Biomedical Sciences ETDs

Publication Date

7-8-2024

Abstract

Spreading depolarization (SD) is now established as a critical event contributing to the expansion of acute brain injuries. In areas with insufficient access to metabolites, SD results in episodic glutamate accumulation and NMDA receptor over-activation. Intriguingly, in areas with sufficient access to metabolites SD can result in synaptic strengthening, together suggesting SD consequences may vary widely based on metabolic context. Utilizing acute murine brain slices, this dissertation sought to interrogate the cell and molecular mechanisms of SD induced detriment and revitalization. We describe evidence that the primary NMDAR subtype involved in SD is GluN2A-containing NMDARs, and when targeted during SD can reduce tissue detriment. We also show that SD induces a unique form of intermediate duration potentiation which is transient and results from enhanced excitatory synaptic transmission. These data support SD as 1) resulting in a transient period of hyperexcitability after SD and 2) involving primarily GluN2A-containing NMDARs.

Keywords

plasticity, spreading depolarization, NMDA receptors

Sponsors

The National Institute of Health grants NS106901, P206GM109089 and T32HL007736

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

C. William R. Shuttleworth

Second Committee Member

C. Fernando Valenzuela

Third Committee Member

Nora I. Perrone-Bizzozero

Fourth Committee Member

Russell Morton

Fifth Committee Member

Nikki Jernigan

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