THE THIN LINE BETWEEN LIFE AND DEATH: IMPACT OF A TRANSIENT ISCHEMIC ATTACK ON NEURONAL EXCITABILITY
Date of Award
May 2024
Degree Type
Thesis
Degree Name
Master of Science
Department
Psychology
First Advisor
James R Moyer, Jr.
Committee Members
Karyn Frick, Jeffrey Lopez-Rojas
Abstract
Current reports rank stroke as the fifth leading cause of death in the United States, and the source of life-altering cognitive impairments in survivors. Approximately 87% of reported stroke cases are the result of an ischemic stroke, characterized by the occlusion of an artery that supplies oxygen-rich blood to the brain. Under these pathological conditions, local networks exhibit a change in excitability and homeostatic function, which can influence delayed neuronal death depending on the severity of the insult. However, inconsistent electrophysiological findings justify the need for additional research to uncover the pathophysiology of this destructive neurovascular disease. Given that susceptibility is highest amongst aging women and greatly influenced by a prior transient ischemic attack (TIA), the present study investigated the impact of a TIA on female and male neuronal membrane properties, intrinsic excitability, and structural integrity in a region that is vital for memory formation. Acute coronal brain slices containing the dorsal hippocampus were prepared from adult female and male Fisher 344 rats and placed in oxygenated artificial cerebral spinal fluid (aCSF). Half the slices from each subject underwent 5 min of oxygen-glucose deprivation (OGD) to model a TIA and the other half remained in oxygenated aCSF as a control. Cell death was assayed by trypan blue exclusion, which labels dead and dying neurons, to confirm the effectiveness of the OGD protocol. Neuronal damage was drastically increased in this model, as indicated by a greater number of trypan blue-labeled neurons in OGD-treated slices compared to control-treated slices. To evaluate the impact of OGD on the physiological and morphological properties of CA1 pyramidal neurons, biocytin-filled patch electrodes were used to obtain whole-cell recordings (WCRs) from visually identified CA1 pyramidal neurons from control- and OGD-treated slices. No sex differences were observed in the intrinsic excitability of CA1 neurons under control conditions. However, we observed an increase in action potential frequency of CA1 neurons from female rats following OGD compared to neurons from control slices. In contrast, the intrinsic excitability of male CA1 neurons was similar between conditions. A difference in neuronal membrane properties between female and male rats was also exhibited by sag amplitude and action potential threshold following OGD. These observed changes imply a modulatory role of sex on the intrinsic excitability of hippocampal CA1 pyramidal neurons during a TIA, but the possible maintenance of homeostasis observed in male neurons should not be ignored. These data provide insights into unique mechanisms that may underlie the survival of CA1 hippocampal neurons during a TIA and offers avenues to enhance the restoration of both neuronal and cognitive functioning.
Recommended Citation
Natwora, Brendan, "THE THIN LINE BETWEEN LIFE AND DEATH: IMPACT OF A TRANSIENT ISCHEMIC ATTACK ON NEURONAL EXCITABILITY" (2024). Theses and Dissertations. 3499.
https://dc.uwm.edu/etd/3499