Pharmacological Stimuli Research Articles

Endothelial Dysfunction in Childhood Cancer Survivors: A Narrative Review.

Assessment of endothelial dysfunction in cancer survivors may have a role in the early identification of non-communicable diseases and cardiovascular late effects. Oncological therapies may impair endothelial function. Therefore, in patients such as childhood cancer survivors who could benefit from early cardioprotective pharmacological interventions, it is essential to monitor endothelial function, even if the optimal methodology for investigating the multifaceted aspects of endothelial dysfunction is still under debate. Biochemical markers, as well as invasive and non-invasive tools with and without pharmacological stimuli have been studied. Human clinical studies that have examined lifestyle or cancer treatment protocols have yielded evidence showing the involvement of lipid and lipoprotein levels, glycemic control, blood pressure, adiposity, inflammation, and oxidative stress markers on the state of endothelial health and its role as an early indicator of cardiometabolic risk. However, with regards to pharmacological interventions, cautious interpretation of the result attained whilst monitoring the endothelial function is warranted due to methodological limitations and substantial heterogeneity of the results reported in the published studies. In this narrative review, an overview of evidence from human clinical trials examining the effects of cancer therapies on endothelial disease is provided together with a discussion of endothelial function assessment using the different non-invasive techniques available for researchers and clinicians, in recent years.

Комбинированная терапия «метформин + глимепирид» у больных сахарным диабетом 2-го типа (молекулярные механизмы оптимизации реабилитирующего действия)

Обзор посвящен описанию молекулярных механизмов терапевтического действия комбинации пероральных антидиабетических препаратов «метформин + глимепирид», направленного на коррекцию обоих дефектов, которые определяют развитие метаболических нарушений при сахарном диабете 2-го типа, а именно относительного дефицита инсулина и инсулинорезистентности. Сочетание метформина с глимепиридом оптимально в плане терапевтического воздействия на обе молекулы, недостаточная активность которых определяет метаболическое состояние инсулинорезистентности, соответственно аденозинмонофосфатактивируемую протеинкиназу и пролифератором пероксисом активированный рецептор γ. Кроме того, метформину присуща уникальная способность устранять феномен «гипергликемической памяти» за счет повышения экспрессии и активности сиртуина-1. С другой стороны, препарат сульфонилмочевины третьей генерации глимепирид обеспечивает «щадящую» стимуляцию β-клеток, что сохраняет физиологическое соотношение проинсулин/инсулин и замедляет развитие феномена десенситизации β-клеток к физиологическим и фармакологическим стимулам. Глимепирид сохраняет защитный феномен ишемического прекондиционирования и расширяет спектр терапевтического влияния на патофизиологические составляющие инсулинорезистентности за счет инсулинмиметического и инсулинсенситайзерного эффекта, а также потенцирует благоприятные эффекты метформина (в частности, через адипонектин). С этим связано достижение оптимизированной терапевтической эффективности фармкомбинации при снижении побочного действия (уменьшение дозы глимепирида, метформина).

Environmental Enrichment Induces Meningeal Niche Remodeling through TrkB-Mediated Signaling.

Neural precursors (NPs) present in the hippocampus can be modulated by several neurogenic stimuli, including environmental enrichment (EE) acting through BDNF-TrkB signaling. We have recently identified NPs in meninges; however, the meningeal niche response to pro-neurogenic stimuli has never been investigated. To this aim, we analyzed the effects of EE exposure on NP distribution in mouse brain meninges. Following neurogenic stimuli, although we did not detect modification of the meningeal cell number and proliferation, we observed an increased number of neural precursors in the meninges. A lineage tracing experiment suggested that EE-induced β3-Tubulin+ immature neuronal cells present in the meninges originated, at least in part, from GLAST+ radial glia cells. To investigate the molecular mechanism responsible for meningeal reaction to EE exposure, we studied the BDNF-TrkB interaction. Treatment with ANA-12, a TrkB non-competitive inhibitor, abolished the EE-induced meningeal niche changes. Overall, these data showed, for the first time, that EE exposure induced meningeal niche remodeling through TrkB-mediated signaling. Fluoxetine treatment further confirmed the meningeal niche response, suggesting it may also respond to other pharmacological neurogenic stimuli. A better understanding of the neurogenic stimuli modulation for meninges may be useful to improve the effectiveness of neurodegenerative and neuropsychiatric treatments.

Automatic Identification of Dendritic Branches and their Orientation

The structure of neuronal dendritic trees plays a key role in the integration of synaptic inputs in neurons. Therefore, characterization of the morphology of dendrites is essential for a better understanding of neuronal function. However, the complexity of dendritic trees, both when isolated and especially when located within neuronal networks, has not been completely understood. We developed a new computational tool, SOA (Segmentation and Orientation Analysis), which allows automatic measurement of the orientation of dendritic branches from fluorescence images of 2D neuronal cultures. SOA, written in Python, uses segmentation to distinguish dendritic branches from the image background and accumulates a database on the spatial direction of each branch. The database is then used to calculate morphological parameters such as the directional distribution of dendritic branches in a network and the prevalence of parallel dendritic branch growth. The data obtained can be used to detect structural changes in dendrites in response to neuronal activity and to biological and pharmacological stimuli.

Exercising in Hypoxia and Other Stimuli: Heart Rate Variability and Ventilatory Oscillations.

Periodic breathing is a respiratory phenomenon frequently observed in patients with heart failure and in normal subjects sleeping at high altitude. However, until recently, periodic breathing has not been studied in wakefulness and during exercise. This review relates the latest findings describing this ventilatory disorder when a healthy subject is submitted to simultaneous physiological (exercise) and environmental (hypoxia, hyperoxia, hypercapnia) or pharmacological (acetazolamide) stimuli. Preliminary studies have unveiled fundamental physiological mechanisms related to the genesis of periodic breathing characterized by a shorter period than those observed in patients (11~12 vs. 30~60 s). A mathematical model of the respiratory system functioning under the aforementioned stressors corroborated these data and pointed out other parameters, such as dead space, later confirmed in further research protocols. Finally, a cardiorespiratory interdependence between ventilatory oscillations and heart rate variability in the low frequency band may partly explain the origin of the augmented sympathetic activation at exercise in hypoxia. These nonlinear instabilities highlight the intrinsic “homeodynamic” system that allows any living organism to adapt, to a certain extent, to permanent environmental and internal perturbations.

HRV analysis: undependability of approximate entropy at locating optimum complexity in malnourished children.

Approximate Entropy is an extensively enforced metric to evaluate chaotic responses and irregularities of RR intervals sourced from an eletrocardiogram. However, to estimate their responses, it has one major problem - the accurate determination of tolerances and embedding dimensions. So, we aimed to overt this potential hazard by calculating numerous alternatives to detect their optimality in malnourished children. We evaluated 70 subjects split equally: malnourished children and controls. To estimate autonomic modulation, the heart rate was measured lacking any physical, sensory or pharmacologic stimuli. In the time series attained, Approximate Entropy was computed for tolerance (0.1→0.5 in intervals of 0.1) and embedding dimension (1→5 in intervals of 1) and the statistical significances between the groups by their Cohen's ds and Hedges's gs were totalled. The uppermost value of statistical significance accomplished for the effect sizes for any of the combinations was -0.2897 (Cohen's ds) and -0.2865 (Hedges's gs). This was achieved with embedding dimension = 5 and tolerance = 0.3. Approximate Entropy was able to identify a reduction in chaotic response via malnourished children. The best values of embedding dimension and tolerance of the Approximate Entropy to identify malnourished children were, respectively, embedding dimension = 5 and embedding tolerance = 0.3. Nevertheless, Approximate Entropy is still an unreliable mathematical marker to regulate this.

Effects of Ketoprofen and Morphine on Pain-Related Depression of Nestlet Shredding in Male and Female Mice.

A primary goal in pain treatment is restoration of behaviors that are disrupted by pain. Measures of pain interference indicate the degree to which pain interferes with activities in pain patients, and these measures are used to evaluate the effects of analgesic drugs. As a result of the emphasis on the expression and treatment of functional impairment in clinical settings, preclinical pain researchers have attempted to develop procedures for evaluation of pain-related functional impairment in laboratory animals. The goal of the present study was to develop and validate a low cost procedure for the objective evaluation of pain-related depression of home cage behavior in mice. On test days, a 5 × 5 cm Nestlet was weighed prior to being suspended from the wire lid of the home cage of individually housed male and female ICR mice. Over the course of experimental sessions, mice removed pieces of the suspended Nestlet, and began to build a nest with the material they removed. Thus, the weight of the pieces of Nestlet that remained suspended at various time points in the session provided an indicator of the rate of this behavior. The results indicate that Nestlet shredding was stable with repeated testing, and shredding was depressed by intra-peritoneal injection of 0.32% lactic acid. The non-steroidal anti-inflammatory drug ketoprofen blocked 0.32% lactic acid-induced depression of shredding, but did not block depression of shredding by a pharmacological stimulus, the kappa opioid receptor agonist U69,593. The μ-opioid receptor agonist morphine did not block 0.32% lactic acid-induced depression of shredding when tested up to doses that depressed shredding in the absence of lactic acid. When noxious stimulus intensity was reduced by decreasing the lactic acid concentration to 0.18%, morphine was effective at blocking pain-related depression of behavior. In summary, the data from the present study support consideration of the Nestlet shredding procedure for use in studies examining mechanisms, expression, and treatment of pain-related functional impairment.

Engineered cardiac tissue microsphere production through direct differentiation of hydrogel-encapsulated human pluripotent stem cells

Engineered cardiac tissues that can be directly produced from human induced pluripotent stem cells (hiPSCs) in scalable, suspension culture systems are needed to meet the demands of cardiac regenerative medicine. Here, we demonstrate successful production of functional cardiac tissue microspheres through direct differentiation of hydrogel encapsulated hiPSCs. To form the microspheres, hiPSCs were suspended within the photocrosslinkable biomaterial, PEG-fibrinogen (25 million cells/mL), and encapsulated at a rate of 420,000 cells/minute using a custom microfluidic system. Even at this high cell density and rapid production rate, high intra-batch and batch-to-batch reproducibility was achieved. Following microsphere formation, hiPSCs maintained high cell viability and continued to grow within and beyond the original PEG-fibrinogen matrix. These initially soft microspheres (<250 Pa) supported efficient cardiac differentiation; spontaneous contractions initiated by differentiation day 8, and the microspheres contained >75% cardiomyocytes (CMs). CMs responded appropriately to pharmacological stimuli and exhibited 1:1 capture up to 6.0 Hz when electrically paced. Over time, cells formed cell-cell junctions and aligned myofibril fibers; engineered cardiac microspheres were maintained in culture over 3 years. The capability to rapidly generate uniform cardiac microsphere tissues is critical for advancing downstream applications including biomanufacturing, multi-well plate drug screening, and injection-based regenerative therapies.

HRV Analysis: Unpredictability of Approximate Entropy in Chronic Obstructive Pulmonary Disease

Introduction: Approximate entropy (ApEn) is a widely imposed metric to evaluate a chaotic response and irregularities of RR-intervals from an electrocardiogram. Yet, the technique is problematic due to the accurate choice of the tolerance (r) and embedding dimension (M). We prescribed the metric to evaluate these responses in subjects exhibiting symptoms of chronic obstructive pulmonary disease (COPD) and we strived to overcome this disadvantage by applying different groupings to detect the optimal. Methods: We examined 38 subjects split equally: COPD and control. To evaluate autonomic modulation the heart rate was measured beat-by-beat for 30 min in a supine position without any physical, sensory, or pharmacological stimuli. In the time-series obtained the ApEn was then applied with set values for tolerance, r and embedding dimension, M. Then, the differences between the two groups and their effect size by two measures (Cohen’s ds and Hedges’s gs) were computed. Results: The highest value of statistical significance accomplished for any effect size statistical combinations undertaken was -1.13 for Cohen’s ds, and -1.10 for Hedges’s gs with embedding dimension, M = 2 and tolerance, r = 0.1. Conclusion: ApEn was capable of optimally identifying the decrease in chaotic response in COPD. The optimal combination of r and M for this were 0.1 and 2, respectively. Despite this, ApEn is a relatively unpredictable mathematical marker and the use of other techniques to evaluate a healthy or pathological condition is encouraged.

Chronic running and a corticosterone treatment attenuate astrocyte-like neural stem cell proliferation in the area postrema of the adult mouse brain

The discovery of neural stem cells (NSCs) in the adult mammalian brain has provided insights into an extra level of brain plasticity. The proliferation and differentiation of NSCs is modulated by various physiological, pathological, and pharmacological stimuli. NSCs were recently detected in the medulla oblongata of adult rodents and humans; however, their functional significance currently remains unknown. In the present study, we examined the effects of chronic wheel-running and a corticosterone (CORT) treatment on the proliferation of astrocyte-like NSCs in the area postrema (AP) and dentate gyrus (DG). Chronic running significantly decreased the number of bromodeoxyuridine (BrdU)-labeled astrocyte-like NSCs in the AP of adult mice, but markedly increased that of BrdU+ NSCs/neural progenitor cells in the DG. The chronic CORT treatment markedly reduced the number of BrdU+ astrocyte-like NSCs in the AP, but not in the DG. These results demonstrate that the proliferation of astrocyte-like NSCs in the medulla oblongata is decreased by chronic running and a CORT treatment.

Lack of drug- and cue-stimulated emissions of ultrasonic vocalizations in C57BL/6J mice repeatedly treated with amphetamine

The emission of ultrasonic vocalizations (USVs) is thought to communicate the behavioral and emotional states elicited in rodents by social and non-social stimuli. On this basis, studies of psychopharmacology in rats are increasingly utilizing USVs as a behavioral marker to evaluate the effects of drugs on the emotional state. Conversely, very limited information is available as to whether psychoactive drugs influence USV emissions in mice. To provide new insights in this respect, we evaluated the emission of USVs in C57BL/6J mice subjected to repeated treatment with the dopaminergic psychostimulant of abuse amphetamine. Mice were first allowed to perform social contacts in dyads, and 2 days later they received amphetamine (1−4 mg/kg, i.p.) in a test cage (× 5 administrations) on alternate days. Seven days after treatment discontinuation, mice were re-exposed to the test cage to evaluate whether the presentation of drug-paired environmental cues elicited calling behavior, and thereafter received an amphetamine challenge. An additional group of animals received the dopamine receptor agonist apomorphine (1−4 mg/kg, i.p.), to further clarify the role of dopamine transmission in calling behavior of mice. C57BL/6J mice emitted USVs during social contacts, but did not significantly vocalize after amphetamine administration, in response to amphetamine-paired environmental cues, and after apomorphine administration. These results indicate that C57BL/6J mice may respond differently to social and pharmacological stimuli in terms of USV emissions, and may lay the foundation for future studies aimed at clarifying whether USVs may be a useful behavioral marker in studies of psychopharmacology in mice.

Adenosine Monophosphate-Activated Protein Kinase, Oxidative Stress, and Diabetic Endothelial Dysfunction

Abstract Endothelial dysfunction characterized by impaired endothelium-dependent vaso-relaxation is one of the earliest detectable pathological events in smoking, diabetes, and many cardiovascular diseases including hypertension, atherosclerosis. Overwhelming data from human and animals demonstrate that the endothelial dysfunction associated with diabetes is due to the local formation of oxidants and free radicals. However, the mechanisms by which diabetes instigates oxidative stress, and those by which oxidative stress perpetuates endothelial dysfunction are the subjects of intensive research in the last 3 decades. The studies from us and others have demonstrated that adenosine monophosphate-activated protein kinase (AMPK), a well-characterized energy sensor and modulator, serves as a highly efficient sensor as AMPK can be activated by very low levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) generated by physiological, pharmacological, and pathologic stimuli (redox sensor). Interestingly, oxidants-activated AMPK feedback lowers the levels of ROS by either suppressing ROS/RNS from reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and mitochondria or by increasing the levels of antioxidant enzymes (redox modulator). Further, our studies demonstrate that AMPK's functions as a redox sensor and modulator are vital to maintain endothelial cell function under physiological conditions. Finally, we discover that under chronic oxidative stress or large influx of ROS, AMPK is particularly susceptible to inhibition by ROS. We conclude that oxidative inactivation of AMPK in diabetes perpetuates oxidative stress and accelerates atherosclerosis in diabetes.

High Anxiety Levels and Growth Hormone Secretion in Children with Short Stature

Growth hormone (GH) provocation test, which includes repeated blood measurements following pharmacological stimuli, may be stressful for the children and their family. Thirty-three short stature children with impaired growth rate were studied during GH provocation tests to determine if the test is associated with increased anxiety and if increased anxiety affects the test results.

Imaging Meets Cytometry: Analyzing Heterogeneous Functional Microscopic Data from Living Cell Populations

Biological tissue consists of populations of cells exhibiting different responses to pharmacological stimuli. To probe the heterogeneity of cell function, we propose a multiplexed approach based on real‐time imaging of the secondary messenger levels within each cell of the tissue, followed by extraction of the changes of single‐cell fluorescence over time. By utilizing a piecewise baseline correction, we were able to quantify the effects of multiple pharmacological stimuli added and removed sequentially to pancreatic islets of Langerhans, thereby performing a deep functional profiling for each cell within the islet. Cluster analysis based on the functional profile demonstrated dose‐dependent changes in statistical inter‐relationships between islet cell populations. We therefore believe that the functional cytometric approach can be used for routine quantitative profiling of the tissue for drug screening or pathological testing.

The venous contribution to cardiovascular performance: From systemic veins to left ventricular function: A review

The venous system contains ≈ 70 % of the total blood volume and is responsible in heart failure for key symptoms of congestion. It is active: it can increase or relax its tone with physiologic or pharmacologic stimuli. It is heterogeneous, behaves as a two-compartment model, compliant (splanchnic veins) and noncompliant (nonsplanchnic veins). It is dynamic in health and disease: in heart failure the vascular capacitance (storage space) is decreased and can result in volume redistribution from the abdominal compartment to the thoracic compartment (heart and lungs), which increases pulmonary pressures and precipitates pulmonary congestion. A noninvasive assessment of venous function, at rest and dynamically during stress, is warranted. The systemic haemodynamic congestion is assessed with inferior vena cava diameter and collapsibility. The pulmonary congestion is assessed with B-lines and pleural effusion. The contribution of left ventricular filling is assessed with end-diastolic volume, integrated with left ventricular function.

Dietary supplementation with whey protein improves systemic microvascular function in heart failure patients: a pilot study

Endothelial dysfunction is a well-known component of the pathophysiology of heart failure (HF), with proven prognostic value. Dietary supplementation with whey protein (WP) has been widely used to increase skeletal muscle mass, but it also has vascular effects, which are less understood. This study aimed to evaluate the effects of WP supplementation on the systemic microvascular function of HF patients. This was a blinded, randomized, placebo-controlled clinical trial that evaluated the effects of 12-week WP dietary supplementation on systemic microvascular function, in patients with HF New York Heart Association (NYHA) classes I/II. Cutaneous microvascular flow and reactivity were assessed using laser speckle contrast imaging, coupled with pharmacological local vasodilator stimuli. Fifteen patients (aged 64.5±6.2 years, 11 males) received WP supplementation and ten patients (aged 68.2±8.8 years, 8 males) received placebo (maltodextrin). The increase in endothelial-dependent microvascular vasodilation, induced by skin iontophoresis of acetylcholine, was improved after WP (P=0.03) but not placebo (P=0.37) supplementation. Moreover, endothelial-independent microvascular vasodilation induced by skin iontophoresis of sodium nitroprusside, was also enhanced after WP (P=0.04) but not placebo (P=0.42) supplementation. The results suggested that dietary supplementation with WP improved systemic microvascular function in patients with HF.

A Method to Induce Brown/Beige Adipocyte Differentiation from Murine Preadipocytes.

Adipocytes exhibit different morphological and functional characteristics, depending on their anatomical location, developmental origin, and stimulus. While white adipocytes tend to accumulate energy as triglycerides, brown and beige adipocytes tend to direct carbon sources to fuel thermogenesis. White and beige adipocytes originate from common progenitor cells, which are distinct from brown adipocyte precursors. Having a method to study white vs. beige vs. brown adipocyte differentiation may help to unveil the mechanisms driving distinct adipogenic programs. Preadipocytes can be cultured and differentiated in vitro using a combination of compounds to stimulate adipogenesis. Here, we describe and compare protocols designed to stimulate adipocyte differentiation and induce brown/beige-like or white-like characteristics in differentiating adipocytes. The protocols consist in exposing murine preadipocytes to pharmacological stimuli aimed at triggering adipogenesis and inducing (or not) a thermogenic gene expression program. After 8 days of differentiation with a pro-browning cocktail, immortalized preadipocytes isolated from interscapular brown fat (9B cells) or inguinal white fat (9W cells) from the same mouse expressed higher levels of brown/beige adipocyte markers (e.g., Ucp1) and pan-adipocyte differentiation markers (e.g., Pparg, Cebpa and aP2) when compared to the same cells differentiated with a cocktail that lacked brown/beige adipogenic inducers (i.e., rosiglitazone, T3, and indomethacin). Consistent with a higher thermogenic potential of brown vs. beige adipocytes, differentiated 9B cells expressed higher Ucp1 levels than differentiated 9W cells. This simple protocol may help researchers to understand mechanisms of adipogenesis and how adipocytes become thermogenic.

Neutrophil Extracellular Traps: New Aspects.

—Neutrophils are the “first line” of defense against pathogens in the locus of inflammation, where they use effector functions such as phagocytosis, degranulation, and formation of reactive oxygen species (ROS). In 2004, Artuto Zychlinsky characterized one more neutrophil effector function—the release of neutrophil extracellular traps (or NETs). NETs are a modified chromatin “decorated” by bactericidal proteins of granules, nucleus, and cytoplasm. The release of NETs can be activated by diverse physiological and pharmacological stimuli and depends on ROS, for which NADPH oxidase is the main source. In the process of NET formation, the release of bactericidal components of granules into the cytoplasm, modification of histones leading to chromatin decondensation, destruction of the nuclear envelope and cytoplasmic membrane with the involvement of gasdermin D protein, and, finally, the release of chromatin outside the cell occurs. At the same time, uncontrolled formation of NETs is a provoking factor in the development of many inflammatory and autoimmune diseases. NETs were found at autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, psoriasis, and vasculitis; NETs are involved in the pathogenesis of cardiovascular, pulmonary, and oncological diseases. In this review, the main ideas about the mechanisms of NET formation, as well as their role in physiological processes and pathogenesis of a number of diseases (including COVID-19), are discussed.

The Effect of Single or Multiple Doses of Grapefruit Juice on the Analgesic Effect of Ibuprofen in Mice

Grapefruit juice (GFJ) is a rich source of nutritional compounds but has been shown to alter the concentrations of several clinically useful drugs. Ibuprofen is a commonly used over-the counter-drug.&#x0D; Aim: This study aims to examine the effect of a single or multiple dose of GFJ on the analgesic effect of ibuprofen.&#x0D; Methodology: CD1 male mice were randomly distributed into four equal groups (n=9, each). The first group served as a control, the second group was given ibuprofen (100 mg/Kg) by oral gavage, the third group was given a single dose of GFJ (10 mg/Kg) by oral gavage followed by ibuprofen, and the fourth group was given a single dose of GFJ for five days and on the fifth day was given ibuprofen. The analgesic effect was tested using two methods with different mechanisms: thermal (hot plate) and chemical (acetic acid-induced abdominal constriction) pharmacologic stimuli models.&#x0D; Results: Both GFJ dosing regimen significantly increased the duration of abdominal constriction test when compared with ibuprofen group and did not exert any significant effect on the hot plate effect. This suggest that GFJ may affect the peripherally modulated analgesic effect of ibuprofen. Conclusion: The observed effect of GFJ on ibuprofen analgesic effect warrants further studies on their impact and clinical significance on humans.

Cerebral dysautonomy as a clinical repercussion in children with traumatic brain injury

Introduction: Dysautonomia or Paroxysmal Sympathetic Hyperactivity (PSH) affects more than 50% of patients suffering from severe traumatic brain injury (TBI), which is a major cause of morbidity and mortality in children under 12 years. The goal is to demonstrate that PSH is established as a consequence in children with severe brain trauma. &#x0D; Methodology: Forty articles were found in databases such as LILACS, Elsevier and Scielo that address the theme, excluding those that addressed the TBI in adults and including those that addressed the theme in the pediatric context and published about the PSH, published until the year of 2019.&#x0D; Results: Severe TBI is established as a common cause of hospitalization of children and PSH as a common consequence. Diagnosis and management of this complication require the help of tools such as "PSH-Assessment Measure (PSH-AM)", which has criteria that facilitate the exclusion of other possible causes and guide the treatment. Non-pharmacological therapeutic measures include control of room temperature and low sensory and pharmacological stimuli to deal with symptoms, such as drugs such as opioids, gabaergic agonists, benzodiazepines and adrenergic antagonists. &#x0D; Conclusion: Severe TBI, a common pediatric emergency, can be considered a predictor of PSH. Even though there is no consensus on the diagnosis, PSH-AM proves to be a reliable alternative to professionals dealing with conditions that may or may not correspond with post trauma dysautonomia. This makes it possible to determine not only the child's clinical condition but also the best therapy to apply.