ORCID
https://orcid.org/0000-0003-4816-8139
Date of Award
2024
Document Type
Dissertation
Degree Name
Philosophy (Ph.D)
Department
Pharmaceutical Sciences
First Advisor
Francis X. Schanne
Abstract
The dendritic cells of the CNS, the microglia (MG), are an initiation point of the immunological response within the post blood-brain barrier (BBB) compartment. Microglia morphology drastically changes in response to cell stress to a much different non-dendritic morphology. This investigation postulates that if the first MG responses to toxic injury are isolated and studied in greater morphological detail there is much to be learned about MG metamorphosis from a baseline (M2) to an activated (M1) state. The organotypic hippocampal slice was the experimental setting used to investigate microglial response to toxic injury. This isolates dendritic cellular responses and associated post-BBB cells dynamics from the impact of nonspecific of in-vivo blood-derived factors. Within the context of biochemically verified precise toxic cell injury/death (induced with mercury or cyanide in combination with 2-deoxy-glucose) to a specific region within a cultured hippocampal slice, MG’s morphological response near and distal to the site of toxicological insult was evaluated. There was up to 35% increase in MG activation proximally to injury (CA3 region) and no changes distally (DG region) when compared to control slices treated with PBS. Maximum MG activation consisted of a 3 plus-fold increase in the distance between the nucleus membrane and the cell membrane, which underscores an extensive and quantifiable amount of membrane rearrangement. In between baseline and activated MG morphologies, 5 intermediate morphologies (or morphological variations) are described as it relates to its cell body, nucleus, and dendrites. The result from this study reconciles details of MG’s structure to its holistic characteristics in relation to parenchymal cell stress within a cultured CNS tissue sample.
Recommended Citation
Trejos, Jesus Antonio, "EVALUATION OF MICROGLIA’S STRUCTURAL VARIATIONS WITHIN AN ORGANOTYPIC HIPPOCAMPAL SLICE MODEL AFTER REGIONALIZED TOXIC INJURY" (2024). Theses and Dissertations. 819.
https://scholar.stjohns.edu/theses_dissertations/819