Proteomic study of left ventricle and cortex in rats after myocardial infarction.

Myocardial infarction (MI) induces neuroinflammation indirectly, chronic neuroinflammation may cause neurodegenerative diseases. Changes in the proteomics of heart and brain tissue after MI may shed new light on the mechanisms involved in neuroinflammation. This study explored brain and heart protein changes after MI with a data-independent acquisition (DIA) mode proteomics approach. Permanent ligation of the left anterior descending coronary artery (LAD) was performed in the heart of rats, and the immunofluorescence of microglia in the brain cortex was performed at 1d, 3d, 5d, and 7d after MI to detect the neuroinflammation. Then proteomics was accomplished to obtain the vital proteins in the heart and brain post-MI. The results show that the number of microglia was significantly increased in the Model-1d group, the Model-3d group, the Model-5d group, and the Model-7d group compared to the Sham group. Various proteins were obtained through DIA proteomics. Linking to key targets of brain disease, 14 proteins were obtained in the brain cortex. Among them, elongation of very long chain fatty acids protein 5 (ELOVL5) and ATP-binding cassette subfamily G member 4 (ABCG4) were verified through western blotting (WB). The results of WB were consistent with the proteomics results. Therefore, these proteins may be related to the pathogenesis of neuroinflammation after MI.

Heart-brain interaction in cardiogenic dementia: pathophysiology and therapeutic potential.

Diagnosis and treatment of patients with cardiovascular and neurologic diseases primarily focus on the heart and brain, respectively. An increasing number of preclinical and clinical studies have confirmed a causal relationship between heart and brain diseases. Cardiogenic dementia is a cognitive impairment caused by heart dysfunction and has received increasing research attention. The prevention and treatment of cardiogenic dementia are essential to improve the quality of life, particularly in the elderly and aging population. This study describes the changes in cognitive function associated with coronary artery disease, myocardial infarction, heart failure, atrial fibrillation and heart valve disease. An updated understanding of the two known pathogenic mechanisms of cardiogenic dementia is presented and discussed. One is a cascade of events caused by cerebral hypoperfusion due to long-term reduction of cardiac output after heart disease, and the other is cognitive impairment regardless of the changes in cerebral blood flow after cardiac injury. Furthermore, potential medications for the prevention and treatment of cardiogenic dementia are reviewed, with particular attention to multicomponent herbal medicines.

Effect of Naoxintong Capsule on Microglia and Proteomics of Cortex After Myocardial Infarction in Rats.

Neuroinflammation caused by microglia in the central nervous system (CNS) is observed after myocardial infarction (MI). However, the inflammatory response mechanism remains unclear. BuChang Naoxintong capsule (NXT) is a Chinese medicine for treating ischemic cardio-cerebrovascular diseases, requiring more studies to understand the pharmacodynamic mechanism. Permanent ligation of the left anterior descending coronary artery (LAD) was performed in rats. Additionally, histopathological staining in the left ventricular (LV) and immunofluorescence within the brain cortex after 1 d and 7 d of MI were performed to determine the NXT pharmacodynamic action and best administration dosage. Proteomics helped obtain the essential proteins related to neuroinflammation and MI in the heart and brain tissue after 7 d of MI. Based on TTC, HE, Masson, and immunofluorescence staining results of CD206 and IBA-1, NXT demonstrated a better pharmacodynamic action towards myocardial injury and neuroinflammation after 7 d of MI. Moreover, the human equivalent dosage of NXT (220 mg/kg) became the best administration dose. The proteome bioinformatics analysis in the LV and brain cortex was performed. Thus, the elongation of very long-chain fatty acids protein 5 (ELOVL5) and ATP-binding cassette subfamily G member 4 (ABCG4) became critical proteins related to MI and neuroinflammation. The western blotting results indicated that ABCG4 expression possessed the same trend as the proteomics results. The auto-dock results revealed that ABCG4 had a good binding ability with Ferulic acid, Paeoniflorin, and Tanshinone II A, the key ingredients of NXT. The cellular thermal shift assay results demonstrated that ABCG4 showed better thermal stability post-NXT treatment. NXT can improve myocardial injury, such as heart infarct size, pathological injury, myocardial fibrosis, and inflammatory cell infiltration. Additionally, brain neuroinflammation induced by microglia after MI affects the expression and structure of ABCG4. Thus, ABCG4 could be the key protein associated with MI and neuroinflammation.

Central control of cardiac activity as assessed by intra-cerebral recordings and stimulations.

Some of the most important integrative control centers for the autonomic nervous system are located in the brainstem and the hypothalamus. However, growing recent neuroimaging evidence support that a set of cortical regions, named the central autonomic network (CAN), is involved in autonomic control and seems to play a major role in continuous autonomic cardiac adjustments to high-level emotional, cognitive or sensorimotor cortical activities. Intracranial explorations during stereo-electroencephalography (SEEG) offer a unique opportunity to address the question of the brain regions involved in heart-brain interaction, by studying: (i) direct cardiac effects produced by the electrical stimulation of specific brain areas; (ii) epileptic seizures inducing cardiac modifications; (iii) cortical regions involved in cardiac interoception and source of cardiac evoked potentials. In this review, we detail the available data assessing cardiac central autonomic regulation using SEEG, address the strengths and also the limitations of this technique in this context, and discuss perspectives. The main cortical regions that emerge from SEEG studies as being involved in cardiac autonomic control are the insula and regions belonging to the limbic system: the amygdala, the hippocampus, and the anterior and mid-cingulate. Although many questions remain, SEEG studies have already demonstrated afferent and efferent interactions between the CAN and the heart. Future studies in SEEG should integrate these afferent and efferent dimensions as well as their interaction with other cortical networks to better understand the functional heart-brain interaction.

Oxygen Metabolism-induced Stress Response Underlies Heart-brain Interaction Governing Human Consciousness-breaking and Attention.

Neuroscientists have emphasized visceral influences on consciousness and attention, but the potential neurophysiological pathways remain under exploration. Here, we found two neurophysiological pathways of heart-brain interaction based on the relationship between oxygen-transport by red blood cells (RBCs) and consciousness/attention. To this end, we collected a dataset based on the routine physical examination, the breaking continuous flash suppression (b-CFS) paradigm, and an attention network test (ANT) in 140 immigrants under the hypoxic Tibetan environment. We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention. The results showed that RBC function, via two independent neurophysiological pathways, not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control. Importantly, consciousness played a fundamental role in executive function which might be associated with the level of perceived stress. These results indicated the important role of oxygen-transport in heart-brain interactions, in which the related stress response affected consciousness and executive control. The findings provide new insights into the neurophysiological schema of heart-brain interactions.

Oxygen Metabolism-induced Stress Response Underlies Heart-brain Interaction Governing Human Consciousness-breaking and Attention / 神经科学通报·英文版

Neuroscientists have emphasized visceral influences on consciousness and attention, but the potential neurophysiological pathways remain under exploration. Here, we found two neurophysiological pathways of heart-brain interaction based on the relationship between oxygen-transport by red blood cells (RBCs) and consciousness/attention. To this end, we collected a dataset based on the routine physical examination, the breaking continuous flash suppression (b-CFS) paradigm, and an attention network test (ANT) in 140 immigrants under the hypoxic Tibetan environment. We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention. The results showed that RBC function, via two independent neurophysiological pathways, not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control. Importantly, consciousness played a fundamental role in executive function which might be associated with the level of perceived stress. These results indicated the important role of oxygen-transport in heart-brain interactions, in which the related stress response affected consciousness and executive control. The findings provide new insights into the neurophysiological schema of heart-brain interactions.

Cardiac Stroke Volume Index Is Associated With Early Neurological Improvement in Acute Ischemic Stroke Patients.

Early neurological improvement as assessed with the NIH stroke scale (NIHSS) at 24 h has been associated with improved long-term functional outcomes following acute ischemic stroke (AIS). Cardiac dysfunction is often present in AIS, but its association with outcomes is incompletely defined. We performed a pilot study to evaluate the association between non-invasively measured cardiac parameters and 24-h neurological improvement in prospectively enrolled patients with suspected AIS who presented within 12 h of symptom-onset and had an initial systolic blood pressure>140 mm Hg. Patients receiving thrombolytic therapy or mechanical thrombectomy were excluded. Non-invasive pulse contour analysis was used to measure mean arterial blood pressure (MAP), cardiac stroke volume index (cSVI), cardiac output (CO) and cardiac index (CI). Transcranial Doppler recorded mean middle cerebral artery flow velocity (MFV). We defined a decrease of 4 NIHSS points or NIHSS ≤ 1 at 24-h as neurological improvement. Of 75 suspected, 38 had confirmed AIS and did not receive reperfusion therapy. Of these, 7/38 (18.4%) had neurological improvement over 24 h. MAP was greater in those without improvement (108, IQR 96-123 mm Hg) vs. those with (89, IQR 73-104 mm Hg). cSVI, CO, and MFV were similar between those without and with improvement: 37.4 (IQR 30.9-47.7) vs. 44.7 (IQR 42.3-55.3) ml/m2; 5.2 (IQR 4.2-6.6) vs. 5.3 (IQR 4.7-6.7) mL/min; and 39.9 (IQR 32.1-45.7) vs. 34.4 (IQR 27.1-49.2) cm/s, respectively. Multivariate analysis found MAP and cSVI as predictors for improvement (OR 0.93, 95%CI 0.85-0.98 and 1.14, 95%CI 1.03-1.31). In this pilot study, cSVI and MAP were associated with 24-h neurological improvement in AIS.

Biophysics-based statistical learning: Application to heart and brain interactions.

Initiatives such as the UK Biobank provide joint cardiac and brain imaging information for thousands of individuals, representing a unique opportunity to study the relationship between heart and brain. Most of research on large multimodal databases has been focusing on studying the associations among the available measurements by means of univariate and multivariate association models. However, these approaches do not provide insights about the underlying mechanisms and are often hampered by the lack of prior knowledge on the physiological relationships between measurements. For instance, important indices of the cardiovascular function, such as cardiac contractility, cannot be measured in-vivo. While these non-observable parameters can be estimated by means of biophysical models, their personalisation is generally an ill-posed problem, often lacking critical data and only applied to small datasets. Therefore, to jointly study brain and heart, we propose an approach in which the parameter personalisation of a lumped cardiovascular model is constrained by the statistical relationships observed between model parameters and brain-volumetric indices extracted from imaging, i.e. ventricles or white matter hyperintensities volumes, and clinical information such as age or body surface area. We explored the plausibility of the learnt relationships by inferring the model parameters conditioned on the absence of part of the target clinical features, applying this framework in a cohort of more than 3 000 subjects and in a pathological subgroup of 59 subjects diagnosed with atrial fibrillation. Our results demonstrate the impact of such external features in the cardiovascular model personalisation by learning more informative parameter-space constraints. Moreover, physiologically plausible mechanisms are captured through these personalised models as well as significant differences associated to specific clinical conditions.

Heart Rate Variability as an Index of Differential Brain Dynamics at Rest and After Acute Stress Induction.

The brain continuously receives input from the internal and external environment. Using this information, the brain exerts its influence on both itself and the body to facilitate an appropriate response. The dynamic interplay between the brain and the heart and how external conditions modulate this relationship deserves attention. In high-stress situations, synchrony between various brain regions such as the prefrontal cortex and the heart may alter. This flexibility is believed to facilitate transitions between functional states related to cognitive, emotional, and especially autonomic activity. This study examined the dynamic temporal functional association of heart rate variability (HRV) with the interaction between three main canonical brain networks in 38 healthy male subjects at rest and directly after a psychosocial stress task. A sliding window approach was used to estimate the functional connectivity (FC) among the salience network (SN), central executive network (CEN), and default mode network (DMN) in 60-s windows on time series of blood-oxygen-level dependent (BOLD) signal. FC between brain networks was calculated by Pearson correlation. A multilevel linear mixed model was conducted to examine the window-by-window association between the root mean square of successive differences between normal heartbeats (RMSSD) and FC of network-pairs across sessions. Our findings showed that the minute-by-minute correlation between the FC and RMSSD was significantly stronger between DMN and CEN than for SN and CEN in the baseline session [b = 4.36, t(5025) = 3.20, p = 0.006]. Additionally, this differential relationship between network pairs and RMSSD disappeared after the stress task; FC between DMN and CEN showed a weaker correlation with RMSSD in comparison to baseline [b = -3.35, t(5025) = -3.47, p = 0.006]. These results suggest a dynamic functional interplay between HRV and the functional association between brain networks that varies depending on the needs created by changing conditions.

A New Integrative Theory of Brain-Body-Ecosystem Medicine: From the Hippocratic Holistic View of Medicine to Our Modern Society.

Humans are increasingly aware that their fate will depend on the wisdom they apply in interacting with the ecosystem. Its health is defined as the condition in which the ecosystem can deliver and continuously renew its fundamental services. A healthy ecosystem allows optimal interactions between humans and the other biotic/abiotic components, and only in a healthy ecosystem can humans survive and efficiently reproduce. Thus, both the human and ecosystem health should be considered together in view of their interdependence. The present article suggests that this relationship could be considered starting from the Hippocrates (460 BC-370 BC) work "On Airs, Waters, and Places" to derive useful medical and philosophical implications for medicine which is indeed a topic that involves scientific as well as philosophical concepts that implicate a background broader than the human body. The brain-body-ecosystem medicine is proposed as a new more complete approach to safeguarding human health. Epidemiological data demonstrate that exploitation of the environment resulting in ecosystem damage affects human health and in several instances these diseases can be detected by modifications in the heart-brain interactions that can be diagnosed through the analysis of changes in heart rate variability.

The Heart as a Psychoneuroendocrine and Immunoregulatory Organ.

The heart can be viewed not just as muscle pump but also as an important checkpoint for a complex network of nervous, endocrine, and immune signals. The heart is able to process neurological signals independently from the brain and to crosstalk with the endocrine and immune systems. The heart communicates with the psyche through the neuro-endocrine-immune system in a highly integrated way, in order to maintain the homeostasis of the whole body with peculiarities specific to males and females.

Radiographic and Clinical Predictors of Cardiac Dysfunction Following Isolated Traumatic Brain Injury.

INTRODUCTION: Although cardiac dysfunction after traumatic brain injury (TBI) has been described, there is little data regarding the association of radiographic severity and particular lesions of TBI with the development of cardiac dysfunction. We hypothesize that the Rotterdam or Marshall scores and particular TBI lesions are associated with the development of cardiac dysfunction after isolated TBI. METHODS: We performed a retrospective cohort study. Adult patients with isolated TBI who underwent echocardiography between 2003 and 2010 were included. A board-certified neuroradiologist assessed the first computed tomography head, assigning the Rotterdam and Marshall scores and the type of TBI. Cardiac dysfunction was defined as either systolic or all cause based on the first echocardiogram after TBI. Demographic, radiological, and clinical variables were used in our analysis. RESULTS: A total of 139 patients were identified, with 20 having isolated systolic dysfunction. The Marshall and Rotterdam scores were not associated with the development of cardiac dysfunction. Only head Abbreviated Injury Scale was found to be an independent predictor of systolic cardiac dysfunction (relative risk: 2.70, 95% confidence interval: 1.19-6.13; P = .02). CONCLUSIONS: No specific radiographic variable was found to be an independent predictor of cardiac dysfunction. Further study into clinical or radiological features that would warrant an echocardiogram is warranted, as it may direct patient management.

Efficacy of an Emotion Self-regulation Program for Promoting Development in Preschool Children.

This work reports the results of an evaluation study to assess the efficacy of the Early HeartSmarts (EHS) program in schools of the Salt Lake City, Utah, School District. The EHS program is designed to guide teachers with methods that support young children (3-6 y old) in learning emotion self-regulation and key age-appropriate socioemotional competencies with the goal of facilitating their emotional, social, and cognitive development. The study was conducted over one school year using a quasiexperimental longitudinal field research design with 3 measurement points (baseline, preintervention, and postintervention) using The Creative Curriculum Assessment (TCCA), a teacher-scored, 50-item instrument measuring students growth in 4 areas of development: social/emotional, physical, cognitive, and language development. Children in 19 preschool classrooms in the Salt Lake City School District were divided into intervention and control group samples (n = 66 and n = 309, respectively; mean age = 3.6 y). The intervention classes were specifically selected to target children of lower socioeconomic and ethnic minority backgrounds. Overall, there is compelling evidence of the efficacy of the EHS program in increasing total psychosocial development and each of the 4 development areas measured by the TCCA: the results of a series of analyses of covariance found a strong, consistent pattern of large, significant differences on the development measures favoring preschool children who received the EHS program over those in the control group.

Este trabajo informa los resultados de un estudio de evaluación de la eficacia del programa Early Heartsmarts (EHS) en las escuelas del Distrito Escolar de Salt Lake City, Utah. El programa EHS está diseñado para orientar a los maestros respecto de métodos de asistencia a niños pequeños (entre 3 y 6 años de edad) en el aprendizaje de técnicas de autorregulación emocional y competencias socioemocionales fundamentales, adecuadas para su edad, con el fin de favorecer su desarrollo emocional, social y cognitivo. Este estudio se realizó durante un año escolar, conforme un diseño de investigación de campo cuasi experimental y longitudinal, diseñada con tres puntos de medición (punto de partida, intervención previa e intervención posterior), en la que se utilizó una Evaluación del Currículo Creativo (TCCA, por sus siglas en inglés), un instrumento calificado por el maestro de 50 puntos para medir el crecimiento de los estudiantes en 4 áreas del desarrollo: social y emocional, físico, cognitivo y desarrollo del lenguaje. Los niños de los 19 salones de clase de nivel preescolar en el Distrito Escolar de Salt Lake City, se analizaron de manera fraccionada según muestras de intervención y de control de grupo (n=66 y n=309, respectivamente; edad promedio=3 a 6 años). Las clases de intervención fueron seleccionadas específicamente para examinar a niños de bajo nivel socioeconómico y pertenecientes a minorías étnicas. En general, existen pruebas convincentes de la eficacia del programa EHS para fomentar el desarrollo psicosocial total. Respecto de cada una de las 4 áreas de desarrollo que fueron medidas por la TCCA: los resultados de una serie de análisis de la covarianza mostraron un patrón sólido y consistente de diferencias notorias y significativas en las medidas de desarrollo que favorecen a los niños de preescolar que recibieron el programa EHS, respecto de aquellos del grupo de control.