Acute Cellular and Behavioral Outcomes of Focal Impact Traumatic Brain Injury in Xenopus laevis

dc.contributor.advisorSater, Amy K.
dc.contributor.committeeMemberDauwalder, Brigitte
dc.contributor.committeeMemberAlward, Beau A.
dc.contributor.committeeMemberLekven, Arne C.
dc.creatorSpruiell Eldridge, Sydnee Lea
dc.creator.orcid0000-0001-9600-5946
dc.date.accessioned2023-06-02T18:18:06Z
dc.date.createdDecember 2022
dc.date.issued2022-11-28
dc.date.updated2023-06-02T18:18:08Z
dc.description.abstractTraumatic brain injury (TBI) is one of the leading causes of mortality and disability throughout the world. The Centers for Disease Control and Prevention estimate that up to 5.3 million people in the United States are living with a TBI-related disability, including cognitive, behavioral, and functional limitations. Although TBI represents a significant public health concern, we currently lack effective therapies to promote repair and recovery in the brain. TBI is a complex condition; characterized by an initial insult which sets in motion a secondary injury cascade including neuroinflammation, blood-brain barrier disruption, edema, and reactive astrogliosis. Reactive astrogliosis occurs on a finely graded continuum, encompassing both the initiation of essential recovery mechanisms and exacerbating inflammation. As it has been linked to chronic neurodegenerative diseases, TBI represents the initiation of a disease process, rather than an isolated event. While the initial insult causes irreversible damage, secondary injury begins minutes after and can last for years, presenting a promising opportunity for therapeutic intervention. We begin by investigating the response to focal impact injury in the optic tectum of Xenopus laevis tadpoles. This injury disrupts the blood-brain barrier, causing edema, and produces deficits in visually-driven behaviors. Injured brains show an early transcriptional activation of inflammatory cytokines, followed by astrocytes undergoing morphological alterations and upregulation of genes consistent with reactive astrogliosis. Since our results demonstrate that the response to focal impact injury in Xenopus tadpoles resembles that of mammalian models, we present a new, scalable vertebrate model for TBI. Next, we focus on characterizing the current literature surrounding sex differences in animal models of TBI and presenting preliminary findings in our model. Estrogen and its derivatives have recently been explored for their potentially neuroprotective capabilities. Previous works have suggested that estrogenic compounds are able to regulate reactive astrogliosis, control neuroinflammation, and reduce edema. Since treatment with estrogen comes with significant risk factors, many have suggested the use of selective estrogen receptor modulators (SERMs) like Tamoxifen. Our results support tamoxifen as an effective neuroprotectant when administered after a TBI and demonstrate a successful proof-of-concept pharmacological intervention in our X. laevis model of TBI.
dc.description.departmentBiology and Biochemistry, Department of
dc.format.digitalOriginborn digital
dc.format.mimetypeapplication/pdf
dc.identifier.citationPortions of this document appear in: Spruiell Eldridge, S. L., Teetsel, J. F. K., Torres, R. A., Ulrich, C. H., Shah, V. V, Singh, D., Zamora, M. J., Zamora, S., Sater, A. K. (2022). A Focal Impact Model of Traumatic Brain Injury in Xenopus Tadpoles Reveals Behavioral Alterations, Neuroinflammation, and an Astroglial Response. International Journal of Molecular Sciences, 23(14), 7578.
dc.identifier.urihttps://hdl.handle.net/10657/14402
dc.language.isoeng
dc.rightsThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. UH Libraries has secured permission to reproduce any and all previously published materials contained in the work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).
dc.subjectTraumatic brain injury
dc.subjectXenopus laevis
dc.subjectBiology
dc.subjectNeuroscience
dc.subjectBehavioral biology
dc.subjectAstrocytes
dc.titleAcute Cellular and Behavioral Outcomes of Focal Impact Traumatic Brain Injury in Xenopus laevis
dc.type.dcmiText
dc.type.genreThesis
dcterms.accessRightsThe full text of this item is not available at this time because the student has placed this item under an embargo for a period of time. The Libraries are not authorized to provide a copy of this work during the embargo period.
local.embargo.lift2024-12-01
local.embargo.terms2024-12-01
thesis.degree.collegeCollege of Natural Sciences and Mathematics
thesis.degree.departmentBiology and Biochemistry, Department of
thesis.degree.disciplineBiology
thesis.degree.grantorUniversity of Houston
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

Files

License bundle

Now showing 1 - 2 of 2
No Thumbnail Available
Name:
PROQUEST_LICENSE.txt
Size:
4.44 KB
Format:
Plain Text
Description:
No Thumbnail Available
Name:
LICENSE.txt
Size:
1.82 KB
Format:
Plain Text
Description: