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Ikonomidou Lab

Ikonomidou Lab

Hrissanthi "Chris" Ikonomidou, M.D., Ph.D.
Hrissanthi “Chris” Ikonomidou, M.D., Ph.D.

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. Her team wants to explore the potential of direct current stimulation and cognitive training to improve cognitive skills in MCI and intellectual disabilities.

Detection of cell death in the developing brain

It is well established that exposure of immature animals of several species, including non-human primates, to sedative/anesthetic drugs (SADs) and antiepileptics (AEDs), 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 and/or AEDs at doses that induce apoptotic injury in the developing animal brain.  The human epidemiological evidence is considered inconclusive (too many inadequately controlled variables), so it remains debatable whether the developing human brain is susceptible to anesthesia- and AED-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, Dr Ikonomidou and her collaborators, Drs Ivan Rosado Mendez and Dr Timothy Hall (Medical Physics) are working on developing and optimizing quantitative ultrasound for detecting and evaluating the severity of brain injuries in neonatal non-human primates and human infants.

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.

Hypothermia is successfully applied in neonatal and pediatric medicine to minimize brain injury from perinatal asphyxia, cardiac surgery and neonatal stroke. This project investigates hypothermia as a potential protective treatment of the developing primate brain against histological, behavioral and neurocognitive toxicity of anesthetic, sedative and anticonvulsant drugs. Research is being conducted in NHP infants using clinically relevant drug combinations and durations of treatment.

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 are enrolling 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 in blood and cerebrospinal fluid indicative of cell death of neurons and glia and synaptic toxicity.

Cerebrospinal Fluid Biomarkers in Childhood Leukemias
Ikonomidou C.
Cancers (Basel). 2021 Jan 24;13(3):438. doi: 10.3390/cancers13030438.
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Brain pathology caused in the neonatal macaque by short and prolonged exposures to anticonvulsant drugs
Noguchi KK, Fuhler NA, Wang SH, Capuano S 3rd, Brunner KR, Larson S, Crosno K, Simmons HA, Mejia AF, Martin LD, Dissen GA, Brambrink A, Ikonomidou C.
Neurobiol Dis. 2021 Feb;149:105245. doi: 10.1016/j.nbd.2020.105245. Epub 2020 Dec 29.
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Optimization of Ultrasound Backscatter Spectroscopy to Assess Neurotoxic Effects of Anesthesia in the Newborn Non-human Primate Brain
Castañeda-Martinez L, Noguchi KK, Ikonomidou C, Zagzebski JA, Hall TJ, Rosado-Mendez IM.
Ultrasound Med Biol. 2020 Aug;46(8):2044-2056. doi: 10.1016/j.ultrasmedbio.2020.04.004. Epub 2020 May 29.
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Amplitude-integrated EEG use in neonatal abstinence syndrome: a pilot study
Limjoco J, Zawadzki L, Belden M, Eickhoff J, Ikonomidou C.
J Matern Fetal Neonatal Med. 2020 Nov;33(21):3565-3570. doi: 10.1080/14767058.2019.1579190. Epub 2019 Mar 1.
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Isobaric Multiplex Labeling Reagents for Carbonyl-Containing Compound (SUGAR) Tags: A Probe for Quantitative Glycomic Analysis
Feng Y, Chen B, Yu Q, Zhong X, Frost DC, Ikonomidou C, Li L.
Anal Chem. 2019 Feb 19;91(4):3141-3146. doi: 10.1021/acs.analchem.8b05757. Epub 2019 Feb 4.
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Non-functionalized soft alginate hydrogel promotes locomotor recovery after spinal cord injury in a rat hemimyelonectomy model
Sitoci-Ficici KH, Matyash M, Uckermann O, Galli R, Leipnitz E, Later R, Ikonomidou C, Gelinsky M, Schackert G, Kirsch M.
Acta Neurochir (Wien). 2018 Mar;160(3):449-457. doi: 10.1007/s00701-017-3389-4. Epub 2017 Dec 11.
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AMPA Receptor Antagonist CFM-2 Decreases Survivin Expression in Cancer Cells
Ruiz DS, Luksch H, Sifringer M, Temme A, Staufner C, Rzeski W, Marzahn J, Grabarska A, Ikonomidou C, Stepulak A.
Anticancer Agents Med Chem. 2018;18(4):591-596. doi: 10.2174/1871520618666180228123406.
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Riluzole Inhibits Proliferation, Migration and Cell Cycle Progression and Induces Apoptosis in Tumor Cells of Various Origins
Lemieszek MK, Stepulak A, Sawa-Wejksza K, Czerwonka A, Ikonomidou C, Rzeski W.
Anticancer Agents Med Chem. 2018;18(4):565-572. doi: 10.2174/1871520618666180228152713.
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Chemotherapy and the pediatric brain
Ikonomidou C.
Mol Cell Pediatr. 2018 Nov 6;5(1):8. doi: 10.1186/s40348-018-0087-0.
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Autoimmune Ataxia During Maintenance Therapy for Acute Lymphoblastic Leukemia
Voeller J, Ikonomidou C, Brucker J, Diamond C, Frierdich S, Patel N.
Child Neurol Open. 2018 Dec 16;5:2329048X18819235. doi: 10.1177/2329048X18819235. eCollection 2018.
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