Editorial: Neurocardiovascular Diseases: New Aspects of the Old Issues

Abstract

Editorial on the Research Topic Neurocardiovascular Diseases: New Aspects of the Old Issues Concept of neuro-cardiovascular diseases (NCVD) is one fruitful approach that enables the comprehension of the pathological processes raising along the brain-heart & blood vessel axes from the integrative prospective. That is the reason why multidisciplinary and interdisciplinary approaches result in novel insights into pathophysiological processes bringing new directions for therapeutic development, both at the laboratory bench and at the clinical bedside. NCVD comprises the group of pathologies that have as a primary pathological substrate the changes in neurochemical, neurophysiological and neuroanatomical levels of the autonomic nervous system (ANS) and its regulated organs (e.g., heart, blood vessels). A striking fact is that “cardiovascular disease is the leading cause of death in the world today and will remain so by the year 2020” (The WHO MONICA Project, Investigators, 1988) strongly supports the need for new insights into cardiovascular regulatory mechanisms (Bojić, 2003). A picture of the classical cardiovascular risk factors from the prospective of neural cardiovascular control, links these factors with stress. The central topic of NCV physiology is related to stress-induced disfunction (e.g., hypertension, Du et al., 2017), emotional stress coping-cigarette smoking, obesity, Strickland et al., 2007) and stress-releasing strategies (exercise, Acevedo et al., 2006; Webb et al., 2017). Central questions of neurophysiology of stress is: a. Identification of different brain networks activated during stress b. Spacial and temporal patterns of their activation c. Identification of neuronal hubs coupling cognitive-emotional neural networks with body effectors, like the hypothalamus-pituitary-adrenal (HPA) and the sympathetic-adrenomedullary axis (SAM) (Ulrich-Lai and Herman, 2009; Godoy et al., 2018). The interaction of the heart and vessels with the central and peripheral nervous systems represents the major topic of the basic neuro-cardiovascular research, with the current aim of the field being to highlight the mechanisms of devastating effects of stress upon the cardiovascular system. In the review of Dampney the focus was on anatomical basis and functional role of the dorsolateral periaqueductal gray (dlPAG) in generating behavioral and autonomic responses to real and perceived emotional stressors. Central position and integratory function of this structure, between higher cortical regions (auditory, secondary visual, olphactory; medial prefrontal cortex -MPC, hypothalamus and lower brainstem structures), qualifies it as a crucial, emotional stress mediator neural hub. Though the review reports, parallel and comparative results obtained in different species, the guiding theme is the enlightening of the understanding of the morpho-functional substrate affiliated with emotional stress response in humans. Crucial for understanding of the behavioral response to the perceived emotional stress are the inputs from the MPC to the dlPAG. The species-specific MPC subregion of the primate brain, the area 10 m, has the largest volume in humans with respect to other primate species. Allman and collaborates (Allman et al., 2002) describe this structure as a comparator of current and memorized behavioral states, and as a consequent decision-maker about future, potentially advantageous behavior. Its high activation and direct interface with dlPAG points to its special role in complex emotional responses, resulting from such comparisons. In conclusion, dlPAG is presented as integrator of the reactions of both the conscious and the unconscious to threatening stimuli with dependent autonomic networks (i.e., cardiorespiratory network) which support the behavioral response to stress and threatening stimuli. Future studies need to address the questions of chemical phenotyping of the dlPAG and other extensive stress mediating brain networks; the question of morpho-functional plasticity with respect to timing and duration of stress exposure; association of stress-induced morpho-functional changes of critical brain networks associated with different cardiovascular pathologies, as well as the question of genetic predisposition to developing of specific pathological entities like NCVD on the order of short or long time scales. The impact of peripheral information on neural mediation of the cardiovascular (CVS) response can be crucial to the development of pathologies initiated by physical stressors like injury. When a physical stressor is recognized by the brainstem through pain, inflammation and other signals, both fast SAM and sluggish HPA responses are activated (Godoy et al., 2018). Up to the present it is not known what the role of pre-stimulus of the ANS regime is for development of the compartment syndrome. In this line, the study that investigated the effect of peripheral neural input to the heart rate regulating network by Watanabe and Hotta for the first time examined the specific cardiac autonomic changes induced by the bio-mechanical pressure stimulation of skeletal muscle. The authors identified sympathetic nervous system as the effector of changes in heart rate and blood pressure. In addition, it was demonstrated that the tonic level of pre-stimulus sympathetic neural activity determines the direction of induced heart rate changes and changes to blood pressure. This data could be of particular importance for understanding the compartment syndrome, the condition of muscle ischemic necrosis due to excessive intramuscular pressure and blood hypoperfusion. Future studies are necessary for revealing the site of the interaction of peripheral muscle pressure, stretching and contraction stimulus of the CVS neural networks (spinal or brainstem), and chemical phenotyping for the purpose of pharmacological intervention, and the role of tonic pre-stimulus...