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OBJECTIVE: Bradykinesia is the major cardinal motor sign of Parkinson disease (PD), but its neural underpinnings are unclear. The goal of this study was to examine whether changes in bradykinesia following long-term subthalamic nucleus (STN) deep brain stimulation (DBS) are linked to local STN beta (13-30 Hz) dynamics or a wider bilateral network dysfunction. METHODS: Twenty-one individuals with PD implanted with sensing neurostimulators (Activa® PC + S, Medtronic, PLC) in the STN participated in a longitudinal 'washout' therapy study every three to 6 months for an average of 3 years. At each visit, participants were withdrawn from medication (12/24/48 hours) and had DBS turned off (>60 minutes) before completing a repetitive wrist-flexion extension task, a validated quantitative assessment of bradykinesia, while local field potentials were recorded. Local STN beta dynamics were investigated via beta power and burst duration, while interhemispheric beta synchrony was assessed with STN-STN beta coherence. RESULTS: Higher interhemispheric STN beta coherence, but not contralateral beta power or burst duration, was significantly associated with worse bradykinesia. Bradykinesia worsened off therapy over time. Interhemispheric STN-STN beta coherence also increased over time, whereas beta power and burst duration remained stable. The observed change in bradykinesia was related to the change in interhemispheric beta coherence, with greater increases in synchrony associated with further worsening of bradykinesia. INTERPRETATION: Together, these findings implicate interhemispheric beta synchrony as a neural correlate of the progression of bradykinesia following chronic STN DBS. This could imply the existence of a pathological bilateral network contributing to bradykinesia in PD. ANN NEUROL 2023;93:1029-1039.
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Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Hipocinesia/complicações , Estimulação Encefálica Profunda/efeitos adversos , Doença de Parkinson/terapia , Doença de Parkinson/tratamento farmacológico , Núcleo Subtalâmico/fisiologiaRESUMO
Food insecurity is highly prevalent and linked to poorer diet and worse metabolic outcomes. Food insecurity can be stressful, and could elicit chronic psychological and physiological stress. In this study, we tested whether stress could be used to identify those at highest risk for worse diet and metabolic measures from food insecurity. Specifically, we hypothesized that cortisol (a physiological marker of stress) and perceived psychological stress would amplify the link between food insecurity and hyperpalatable food intake as well as metabolic measures. In a sample of 624 Black and White women aged 36-43 who participated in the NHLBI Growth and Health Study's midlife assessment, we assessed associations between food insecurity with hyperpalatable food intake (high fat + high sodium foods; high fat + high sugar foods; and high carbohydrate + high sodium foods), and metabolic measures (fasting glucose, insulin resistance, and waist circumference). We found that food insecurity was associated with higher levels of perceived stress (R2 = 0.09), and greater intake of high fat + high sugar (hyperpalatable) foods (R2 = 0.03). In those with higher cumulative cortisol (as indexed by hair cortisol), food insecurity was associated with higher levels of fasting glucose. Neither cortisol nor perceived stress moderated any other relationships, and neither variable functioned as a mediator in sensitivity analyses. Given these largely null findings, further research is needed to understand the role stress plays in the chronic health burdens of food insecurity.
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Abastecimento de Alimentos , Hidrocortisona , Humanos , Feminino , Hidrocortisona/metabolismo , Dieta , Insegurança Alimentar , Glucose , Açúcares , Sódio , Estresse Psicológico/psicologiaRESUMO
BACKGROUND: Although maternal stressor exposure has been associated with shorter telomere length (TL) in offspring, this literature is based largely on White samples. Furthermore, timing of maternal stressors has rarely been examined. Here, we examined how maternal stressors occurring during adolescence, pregnancy, and across the lifespan related to child TL in Black and White mothers. METHOD: Mothers (112 Black; 110 White; Mage = 39) and their youngest offspring (n = 222; Mage = 8) were part of a larger prospective cohort study, wherein mothers reported their stressors during adolescence (assessed twice during adolescence for the past year), pregnancy (assessed in midlife for most recent pregnancy), and across their lifespan (assessed in midlife). Mother and child provided saliva for TL measurement. Multiple linear regression models examined the interaction of maternal stressor exposure and race in relation to child TL, controlling for maternal TL and child gender and age. Race-stratified analyses were also conducted. RESULTS: Neither maternal adolescence nor lifespan stressors interacted with race in relation to child TL. In contrast, greater maternal pregnancy stressors were associated with shorter child TL, but this effect was present for children of White but not Black mothers. Moreover, this effect was significant for financial but not social pregnancy stressors. Race-stratified models revealed that greater financial pregnancy stressors predicted shorter telomeres in offspring of White, but not Black mothers. CONCLUSIONS: Race and maternal stressors interact and are related to biological aging across generations, but these effects are specific to certain races, stressors, and exposure time periods.
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Mães , Encurtamento do Telômero , Adolescente , Adulto , Criança , Feminino , Humanos , Gravidez , Exposição Materna , Mães/psicologia , Estudos Prospectivos , Telômero/fisiologia , Encurtamento do Telômero/fisiologia , População Branca/psicologia , Relação entre Gerações/etnologia , Negro ou Afro-Americano/psicologia , Adulto Jovem , Pessoa de Meia-IdadeRESUMO
Low-income Black and Latinx individuals are disproportionately vulnerable to chronic stress and metabolic disease. Evidence suggests that these populations engage in elevated levels of comfort eating (i.e., eating comforting food to alleviate stress), which can harm diet quality. For this reason, many interventions discourage comfort eating. However, if comfort eating does indeed buffer stress, it may be a protective health behavior, particularly if healthy foods (e.g., strawberries) buffer stress as effectively as traditional unhealthy comfort foods (e.g., brownies). By choosing healthy foods, people may be able to simultaneously improve their nutrition and reduce their stress levels, both of which have the potential to reduce health disparities among chronically stressed populations. The present study tested the efficacy of healthy and unhealthy comfort eating for improving psychophysiological stress recovery. A sample of low-income Black and Latinx individuals (N = 129) were randomly assigned to consume a healthy food (e.g., grapes), unhealthy comfort food (e.g., chips), or no food after exposure to a laboratory stressor. Throughout, we measured participants' psychophysiological stress responses, including self-reported stress, rumination, autonomic nervous system activation (i.e., electrodermal activity (EDA), heart rate variability (HRV)) and neuroendocrine responses (i.e., salivary cortisol). We compared participants' stress recovery trajectories by condition and found no significant group differences (p = 0.12 for self-reported stress; p = 0.92 for EDA; p = 0.22 for HRV, p = 1.00 for cortisol). Participants in all conditions showed decreases in self-reported stress and in cortisol post-stressor (ps < 0.01), but rates of decline did not differ by condition (i.e., healthy or unhealthy comfort food, brief no-food waiting period). Although null, these results are important because they challenge the widely-held assumption that comfort foods help people decrease stress.
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Dieta , Hidrocortisona , Adulto , Ingestão de Alimentos , Comportamento Alimentar , Alimentos , Preferências Alimentares , Comportamentos Relacionados com a Saúde , HumanosRESUMO
Parkinson's disease (PD) is a systemic brain disorder where the cortical cholinergic network begins to degenerate early in the disease process. Readily accessible, quantitative, and specific behavioral markers of the cortical cholinergic network are lacking. Although degeneration of the dopaminergic network may be responsible for deficits in cardinal motor signs, the control of gait is a complex process and control of higher-order aspects of gait, such as gait variability, may be influenced by cognitive processes attributed to cholinergic networks. We investigated whether swing time variability, a metric of gait variability that is independent from gait speed, was a quantitative behavioral marker of cortical cholinergic network integrity in PD. Twenty-two individuals with PD and subthalamic nucleus (STN) deep brain stimulation (PD-DBS cohort) and twenty-nine age-matched controls performed a validated stepping-in-place (SIP) task to assess swing time variability off all therapy. The PD-DBS cohort underwent structural MRI scans to measure gray matter volume of the Nucleus Basalis of Meynert (NBM), the key node in the cortical cholinergic network. In order to determine the role of the dopaminergic system on swing time variability, it was measured ON and OFF STN DBS in the PD-DBS cohort, and on and off dopaminergic medication in a second PD cohort of thirty-two individuals (PD-med). A subset of eleven individuals in the PD-DBS cohort completed the SIP task again off all therapy after three years of continuous DBS to assess progression of gait impairment. Swing time variability was significantly greater (i.e., worse) in PD compared to controls and greater swing time variability was related to greater atrophy of the NBM, as was gait speed. STN DBS significantly improved cardinal motor signs and gait speed but did not improve swing time variability, which was replicated in the second cohort using dopaminergic medication. Swing time variability continued to worsen in PD, off therapy, after three years of continuous STN DBS, and NBM atrophy showed a trend for predicting the degree of increase. In contrast, cardinal motor signs did not progress. These results demonstrate that swing time variability is a reliable marker of cortical cholinergic health, and support a framework in which higher-order aspects of gait control in PD are reliant on the cortical cholinergic system, in contrast to other motor aspects of PD that rely on the dopaminergic network.
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Atrofia/fisiopatologia , Transtornos Neurológicos da Marcha/fisiopatologia , Marcha/fisiologia , Doença de Parkinson/fisiopatologia , Núcleo Subtalâmico/fisiopatologia , Idoso , Atrofia/patologia , Núcleo Basal de Meynert/fisiopatologia , Estimulação Encefálica Profunda/métodos , Feminino , Transtornos Neurológicos da Marcha/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiologiaRESUMO
BACKGROUND: Young plasma infusions have emerged as a potential treatment for neurodegenerative disease, and convalescent plasma therapy has been used safely in the management of viral pandemics. However, the effect of plasma therapy in Parkinson's disease (PD) is unknown. OBJECTIVES: The objective of this study was to determine the safety, tolerability, and feasibility of plasma infusions in people with PD. METHODS: A total of 15 people with clinically established PD, at least 1 cognitive complaint, and on stable therapy received 1 unit of young fresh frozen plasma twice a week for 4 weeks. Assessments and adverse effects were performed/reported on and off therapy at baseline, immediately after, and 4 weeks after the infusions ended. Adverse effects were also assessed during infusions. The primary outcomes were safety, tolerability, and feasibility. Exploratory outcomes included Unified Parkinson's Disease Rating Scale Part III off medication, neuropsychological battery, Parkinson's Disease Questionnaire-39, inflammatory markers (tumor necrosis factor-α, interleukin-6), uric acid, and quantitative kinematics. RESULTS: Adherence rate was 100% with no serious adverse effects. There was evidence of improvement in phonemic fluency (P = 0.002) and in the Parkinson's Disease Questionnaire-39 stigma subscore (P = 0.013) that were maintained at the delayed evaluation. Elevated baseline tumor necrosis factor-α levels decreased 4 weeks after the infusions ended. CONCLUSIONS: Young fresh frozen plasma was safe, feasible, and well tolerated in people with PD, without serious adverse effects and with preliminary evidence for improvements in phonemic fluency and stigma. The results of this study warrant further therapeutic investigations in PD and provide safety and feasibility data for plasma therapy in people with PD who may be at higher risk for severe complications of COVID-19. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Transfusão de Componentes Sanguíneos/efeitos adversos , Doença de Parkinson/terapia , Plasma , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Antiparkinsonianos/uso terapêutico , Fenômenos Biomecânicos , COVID-19/epidemiologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/terapia , Terapia Combinada , Estimulação Encefálica Profunda , Estudos de Viabilidade , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/sangue , Doença de Parkinson/psicologia , Risco , Índice de Gravidade de Doença , Distúrbios da Fala/etiologia , Distúrbios da Fala/terapia , Fator de Necrose Tumoral alfa/sangueRESUMO
OBJECTIVE: Although emerging studies examine the inverse relationship between body satisfaction and disordered eating for Black women, it has not been established how racially salient aspects of body satisfaction may have implications for eating behaviors and longitudinal health outcomes. METHOD: In a longitudinal sample of 455 Black women, we examined whether skin color satisfaction across ages 10-15 was directly related to adult health outcomes at age 40 (e.g., disordered eating, self-esteem, self-reported health, depressive symptoms, and cardiovascular risk). We also investigated the indirect impact of skin color satisfaction on adult health, mediated by body satisfaction, and binge eating. RESULTS: No significant direct or indirect effects of adolescent skin color satisfaction were observed for depressive symptoms or cardiovascular health outcomes. At ages 10 and 12, skin color satisfaction had negative and positive direct effects, respectively, on self-esteem. At age 15, greater skin color satisfaction was directly associated with greater self-reported health. Post hoc analyses revealed that when additionally accounting for adolescent body satisfaction, greater skin color satisfaction was indirectly associated with greater self-esteem and self-reported health, alongside lower cardiovascular risk. CONCLUSIONS: Although previous research suggests that in adolescence, Black girls' skin color satisfaction affects both body satisfaction and disordered eating behaviors, this association does not hold into midlife. Rather, post hoc analyses suggest that the lasting effects of adolescent skin color satisfaction are mediated by the longitudinal stability of body satisfaction, which in turn, is associated with adult health outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Bulimia , Transtornos da Alimentação e da Ingestão de Alimentos , Adulto , Humanos , Feminino , Adolescente , Pigmentação da Pele , Autoimagem , Bulimia/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Satisfação Pessoal , Avaliação de Resultados em Cuidados de Saúde , Imagem Corporal/psicologiaRESUMO
Although the association between objective markers of low socioeconomic status (SES) and poor health is well established, one underexamined possibility is that over and above objective SES, social class stigma-experiences and anticipation of discrimination based on social class-might undermine people's ability to engage in healthy behaviors. Participants (N = 2022) were recruited between December 2019 and January 2020 via a national Qualtrics panel that was census-matched to the U.S. population in age, gender, income, race/ethnicity, and census region. Participants completed measures of class stigma, alcohol use, disordered eating, comfort eating, sleep disturbance, physical activity, and demographics. Controlling for objective SES and demographics, generalized linear regression models indicated that class stigma was associated with significantly greater alcohol use, disordered eating, greater comfort eating, and sleep disturbance but not less physical activity. Class stigma was not associated with health behaviors after full adjustment for weight/racial discrimination and psychological factors. Results from this investigation suggest that beyond one's objective SES, the stigma associated with having low class may also contribute to poorer health behaviors.
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Transtornos da Alimentação e da Ingestão de Alimentos , Estigma Social , Humanos , Classe Social , Etnicidade , Comportamentos Relacionados com a SaúdeRESUMO
BACKGROUND: Early vascular ageing (EVA) contributes to elevated risk of cardiovascular disease (CVD), which disproportionately affects African American women. Incarceration, an event disproportionately impacting African Americans, may be a stressor contributing to EVA in African American women. Further, the subjective perspective, commonly referred to as appraisal, of incarceration may also be important for health. We hypothesised that having family and/or friends incarcerated and appraising the incarceration as upsetting would be associated with indices of EVA. METHODS: In a community-based cohort of African American women aged 30-46 living in Atlanta, Georgia (n=391), participants were asked, at baseline, about family and/or friend incarceration and to appraise how upsetting the incarceration was. Multivariable linear regression examined associations between: (1) family and/or friend incarceration and indices of EVA (pulse wave velocity, augmentation index, central systolic blood pressure (SBP) and pulse pressure amplification) and (2) appraisal of incarceration and EVA indices. RESULTS: 45% of participants (n=174) reported having a loved one incarcerated, and 59% (n=102) reported the incarceration as upsetting. Having a loved one incarcerated was associated with a higher central SBP (b=4.30; 95% CI 1.61, 6.99) and augmentation index (b=2.29; 95% CI 0.26, 4.33). Appraisal of incarceration was only associated with central SBP. CONCLUSIONS: Family or friend incarceration was highly prevalent in this cohort of African American women and associated with indices of EVA. Mass incarceration of others may affect the physical health of African American women which may contribute to CVD disparities.
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The purpose of the current study was to test the longitudinal association between disordered eating symptoms (body dissatisfaction, drive for thinness and bulimia) in adolescence (ages 12, 14, 16, 18, 19) and adulthood (age 40) in a sample of 883 white and Black women. We also investigated moderation by race. Adolescent symptoms at each time point significantly predicted adulthood symptoms for the body dissatisfaction and drive for thinness subscales, for both Black and white women. Bulimia symptoms in adolescence predicted symptoms in adulthood; however, the effect was largely driven by white women. Although moderation was non-significant, among white women, bulimia symptoms at all adolescent time points predicted adulthood bulimia, but among Black women, only symptoms at ages 18 and 19 were predictive of adulthood bulimia. Results suggest that both Black and white women are susceptible to disordered eating and that symptoms emerging in adolescence can potentially follow women into midlife.
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Although it has been demonstrated that (a) body dissatisfaction and internalization of societal appearance standards contribute to disordered eating and (b) that internalization of societal appearance standards leads to decreased skin color satisfaction among Black women, it has not been established whether skin color dissatisfaction contributes to disordered eating among Black women or girls. The objective of the present study is to determine the influence of skin color satisfaction as a potential predictor for binge eating, and its effect through body image in Black girls during the vulnerable developmental period of adolescence. Using data from ten annual measurements in 1213 Black girls across ages 10-19, we sought to determine whether skin color satisfaction predicts Binge Eating Disorder (BED) risk and symptoms using pre-registered logistic and multilevel models. We found that lower skin color satisfaction at ages 13 and 14 significantly predicted greater odds of BED and lower skin color satisfaction at all ages predicted greater BED symptoms. Body satisfaction mediated the relationship between skin color satisfaction and BED symptoms. Our results suggest that skin color dissatisfaction is a novel component of body image for Black girls that is also related to binge eating.
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Transtorno da Compulsão Alimentar , Bulimia , Transtornos da Alimentação e da Ingestão de Alimentos , Adolescente , Adulto , Imagem Corporal/psicologia , Criança , Feminino , Humanos , Satisfação Pessoal , Estudos Prospectivos , Pigmentação da Pele , Adulto JovemRESUMO
Background: Resting state beta band (13-30 Hz) oscillations represent pathological neural activity in Parkinson's disease (PD). It is unknown how the peak frequency or dynamics of beta oscillations may change among fine, limb, and axial movements and different disease phenotypes. This will be critical for the development of personalized closed loop deep brain stimulation (DBS) algorithms during different activity states. Methods: Subthalamic (STN) and local field potentials (LFPs) were recorded from a sensing neurostimulator (Activa® PC + S, Medtronic PLC.) in fourteen PD participants (six tremor-dominant and eight akinetic-rigid) off medication/off STN DBS during 30 s of repetitive alternating finger tapping, wrist-flexion extension, stepping in place, and free walking. Beta power peaks and beta burst dynamics were identified by custom algorithms and were compared among movement tasks and between tremor-dominant and akinetic-rigid groups. Results: Beta power peaks were evident during fine, limb, and axial movements in 98% of movement trials; the peak frequencies were similar during each type of movement. Burst power and duration were significantly larger in the high beta band, but not in the low beta band, in the akinetic-rigid group compared to the tremor-dominant group. Conclusion: The conservation of beta peak frequency during different activity states supports the feasibility of patient-specific closed loop DBS algorithms driven by the dynamics of the same beta band during different activities. Akinetic-rigid participants had greater power and longer burst durations in the high beta band than tremor-dominant participants during movement, which may relate to the difference in underlying pathophysiology between phenotypes.
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OBJECTIVE: To investigate the progression of neural and motor features of Parkinson's disease in a longitudinal study, after washout of medication and bilateral subthalamic nucleus deep brain stimulation (STN DBS). METHODS: Participants with clinically established Parkinson's disease underwent bilateral implantation of DBS leads (18 participants, 13 male) within the STN using standard functional frameless stereotactic technique and multi-pass microelectrode recording. Both DBS leads were connected to an implanted investigative sensing neurostimulator (Activa™ PC + S, Medtronic, PLC). Resting state STN local field potentials (LFPs) were recorded and motor disability, (the Movement Disorder Society-Unified Parkinson's Disease Rating Scale - motor subscale, MDS-UPDRS III) was assessed off therapy at initial programming, and after 6 months, 1 year, and yearly out to 5 years of treatment. The primary endpoint was measured at 3 years. At each visit, medication had been held for over 12/24 h and DBS was turned off for at least 60 min, by which time LFP spectra reached a steady state. RESULTS: After 3 years of chronic DBS, there were no increases in STN beta band dynamics (p = 0.98) but there were increases in alpha band dynamics (p = 0.0027, 25 STNs). Similar results were observed in a smaller cohort out to 5 years. There was no increase in the MDS-UPDRS III score. INTERPRETATION: These findings provide evidence that the beta oscillopathy does not substantially progress following combined STN DBS plus medication in moderate to advanced Parkinson's disease.
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Ritmo beta/fisiologia , Estimulação Encefálica Profunda , Progressão da Doença , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiopatologia , Adulto , Idoso , Ritmo alfa/fisiologia , Seguimentos , Humanos , Neuroestimuladores Implantáveis , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de SaúdeRESUMO
A deep brain stimulation system capable of closed-loop neuromodulation is a type of bidirectional deep brain-computer interface (dBCI), in which neural signals are recorded, decoded, and then used as the input commands for neuromodulation at the same site in the brain. The challenge in assuring successful implementation of bidirectional dBCIs in Parkinson's disease (PD) is to discover and decode stable, robust and reliable neural inputs that can be tracked during stimulation, and to optimize neurostimulation patterns and parameters (control policies) for motor behaviors at the brain interface, which are customized to the individual. In this perspective, we will outline the work done in our lab regarding the evolution of the discovery of neural and behavioral control variables relevant to PD, the development of a novel personalized dual-threshold control policy relevant to the individual's therapeutic window and the application of these to investigations of closed-loop STN DBS driven by neural or kinematic inputs, using the first generation of bidirectional dBCIs.
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Preeclampsia is characterized by development of hypertension during pregnancy and reduced placental perfusion. Previous studies in a rat model of placental ischemia-induced hypertension demonstrated that inhibiting complement activation attenuated increased maternal blood pressure with C3a and C5a identified as the important products of complement activation. Given that in other forms of ischemia both natural IgM and antigen antibody complexes initiate complement activation, we hypothesized that placental ischemia exposes neoepitopes recognized by IgM to cause local complement activation and hypertension. Alternatively, we postulated that autoantibody to angiotensin II Type 1 receptor (AT1-AA) interacts with AT1 receptors to cause complement activation. Since complement activation occurs in kidney and placenta in preeclampsia, we used immunohistochemistry to determine IgM deposition and local complement activation in each organ (C3 deposition), and quantitative real-time polymerase chain reaction (qRT-PCR) to quantitate mRNA for endogenous regulators of complement activation CD55, CD59 and Complement receptor 1-related gene/protein y (Crry). On gestation day (GD)14.5, timed pregnant Sprague Dawley rats underwent Sham surgery or placement of clips on inferior abdominal aorta and ovarian arteries to create placental ischemia using the reduced utero-placental perfusion pressure (RUPP) model. As previously reported, RUPP surgery increased mean arterial pressure and circulating C3a on GD19.5. In placenta, IgM and C3 deposition increased, whereas mRNA for complement regulators Crry and CD59 decreased along with Crry protein in RUPP compared to Sham treated animals. In kidney, IgM deposition increased in animals subjected to RUPP vs Sham surgery without a significant change in C3 deposition and coincident with an increase in mRNA for CD55 and CD59. The AT1 receptor antagonist losartan prevents placental ischemia-induced hypertension as well as AT1-AA interaction with AT1 receptors. However, losartan did not attenuate complement activation as measured by circulating C3a or placental C3 deposition. Importantly, our studies indicate that following placental ischemia, complement activation is not due to AT1-AA but is associated with IgM deposition. These studies suggest a role for natural antibodies interacting with placental ischemia-induced neoepitopes to activate complement and contribute to hypertension.