Hypoxia in human NT2-N neurons : The role of acidosis, mitochondria and inflammation

Approximately 4 million infants out of 130 million worldwide annual births suffer from birth asphyxia. Of these, approximately 25% die and 25% develop some kind of neurological sequelae (UNICEF 2003). In the western part of the world, 2-6/1000 of all newborn are diagnosed with HIE, hypoxic ischemic encephalopathy, during the first days of life, due to reduced gas exchange through placenta or lungs. The overall aim for this thesis in pediatric neurology was to understand more about the mechanisms behind hypoxic-ischemic brain damage, so that treatment for this important condition hopefully can be improved. We focused our research on acidosis, mitochondrial function and inflammation, all important but not fully understood phenomena in hypoxic-ischemic brain damage and all possibly amendable to interventional treatment. Hypoxia studies were done in NT2-N neurons, a human cell line consisting of postmitotic, differentiated fenotypic neurons. Analyses were done for cell death, energy level, mitochondrial function and different mediators of inflammation. Acidosis was confirmed to have a protective effect during hypoxia and a detrimental effect early during reoxygenation. Further, an early decline in mitochondrial function was found. Inflammation played a role during hypoxic-ischemic brain damage. Finally, the results showed neuronal damage to occur several hours after the insult. This “delayed” cell death gives the possibility of beneficial intervention during this “therapeutic time window”

Current Trends in Incubator Control for Premature Infants with Artificial Intelligence Based on Fuzzy Logic Control: Systematic Literature Review

Incubator Control for Premature Babies has benefited greatly from the development of creative methods and uses of artificial intelligence. Due to the immaturity of the epidermis, premature infants lose fluid and heat early in life, which causes hyperosmolar dehydration and hypothermia. Water loss through the epidermis. Therefore, in order to maintain the baby's healthy temperature, an incubator is required. As a result, it is anticipated that the baby will maintain the same temperature as in the mother's womb. A temperature regulation system with good measurement and regulation quality is necessary due to the necessity of Incubator Control for Premature Infants with Artificial Intelligence Based on Fuzzy Logic in treating premature infants. The purpose of this research is to assess current trends in artificial intelligence-based fuzzy logic incubator control for preterm infants. The Preferred Reporting Items for Systematic Review (PRISMA) were used in this study's systematic literature review. 188 suitable articles that fit the inclusion requirements were found after the articles were screened and chosen. The outcomes demonstrated that the Incubator Control for Premature Infants offered the best environment for newborns with growth or disease-related issues (premature babies). An incubator is a sealed space free of dust and bacteria with the ability to regulate temperature, humidity, and oxygen to maintain a stable environment

Brain intracellular pH in neonatal encephalopathy

Neonatal encephalopathy following hypoxia-ischaemia occurs in 1-3 per 1000 term births in the UK. Despite therapeutic hypothermia only around 30% survive with normal neurodevelopmental function. Novel, safe, and effective therapies to optimise neuroprotection following neonatal brain injury are needed. The aim of the studies undertaken by the author is to improve the understanding of the role of brain intracellular pH (pHi) in the pathophysiology of brain injury in neonatal encephalopathy to further develop neuroprotective therapies. The first study (Chapter 3) analyses localised deep grey matter (DGM) pHi using phosphorus-31 spectroscopy, obtained within the first two weeks of life in 43 newborn infants with neonatal encephalopathy who underwent cooling. We observed that brain alkalosis is associated with other prognostic factors, such as severity of brain injury on magnetic resonance imaging (MRI), amplitude electroencephalography (aEEG) background pattern, seizure burden measured from raw EEG, and peak-area ratio Lactate+Threonine to N-acetyl aspartate (LacT/NAA) calculated from thalamic proton magnetic resonance spectroscopy (MRS) – current biomarker of outcome. We observed an association between an alkaline DGM pHi on day 2-15 and seizure burden. Previous research in a rodent model showed that both seizure burden and outcome improved when this rebound alkalosis was avoided (e.g., graded restoration of normocapnia or blocking the Na+/H+ exchangers). In a sub-study (Chapter 4), we also observed a trend of increased DGM perfusion (measured using pseudo-continuous arterial spin labelling (pCASL)) and DGM alkaline pHi between day 4-15 in 23 infants. ‘Luxury perfusion’ may be one of the mechanisms leading to brain alkalosis and neuronal damage. A third study (Chapter 5), in a pre-clinical model of neonatal encephalopathy, showed an association between the lowest level of brain tissue acidosis during hypoxia-ischaemia, the duration of acidosis under a certain threshold and its rate of recovery over the first hour after the insult and energy metabolite ratios at 1h after the insult

Investigation of the performance of an automatic arterial oxygen controller

Premature infants often require respiratory support with a varying concentration of the fraction of inspired oxygen (FiO2) to keep the arterial oxygen saturation (SpO2) within the desired range to avoid both hypoxemia and hyperoxemia. Currently, manual adjustment of FiO2 is the common practice in neonatal intensive care units (NICUs). The automation of this adjustment is a topic of interest. The research team, at University of Missouri-Columbia (UMC), has developed a novel automatic arterial oxygen saturation controller. In this study, a systematic approach has been developed to investigate both non-clinical and clinical performance of this device. The non-clinical investigation of the performance was performed using a neonatal respiratory model (hardware-in-the-loop test). A factorial experimental design was utilized to generate challenging model responses of SpO2, which were addressed by the controllers. With this study, we demonstrate the stability and ability of the adaptive PI-controller to improve oxygen saturation control over manual control by increasing the proportion of time where SpO2 of the neonatal respiratory model was within the desired range and by minimizing the variability of the SpO2. In addition, the controller ability to significantly reduce the number of hypoxemic events of the neonatal respiratory model was reported. Results of this investigation show the competence of the controller estimation system for estimating neonatal respiratory model parameters while the adaptive PI-controller was in use. Also, the functionality of the controller with no mechanical or communication failure was validated non-clinically before heading forward to the clinical trial. The clinical investigation of the performance was performed by conducting a clinical trial at the NICU of the MU Women's and Children's Hospital. The crossover design was used for the clinical trial to allow within-subject comparison and to eliminate interpatient variability. Two human subjects, with two different target ranges of SpO2, were enrolled in the study. The adaptive automatic PI-controller shows clinical feasibility to improve the maintenance of SpO2 within the intended range. With this study, we demonstrate the potential of the automatic controller to minimize the variability of SpO2. In addition, the controller shows the ability to reduce the bradycardia and the hypoxemia. Moreover, the hardware and software of the controller show an ability to transition from manual to automatic mode, and vice versa with no pronounced “bump” or step variation in the control signal, and stability and performance were not adversely affected during the transitions.Includes bibliographical reference

The Special Care Nursery

Providing services to high-risk infants and their families in the neonatal intensive care unit is a complex subspecialty of pediatric physical therapy requiring knowledge and skills beyond the competencies for entry into practice. The newborns in the neonatal intensive care unit (NICU) are among the most fragile patients that physical therapists will treat, and detrimental effects can occur as the result of routine caregiving procedures. Pediatric physical therapists (PTs) need advanced education in areas such as early fetal and infant development; infant neurobehavior; family responses to having a sick newborn; the environment of the NICU, physiologic assessment and monitoring; newborn pathologies, treatments, and outcomes; optimal discharge planning; and collaboration with the members of the health care team.256 This chapter describes the neonatal intensive care unit and the role of the physical therapist within this setting. Practice in this setting requires knowledge of neonatal physiology, development, and health complications including prematurity, pulmonary conditions, neurologic conditions, fetal alcohol syndrome, fetal abstinence syndrome, and pain. A framework for physical therapy examination, evaluation, prognosis, and interventions for infants in the special care nursery is presented. The follow-up of infants after discharge from the intensive care nursery is addressed. Two case studies are presented to apply knowledge to practice

Physiological responses of preterm infants in the neonatal intensive care unit to repeated stressors: moderating effect of skin-to-skin care

Technological advances in neonatal care have resulted in a dramatic rise in the survival rate of premature infants. However, knowledge is limited regarding the preterm infant\u27s stress reactivity and the most effective methods to reduce the stress response. This research was designed to investigate stress reactivity in preterm infants and to determine the effect of the intervention strategy of Skin-to-Skin Care (SSC) on the stress response. Twelve preterm infants meeting eligibility criteria established by the approved guideline for SSC in a level HI neonatal intensive care unit (NICU) participated in this study. The cardiopulmonary parameters of heart rate, blood pressure, and respiratory rate were monitored. Adrenocortical responses were determined by changes in levels of concentration of salivary cortisol. Stress reactivity was determined by changes in cardiopulmonary parameters and adrenocortical responses to an invasive stressor, defined in this study as a routine heelstick procedure. Stress reactivity was evaluated under the following test conditions: baseline measures of dependent variables in bed, SSC without invasive stressor, invasive stressor in bed, and invasive stressor in SSC. Changes in the values of the cardiopulmonary parameters and salivary cortisol concentration levels indicated that the preterm infants regulated their responses to aversive stressors differently when they were in SSC than when they were not in SSC. The differences found under these test conditions supported the research hypotheses that providing organizing postural support during SSC reduces stress reactivity in preterm infants in the NICU as reflected by changes in adrenocortical function. Significant changes in cardiopulmonary measures were not demonstrated. The results of this study improved understanding of the mechanism undergirding the process of co-regulation. The clinical implications provide valuable information for medical professionals challenged to implement care in the NICU in a way that reduces destabilizing stress responses of premature infants to the repeated intrinsic and extrinsic stressors experienced during the hospitalization period following a premature birth