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The Glycolytic Inhibitor 2-Deoxygluc...

Koenig, Jenny Bryne.

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The Glycolytic Inhibitor 2-Deoxyglucose as a Novel Therapeutic Agent to Prevent Cortical Network Dysfunction after Traumatic Brain Injury.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The Glycolytic Inhibitor 2-Deoxyglucose as a Novel Therapeutic Agent to Prevent Cortical Network Dysfunction after Traumatic Brain Injury./
作者:	Koenig, Jenny Bryne.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
面頁冊數:	161 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Contained By:	Dissertations Abstracts International81-04B.
標題:	Neurosciences. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13810534
ISBN:	9781687910462

The Glycolytic Inhibitor 2-Deoxyglucose as a Novel Therapeutic Agent to Prevent Cortical Network Dysfunction after Traumatic Brain Injury.
Koenig, Jenny Bryne.

The Glycolytic Inhibitor 2-Deoxyglucose as a Novel Therapeutic Agent to Prevent Cortical Network Dysfunction after Traumatic Brain Injury. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 161 p.

Source: Dissertations Abstracts International, Volume: 81-04, Section: B.

Thesis (Ph.D.)--Tufts University-Graduate School of Biomedical Sciences, 2021.

This item must not be sold to any third party vendors.

Traumatic brain injury (TBI) is a significant cause of disability worldwide, as it can cause a wide range of chronic complications associated with disrupted cortical function. Multiple molecular, cellular, and network pathologies occur following injury, but the pathophysiology of post-TBI cortical dysfunction is not well-understood. Many studies have demonstrated that GABAergic inhibitory network function is compromised following TBI, which may contribute to cortical hyperexcitability and motor, behavioral, and cognitive deficits. The loss or dysfunction of inhibitory interneurons may also be epileptogenic, and thus, could result in spontaneous new-onset seizure activity observed commonly after TBI, in a condition known as post-traumatic epilepsy (PTE). Preserving the function of GABAergic interneurons, therefore, is a rational therapeutic strategy to preserve cortical function after TBI and prevent long-term clinical complications. Following TBI, there is a complex landscape of metabolic changes that evolve over days and weeks. Based on rich clinical and preclinical data of these post-TBI changes in glucose utilization, combined with the success of metabolic therapies like the ketogenic diet in treating epilepsy, interest has grown in determining whether manipulating metabolic activity following traumatic brain injury may have therapeutic value to prevent post-traumatic epileptogenesis. In this thesis, I explore whether the use of a glycolytic inhibitor, 2-deoxyglucose (2-DG), affects post-TBI cortical pathology. First, I outline the therapeutic rationale behind this approach by examining changes in glucose utilization and glycolytic activity in the brain following traumatic brain injury and during seizures. In this section, I also outline potential paths forward to utilize glycolytic inhibitors as a disease-modifying therapy for post-traumatic epilepsy. Then, I tested whether the use of 2-DG attenuated cortical dysfunction after TBI in a mouse model of focal brain contusion. Employing the controlled cortical impact (CCI) model of TBI, we found that in vitro 2-DG treatment rapidly attenuated epileptiform activity seen in acute cortical slices 3-5 weeks after TBI. One week of in vivo 2-DG treatment immediately after TBI prevented the development of epileptiform activity, restored excitatory and inhibitory synaptic activity, and attenuated the loss of parvalbumin-expressing inhibitory interneurons. Further, I found that acute in vitro application of 2-DG decreased the excitability of excitatory neurons, but not inhibitory interneurons, suggesting a possible cell type-specific mechanism for 2-DG's effects. In summary, the glycolytic inhibitor 2-DG may have therapeutic potential to restore network function following TBI.

ISBN: 9781687910462Subjects--Topical Terms:

588700
Neurosciences.
Subjects--Index Terms:

2-deoxyglucose

The Glycolytic Inhibitor 2-Deoxyglucose as a Novel Therapeutic Agent to Prevent Cortical Network Dysfunction after Traumatic Brain Injury.
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