Spatial light interference microscopy (slim) measurements of hypothermia in an experimental cellular model of traumatic brain injury

Current neuroscience research conceptualizes the brain as a dynamic, complex cellular network whose connections are constantly changing as we progress through life. Traumatic Brain Injury (TBI) is a disruption in normal brain function following a sudden, external, physical force to the brain parenchyma. TBI is a leading cause of mortality and morbidity among civilians and military personnel worldwide. According to the Centers for Disease Control (CDC) there were over 69,000 TBI-related deaths in the United States in 2021. This equals approximately 190-TBI-related deaths every day. Therefore, it is crucial to understand the ways in which healthy and damaged central nervous system (CNS) cells flourish, that is grow, arborize, link, communicate, and repair. Despite several decades of research, no curative therapies for TBI-associated neurological, behavioral, and cognitive deficits exist. Both the underlying pathobiology and the identification of exploitable neural repair mechanisms need to be more fully investigated; specifically, at the secondary brain injury, since this stage is thought to be responsible for the appearance, progression, and long-term persistence of cognitive, neuropsychiatric, behavioral, and neurological deficits following TBI. Therefore, effective TBI models of disease and standardized quantitative assessment measures for TBI are imperative for testing TBI therapeutics and to facilitate successful TBI drug discovery in this stage. My Ph.D. training has been centered around quantifying neuronal biophysical changes in a Fluid Percussion Instrument (FPI) cellular model of brain injury. This dissertation reviews my research endeavors here at the University of Illinois at Urbana Champaign. First, we examine healthy neurons, and neural network dynamics with a novel Quantitative Phase Imaging (QPI) technique called Spatial Light Interference Microscopy (SLIM). In my first study, I observed that neurons display a significantly higher rate of neurite length growth under lower confluence conditions especially with faster axonal growth and more dynamic changes of dendritic growth over time. In higher confluence conditions, neuronal network also depicted ‘contact inhibition’ which shows slower or no growth over time. SLIM is an ideal imaging technique to study FPI induced neuronal damage to represent TBI because it provides time-lapse imaging of living cells over weeks while preserving cell viability. SLIM allows for the measurement of FPI-induced changes in neuronal survival and iii health overtime, and for the investigation of Therapeutic Hypothermia (TH) efficacy following TBI. Through these biophysical measurements from SLIM, we examined the effects of TH on FPI-induced injury on murine cortical neurons. We found that a five-hour treatment period of 32°C TH, administered within 2 hours of injury was optimally beneficial to cortical neurons in vitro following mild and moderate FPI, from less than 40% to 80% of live cell survivability. We didn’t find any beneficial effects of 32°C TH when it is administered before FPI injury. These findings may act as a springboard for standardizing future in vitro TBI therapeutic investigational studies to support the development of successful TBI therapeutics and furthermore to in vivo and clinical TBI studies.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Neuroscience

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2023

Author dc:creator

• Lee, Young Jae

Contributors dc:contributor

• Best-Popescu, Catherine
• Chung, Hee Jung
• Yoo, Dongwan
• Allen, Jont

• Traumatic Brain Injury
• Tbi
• Spatial Light Interference Microscopy
• Slim
• Fluid Percussion Injury
• Fpi
• Hypothermia
• Therapeutic Hypothermia
• Th
• Quantitative Phase Imaging
• Qpi
• Dispersion-relation Phase Spectroscopy
• Dps
• Dry Mass

Statement dc:rights

• Copyright 2023 Young Jae Lee

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/121500

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F121500