Temporal expression pattern of cytokines and other markers of brain injury in term infants with hypoxic ischemic injury

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dc.contributor.advisorEsser, Michael J.
dc.contributor.authorGoswami, Ipsita Roy
dc.contributor.committeememberMineyko, Aleksandra
dc.contributor.committeememberPittman, Q. J.
dc.contributor.committeememberYusuf, Kamran
dc.contributor.committeememberKhorshid, Mohammad
dc.date2018-11
dc.date.accessioned2018-09-18T20:40:44Z
dc.date.available2018-09-18T20:40:44Z
dc.date.issued2018-09-13
dc.description.abstractHypoxic Ischemic Encephalopathy (HIE) is the most common cause of perinatal brain injury. Treatment is available, therapeutic hypothermia (TH), but reliable tools are needed to determine early after birth who will benefit most. Cytokines, as indicators of brain injury, are potential biomarkers and are best studied by understanding network changes. This study sought to identify the cytokine molecular signatures associated with abnormal MRI or death in neonates with HIE. Multiplex immunoassay was used to quantify cytokine levels at multiple timepoints from birth to 96 hours of life. Machine learning algorithms were used for pattern identification to gain mechanistic insights. Cord blood levels of IL-6, IFNγ, IL-1ra, G-CSF, FGF-b and MCP-1 were significantly elevated in neonates with HIE compared to controls. Neonates with abnormal MRI or death had elevated cord blood IL-10 and MCP1 levels, high serum IL1ra and G-CSF levels at 24 hours, and low PDGF and IP10 levels at all time points. Further, in neonates with adverse outcomes IL-10, G-CSF, MCP1, IL-6, TNF-α, IL-8, and IL-1ra levels were elevated, while IL-4, PDGF, MIP1a, IL-15, IP10, and IFN-γ were lower at all time points. Conversely, the combinations of TNF-α levels < 74.4 pg/ml with IL8 levels > 0.85 pg/ml and IFN-γ levels > 0.04 pg/ml in cord blood predicted normal MRI (sensitivity 100%, specificity 37.5%). Similarly, IL-10 levels > 36.7 pg/ml or a combination of IL-6 levels < 8.46 pg/ml and IL-8 levels > 59.5 pg/ml at 24 hours were predictive of unfavorable outcome (sensitivity 95.2%, specificity of 62.5%). Regardless of the encephalopathy grading, TH shifted the cytokine balance towards neurotrophic factors (G-CSF) and Th2 cytokines (IL-4, IL-5, IL-10) around 24 hours of life followed by a reversal towards Th1 cytokines (IL-2, TNF-α and IFN-γ) after termination of TH. This general analysis of the peripheral cytokines in HIE delineates the principal drivers of the cytokine network that may serve as biomarkers. Upregulation of proinflammatory cytokines accompanied by active modulation of anti-inflammatory cytokines could account for the variations in patient-specific innate compensatory response that ultimately characterizes the short-term clinical outcome.en_US
dc.identifier.citationGoswami, I. R. (2018). Temporal expression pattern of cytokines and other markers of brain injury in term infants with hypoxic ischemic injury (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/32936en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/32936
dc.identifier.urihttp://hdl.handle.net/1880/107760
dc.language.isoeng
dc.publisher.facultyCumming School of Medicine
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectHypoxic Ischemic Encephalopathy
dc.subjectPerinatal Asphyxia
dc.subjectNeuroinflammation
dc.subjectCytokines
dc.subjectNeurodevelopmental Outcome
dc.subject.classificationNeuroscienceen_US
dc.subject.classificationBiophysics--Medicalen_US
dc.subject.classificationImmunologyen_US
dc.titleTemporal expression pattern of cytokines and other markers of brain injury in term infants with hypoxic ischemic injury
dc.typemaster thesis
thesis.degree.disciplineNeuroscience
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
ucalgary.item.requestcopytrue
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