review and considerations for future research.

Walking is the most commonly chosen type of physical activity (PA) during pregnancy and provides several health benefits to both mother and child. National initiatives have promoted the importance of walking in general, but little emphasis is directed toward pregnant women, the majority of whom are insufficiently active. Pregnant women face a variety of dynamic barriers to a physically active lifestyle, some of which are more commonly experienced during specific times throughout the pregnancy experience. Walking is unique in that it appears resistant to a number of these barriers that limit other types of PA participation, and it can be meaningfully integrated into some transportation and occupational activities when leisure-time options are unavailable. Preliminary intervention work suggests that walking programs can be effectively adopted into a typical pregnancy lifestyle. However, a great deal of work remains to administer successful pregnancy walking interventions, including developing and using validated methods of PA and walking assessment. This narrative review discusses the unique advantages of walking during pregnancy, provides recommendations for future intervention work, and outlines the need for pregnancy-focused community walking initiatives. Standard search procedures were followed to determine sources from the literature specific to walking during pregnancy for use in each section of this review.

Associations Among Work-Related and Leisure-Time Physical Activity With Level of Nausea During Pregnancy.

OBJECTIVE: Pregnancy-induced nausea and vomiting are common maladies during early pregnancy and may be related to physical activity (PA). Our objective was to determine relations among work-related PA (work PA), leisure-time physical activity (LTPA), and nausea during the first trimester. STUDY DESIGN: Online or mailed surveys with questions on pregnancy-related nausea, work PA, and LTPA were completed by 70 women at 15 to 30 months postpartum. Women recalled nausea during the first trimester (none, ≤1 h/d, 2-3 h/d, 4-6 h/d, ≥6 h/d) as well as LTPA frequency, duration, and type. Women also recalled total working hours in their first trimester and percentage of time sitting, standing, and walking at work. RESULTS: A total of 42 women (60%) were categorized as having high nausea (≥2 h/d). Mann-Whitney U tests showed that women with low nausea had significantly more MET minutes per week of LTPA (P = .05) and hours per week spent standing at work (P = .03). Logistic regression analyses showed standing for ≥20 h/wk at work was related to reduced odds of high nausea (adjusted odds ratio = 0.23; 95% CI = 0.06-0.96), whereas meeting LTPA guidelines was nonsignificantly related to reduced odds. CONCLUSION: These findings suggest an inverse relationship between first trimester PA and level of nausea. Further investigation is needed to determine the directionality of these relations.

Describing the sternalis muscle: a new variant and an amended classification.

PURPOSE: With emphasis on the clinical setting, knowledge of anatomical variation decreases misdiagnoses and surgical complications. We report a previously undocumented variant of sternalis muscle and recommend an augmented classification scheme. METHODS: Dissection of the anterior thoracic wall on an 83-year-old female cadaver revealed bilateral sternalis muscles. The Snosek et al. classification system was referenced to describe the variant types. RESULTS: The right sternalis muscle has a single belly and can be classified using the Snosek et al. classification system as a simple type, right single. The left sternalis muscle presented with three muscle bellies, each having a unique pattern of superior attachments (heads). This variation is previously undocumented and requires a more detailed classification. CONCLUSIONS: We propose the addition of a new subtype of sternalis classification, as well as a modification to the Snosek et al. (Clin Anat 27:866-884, 2014) classification scheme, to include classification of different muscle bellies when multiple are present.

Walking balance on a treadmill changes during pregnancy.

BACKGROUND: Altered standing balance during pregnancy has been previously reported. To date, body center of mass (bCOM) motion has not been used to track balance changes in this population. We recently compared three methods to determine the torso center of mass (tCOM) location (via force plate acquired center of pressure calculation, using Pavol surface anthropometry measurements, and a combination of the two) to use in calculating the bCOM during pregnancy. RESEARCH QUESTION: This current research explored two questions: (1) does walking balance change during pregnancy, and (2) do the methods for identifying tCOM location affect the resulting balance measures? METHODS: Fifteen pregnant women were recruited to perform 60-second trial of treadmill walking at 4-week intervals from 12 weeks gestation until delivery. Walking balance was measured as bCOM motion within the base of support. Gestation time and anthropometric model (force plate, Pavol, and combination) were repeated-measures independent variables in a general linear mixed model analysis. RESULTS: There was a significant decrease in walking balance during pregnancy. As gestation progressed, we observed non-linear changes in the bCOM motion within the base of support over time, with some changes starting early in pregnancy and others not starting until late 2nd trimester. The anthropometric model used to locate the bCOM significantly influences balance measures. The results of this study indicate that the force plate method is more appropriate for locating the tCOM in the anterior and lateral directions. SIGNIFICANCE: The results of this study will inform clinicians and patients about the gestational stage-associated changes in balance during pregnancy that increase the risk of falling and injury. Researchers should also carefully consider the method for locating the bCOM.

Changes in collegiate ice hockey player anthropometrics and aerobic fitness over 3 decades.

Over the past several decades, an increased emphasis on fitness training has emerged among collegiate ice hockey teams, with the objective of improving on-ice performance. However, it is unknown if this increase in training has translated over time into changes in the anthropometric and fitness profiles of collegiate ice hockey players. The purposes of this study were to describe anthropometric (height, weight, body mass index (BMI), percent body fat (%fat)) and aerobic fitness (peak oxygen consumption) characteristics of collegiate ice hockey players over a period of 36 years and to evaluate whether these characteristics differ among player positions. Anthropometric and physiologic data were obtained through preseason fitness testing of players (N = 279) from a National Collegiate Athletic Association Division I men's ice hockey team from the years 1980 through 2015. Changes over time in the anthropometric and physiologic variables were evaluated via regression analysis using linear and polynomial models, and differences among player positions were compared via ANOVA (p < 0.05). Regression analysis revealed that a cubic model best predicted changes in mean height (R2 = 0.65), weight (R2 = 0.77), and BMI (R2 = 0.57), whereas a quadratic model best fit change in %fat by year (R2 = 0.30). Little change was observed over time in the anthropometric characteristics. Defensemen were significantly taller than forwards (184.7 ± 12.1 vs. 181.3 ± 5.9 cm) (p = 0.007), and forwards had a higher relative peak oxygen consumption compared with defensemen (58.7 ± 4.7 vs. 57.2 ± 4.4 mL·kg-1·min-1) (p = 0.032). No significant differences were observed in %fat or weight by position. Although average player heights and weights fluctuated over time, increased emphasis on fitness training did not affect the athletes' relative aerobic fitness. Differences in height and aerobic fitness levels were observed among player positions.

A comparison of methods to determine center of mass during pregnancy.

Balance changes during pregnancy likely occur because of mass gains and mass distribution changes. However, to date there is no way of tracking balance through center of mass motion because no method is available to identify of the body center of mass throughout pregnancy. We compared methods for determining segment masses and torso center of mass location. The availability of a method for tracking these changes during pregnancy will make determining balance changes through center of mass motion an option for future pregnancy balance research. Thirty pregnant women from eight weeks gestation until birth were recruited for monthly anthropometric measurements, motion capture analysis of body segment locations, and force plate analysis of center of pressure during quiet standing and supine laying. From these measurements, we were able to compare regression, volume measurement, and weighted sum methods to calculate body center of mass throughout pregnancy. We found that mass changes around the trunk were most prevalent as expected, but mass changes throughout the body (especially the thighs) were also seen. Our findings also suggest that a series of anthropometric measurements first suggested by Pavol et al. (2002), in combination with quiet standing on a force plate, can be used to identify the needed components (segment masses and torso center of mass location in three dimensions) to calculate body center of mass changes during pregnancy. The results of this study will make tracking of center of mass motion a possibility for future pregnancy balance research.

Neuronal networks provide rapid neuroprotection against spreading toxicity.

Acute secondary neuronal cell death, as seen in neurodegenerative disease, cerebral ischemia (stroke) and traumatic brain injury (TBI), drives spreading neurotoxicity into surrounding, undamaged, brain areas. This spreading toxicity occurs via two mechanisms, synaptic toxicity through hyperactivity, and excitotoxicity following the accumulation of extracellular glutamate. To date, there are no fast-acting therapeutic tools capable of terminating secondary spreading toxicity within a time frame relevant to the emergency treatment of stroke or TBI patients. Here, using hippocampal neurons (DIV 15-20) cultured in microfluidic devices in order to deliver a localized excitotoxic insult, we replicate secondary spreading toxicity and demonstrate that this process is driven by GluN2B receptors. In addition to the modeling of spreading toxicity, this approach has uncovered a previously unknown, fast acting, GluN2A-dependent neuroprotective signaling mechanism. This mechanism utilizes the innate capacity of surrounding neuronal networks to provide protection against both forms of spreading neuronal toxicity, synaptic hyperactivity and direct glutamate excitotoxicity. Importantly, network neuroprotection against spreading toxicity can be effectively stimulated after an excitotoxic insult has been delivered, and may identify a new therapeutic window to limit brain damage.