Tissue Oxygenation Dynamics During Seizure to Spreading Depression Transition in Rat Brain
Open Access
- Author:
- Liu, Jiayang
- Graduate Program:
- Engineering Science and Mechanics
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- April 27, 2021
- Committee Members:
- Bruce Gluckman, Dissertation Advisor/Co-Advisor
Bruce Gluckman, Committee Chair/Co-Chair
Corina Stefania Drapaca, Committee Member
Patrick James Drew, Committee Member
Mehdi Kiani, Outside Member
Albert Eliot Segall, Program Head/Chair - Keywords:
- Tissue oxygenation
spontaneous seizure
spreading depolarization
extracellular space volume
effective diffusion coefficient - Abstract:
- To carry out different kinds of brain activities, neurons in the brain need a continuous supply of energy stored in the form of adenosine triphosphate (ATP). Neurons generate ATP by the process of oxidative phosphorylation in the mitochondria requires continuous, sufficient availability of oxygen. Thus a proper regulation of the brain tissue oxygenation is critical for neurons survival and health. Epilepsy is one of the most common neurological disorders and is characterized by spontaneous, recurrent seizures. The occurrence of this spontaneous, recurrent epileptic seizure is a major human health concern, leading to a significant deficit in the quality of life, higher mortality, and significant economic impact. Spreading depression (SD) is a neurophysiological phenomenon and characterized by a slow-propagating wave of suppressed neuronal activity associated with sustained depolarization of neurons and glial cells. It leads to loss of electrical activity, changes in the synaptic architecture, and an altered vascular response. SD plays an important role in a range of other neurological disorders such as migraine and stroke. Researchers have demonstrated that epileptic seizures are frequently accompanied by SD. To study the tissue oxygenation dynamics during epileptic seizures and seizures associated SD, we introduced a low-cost epilepsy monitoring unit (EMU) that has a scalable architecture and can provide high-fidelity, DC-sensitive biopotential recordings and fulfill oxygen sensing using different kinds of voltammetric methods with a built-in electrochemical instrument (EI). We applied the EMU to freely moving rats prepared under the tetanus toxin (TeTX) model of temporal lobe epilepsy (TLE) and demonstrated long-term, 24/7 continuous epileptic seizures, and co-occurrent SD recordings along with tissue oxygenation monitoring. We characterized the tissue oxygenation during normal transitions, peri-seizure transition and the seizure to SD transition. We further extracted the effect of the effective oxygen diffusion coefficient (Deff ) from the tissue oxygenation, characterized it during these transitions, and related it to the extracellular space volume change. This work elevates the understanding of the role of tissue oxygenation during the spontaneous seizure to SD transition.