Chris Ikonomidou Lab
Dr Ikonomidou is a physician researcher who wants to develop therapies for neurodevelopmental disorders. Her research focuses on exploring how the developing brain reacts to environmental insults and finding ways to protect it. The goal is to help optimize therapeutic interventions in infants born prematurely, infants, children and adults with brain injuries, seizures, neurodevelopmental disorders or cancer.
More recently Dr Ikonomidou has developed interest in neuromodulation and its potential application in treatment of intellectual disabilities. Her team wants to explore the potential of direct current stimulation in cognitive enhancement in children with intellectual disabilities.
Ongoing Research Projects:
Detection of apoptosis in the developing primate brain
It is well established that exposure of immature animals of several species, including non-human primates, to sedative/anesthetic drugs (SADs), at clinically relevant doses, causes apoptotic death of brain cells and long-term neurodevelopmental impairment. Numerous recent human studies have documented that exposure of human infants to brief anesthesia is associated with a significant increase in risk for long-term neurodevelopmental impairment. Millions of human fetuses and infants, including premature infants, are exposed every year to SADs at doses that induce apoptotic injury in the developing animal brain. The human epidemiological evidence, although generated by highly competent researchers, is considered inconclusive (too many inadequately controlled variables), so it remains debatable whether the developing human brain is susceptible to anesthesia-induced injury. Methods used in animal research to document the brain damaging properties of SADs are invasive and cannot be used in human research. We need new research approaches that are reliable and can non-invasively address and answer the human susceptibility and related questions. To meet this need, we want to develop non-invasive neuroimaging methods for detecting and evaluating the severity of SAD-induced brain injury.
Methods to study chemotherapy-related neurotoxicity in children
Survival rates of children with cancer are steadily increasing and this urges attention to neurocognitive and psychiatric outcomes, as these markedly influence quality of life in these children. Neurobehavioral morbidity in childhood cancer survivors affects diverse aspects of cognitive function, attention, memory, processing speed, intellect (IQ), academic achievement and emotional health.
The goal of this project is to prospectively characterize the evolution of biochemical features of chemotherapy-induced CNS toxicity in children. We will enroll children undergoing systemic and CNS directed chemotherapy for low, average and high risk B-cell-ALL. Goal is to explore and characterize changes in neurochemical biomarkers indicative of apoptotic and excitotoxic cell death of neurons and glia in blood and cerebrospinal fluid.
Phase I Trial of the Feasibility and Dose Tolerability of High Definition Transcranial Direct Current Stimulation in healthy adults and adults with Down Syndrome
Down syndrome (trisomy 21, OMIM #190685) is a genetic disorder which leads to mental retardation (MR) in all affected individuals.
Transcranial direct current stimulation (tDCS) is a method which enables noninvasive electrical stimulation of the cortex via electrodes placed on the skull. High definition tDCS (HD-tDCS) allows for precise generation of electrical fields over selected cortical areas using multiple electrodes. The purpose of this pilot trial is to study feasibility, tolerability, and safety of HD-tDCS administered daily for 20 sessions to human subjects.
- To assess feasibility and tolerability of HD-tDCS, administered up to 5 days per week for a total of 20 sessions in healthy adult subjects;
- To assess feasibility and tolerability of HD-tDCS, administered up to 5 days per week for a total of 20 sessions in adult subjects with Down Syndrome.
Novel Imaging Mass Spectrometry-based Proteomics Technology to Identify Autism Biomarkers
Autism spectrum disorders (ASD) are neurobehavioral syndromes with a prevalence of 1:68 in children. Evidence supports the hypothesis that, although pathogenetically different, ASD share common dysfunctional mechanisms and pathways which, unfortunately, remain largely unknown. We hypothesize that proteins and peptides which play a key role in the pathogenesis of autism demonstrate similar regional and age-dependent expression patterns in the brain in different syndromes of autism, and differ from those expressed in normal brains. Such proteins/peptides can be useful as biomarkers for early identification of individuals at risk for developing ASD, and some may even constitute novel therapeutic targets. We are exploring this hypothesis by combining novel high resolution proteomics methodologies and gene expression technology with behavioural, pharmacological and neuropathological studies in established mouse models of autism.
Hypothermia to Prevent Neurotoxic Effects of Pediatric Drugs
The goal of this project is to study whether hypothermia protects the nonhuman primate brain from histological and behavioral toxicity of anesthetics, sedatives and antiepileptics.
Pediatric drugs which are used as anesthetics, sedatives and antiepileptics in neonatal and pediatric medicine, can be harmful to the developing brain. They have been shown to cause widespread cell death, impair synaptic maturation and plasticity and inhibit neurogenesis (the birth of new nerve cells) in the brains of rodents and non-human primates (NHP). Studies in rodents and in NHPs have provided compelling evidence that early life exposure to these drugs also triggers behavioral toxicity, i.e. causes long term behavioral and cognitive deficits that persist when the animals mature. Furthermore, retrospective clinical studies raise serious concerns that exposure of human infants to these classes of drugs may lead to neurocognitive and behavioral disorders.
Practicing medicine without anesthetics, sedatives and antiepileptics is impossible. These medications must be used during surgeries, prolonged sedation during critical illness, and for the treatment of seizures. Thus, the crucial question arises whether protective measures can be developed and applied in the clinical setting to avoid potential iatrogenic adverse effects of these classes of drugs on brain health and subsequent development in the most vulnerable age groups, specifically neonates and infants during the first year of life.
Hypothermia is successfully applied in neonatal and pediatric medicine to minimize brain injury from perinatal asphyxia, cardiac surgery and neonatal stroke. We propose to investigate hypothermia as a potential protective treatment of the developing primate brain against histological, behavioral and neurocognitive toxicity of anesthetic, sedative and anticonvulsant drugs. Research will be conducted in NHP infants using clinically relevant drug combinations and durations of treatment. We plan to use sevoflurane (SEVO), which is becoming one of the most frequently used general anesthetics in pediatric medicine and the combination of phenobarbital and midazolam (Pb/M), a protocol commonly used for sedation or antiepileptic therapy in neonates and infants. We want to test the following three hypotheses: (1) Exposure of NHP infants to SEVO anesthesia for 5 hrs will cause death (apoptosis) of brain cells, and application of hypothermia throughout the duration of anesthesia and for 1 hr thereafter will prevent or reduce the severity of this injury; (2) Application of hypothermia during and 12 hrs after exposure of NHP infants to a 24 hr long treatment with the antiepileptic/sedative drug combination phenobarbital/midazolam (Pb/M) will prevent or mitigate the acute cell death (apoptosis) response caused by the drugs; (3) Exposure of NHP infants to the drug combination Pb/M for 24 hours will cause long-term neurobehavioral impairment (NBI), and application of hypothermia throughout the duration of Pb/M treatment and for 12 hrs thereafter (the period during which the drugs are still present at toxic concentrations in the brain) will prevent or mitigate the long-term NBI. These questions cannot be answered by research on human subjects, but can be successfully addressed and answered by research using non-human primates.