Prenatal Metyrapone Treatment Modulates Neonatal Cerebrovascular Structure, Function and Vulnerability to Mild Hypoxic-Ischemic Injury.

This study explored the hypothesis that late gestational reduction of corticosteroids transforms the cerebrovasculature, and modulates postnatal vulnerability to mild hypoxic-ischemic (HI) injury. Four groups of Sprague-Dawley neonates were studied: 1) Sham-Control; 2) Sham-MET; 3) HI-Control; 4) HI-MET. Metyrapone (MET), a corticosteroid synthesis inhibitor, was administered via drinking water from gestational day 11 to term. In Shams, MET administration: 1) decreased reactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis to surgical trauma in P9 pups by 37%; 2) promoted cerebrovascular contractile differentiation in middle cerebral arteries (MCA); 3) decreased compliance up to 46%, and increased depolarization-induced calcium mobilization n MCAs by 28%; 4) mildly increased hemispheric cerebral edema by 5%, decreased neuronal degeneration by 66% and increased astrogial and microglial activation by 10-fold and 4-fold, respectively; and 5) increased righting reflex times by 29%. Regarding HI, metyrapone-induced fetal transformation: 1) diminished reactivity of the HPA axis to HI-induced stress in P9/P10 pups; 2) enhanced HI-induced contractile de-differentiation in MCAs; 3) lessened the effects of HI on MCA compliance and calcium mobilization; 4) decreased HI-induced neuronal injury but unmasked regional HI-induced depression of microglial activation; and 5) attenuated the negative effects of HI on open field exploration, but enhanced the detrimental effects of HI on nega...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - Category: Physiology Authors: Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research

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Publication date: Available online 30 October 2019Source: Physiology &BehaviorAuthor(s): T.S. Souto, F.S.N. Nakao, C.A. Giriko, C.T. dias, A.I.P Cheberle, R.H. lambertucci, C. Mendes-da-SilvaAbstractHigh-fat diets (HFDs) during pregnancy may damage the neural development and emotional behavior of rat offspring. Therefore, we investigated the neurobehavioral development of rat offspring who were fed a control diet (CD) or an HFD with lard (HFD-lard) or canola oil (HFD-canola oil), during pregnancy. Offspring's neurodevelopment (somatic growth, physical maturation, and ontogenesis reflex) was assessed while they were suc...
Source: Physiology and Behavior - Category: Physiology Source Type: research
Psychological stress is recognized as a major modifiable risk factor for adult non-communicable disease (NCD) that includes depression, type 2 diabetes mellitus, and cardiovascular disease. Dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity resulting in either exaggerated or blunted cortisol responses, and altered autonomic cardiovascular control have been thought to underlie this association. The developmental origins hypothesis proposes that impaired nutrition during fetal and early postnatal growth is associated with a higher NCD risk later in life. Maternal nutrients are vital for fetal growth and deve...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Publication date: Available online 25 July 2019Source: Respiratory Physiology &NeurobiologyAuthor(s): Paulina M. Getsy, Catherine A. Mayer, Peter M. MacFarlane, Frank J. Jacono, Christopher G. WilsonAbstractAcute Lung Injury (ALI) alters pulmonary reflex responses, in part due to changes in modulation within the lung and airway neuronal control networks. We hypothesized that synaptic efficacy of nucleus tractus solitarii (nTS) neurons, receiving input from lung, airway, and other viscerosensory afferent fibers, would decrease following ALI. Sprague Dawley neonatal rats (postnatal days 9–11) were given intratrache...
Source: Respiratory Physiology and Neurobiology - Category: Respiratory Medicine Source Type: research
Conclusion and Perspectives The IL-6/JAK/STAT signaling cascade plays a dominant role in skeletal muscle pathophysiology. IL-6 autocrine, paracrine, and endocrine functions assign to its downstream effectors pivotal importance in skeletal muscle-wasting-associated diseases and other multiple system diseases where muscle acts in communication with other organs. Targeting the components of the JAK/STAT pathway recently emerged as a strategic approach for the treatment of inflammatory diseases and human cancer. This review highlights the opposite outcomes on muscle biology caused by the amount of local and systemic release ...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Conclusions: Magnesium sulfate is an important adjuvant drug in the practice of anesthesia, with several clinical effects and a low incidence of adverse events when used at recommended doses. Introduction Magnesium is the fourth most common ion in the body, and it participates in several cellular processes, including protein synthesis, neuromuscular function and stability of nucleic acid, as well as regulating other electrolytes such as calcium and sodium. Magnesium acts as a cofactor in protein synthesis, neuromuscular function and stability and the function of nucleic acids. It is a component of adenosine 5-triph...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In this study, a link between mitochondrial changes and infant temperament has also been suggested. Maternal psychosocial stress and lifetime trauma have been associated with decreased mitochondrial DNA copy number in the placenta (115, 116).IndividualityChronic stress links changes in the epigenetic landscape with health conditions (117). Different cell types are characterized by distinct patterns of gene expression due to developmental, environmental, physiological, and pathological reasons (117). Epigenetic mechanisms affect gene function in a dynamic way as a result of different environmental exposures during fetal dev...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Katherine Samaras1,2,3*, Henrik Tevaerai4, Michel Goldman5, Johannes le Coutre6,7 and Jeff M. P. Holly8 1Department of Endocrinology, St Vincent's Hospital, Darlinghurst, NSW, Australia 2Diabetes and Metabolism, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia 3St Vincent's Hospital, St Vincent's Clinical School, Darlinghurst, NSW, Australia 4Bern University Hospital, Bern, Switzerland 5Institute for Interdisciplinary Innovation in Healthcare, Universite Libre de Bruxelles, Bruxelles, Belgium 6Department of Medicine, Imperial College London, London, United Kingdom 7Nes...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Conclusion Currently available pharmacotherapies for PTSD are poorly effective on a substantial proportion of patients. Given this high rate of pharmacological unresponsiveness, further studies are needed to extend the knowledge of the basic mechanisms associated with the pathophysiology of this disorder. The findings discussed in this review suggest that DAergic dysfunction, especially genetic-dependent DAergic alteration, plays a prominent role in the pathophysiology of PTSD; as a consequence, drugs targeting the DAergic system might be therapeutically relevant. A better understanding of how and which DAergic dysfunctio...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroinfla...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion These data demonstrated that the VTA played a functional role in chronic visceral pain and depression, and the CRH-containing neurons in hypothalamic PVN may be implicated in the onset and maintenance of the chronic visceral pain and depression via the activation of dopamine in the VTA. PMID: 29623778 [PubMed - as supplied by publisher]
Source: Neurological Research - Category: Neurology Tags: Neurol Res Source Type: research
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