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The Roles of TRP Channels in Ischemi...

Hancock, Dominique Aerin.

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The Roles of TRP Channels in Ischemic and Cold Spreading Depolarization.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The Roles of TRP Channels in Ischemic and Cold Spreading Depolarization./
作者:	Hancock, Dominique Aerin.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2023,
面頁冊數:	105 p.
附註:	Source: Masters Abstracts International, Volume: 85-04.
Contained By:	Masters Abstracts International85-04.
標題:	Cold. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30616940
ISBN:	9798380487092

The Roles of TRP Channels in Ischemic and Cold Spreading Depolarization.
Hancock, Dominique Aerin.

The Roles of TRP Channels in Ischemic and Cold Spreading Depolarization. - Ann Arbor : ProQuest Dissertations & Theses, 2023 - 105 p.

Source: Masters Abstracts International, Volume: 85-04.

Thesis (M.Sc.)--Queen's University (Canada), 2023.

Spreading depolarization (SD) is a propagating wave of cellular depolarization that traverses through the higher cerebral grey matter, leading to neuronal swelling and injury. SD is caused by the failure of the sodium-potassium activated adenosine triphosphatase (Na+ /K+ATPase) pump. SD occurs in cases such as ischemic stroke where it is shown to expand the region of tissue damage. While it is known that SD is responsible for worsening neurological outcomes after stroke, there are still a lack of pharmaceutical targets. This study focuses on transient receptor potential vanilloid 4 (TRPV4) and transient receptor potential melastatin 8 (TRPM8) to investigate their contribution to SD onset and subsequent damage.TRPV4 inhibition by the selective antagonist, HC-067047, in a brain slice model of ischemic stroke (oxygen and glucose deprivation, OGD) delayed SD onset and slowed SD propagation speed in one mouse strain (C57BL/6) but not the other (CD1(ICR)). There was, however, a reduction in OGD-mediated swelling, measured by a change in light transmittance (DLT), with pre-treatment of the TRPV4 antagonist in both mouse strains. In C57 mice, at 10µM HC-067047, there was a 26% reduction in DLT from control. In CD1 mice 10µM HC-067047 elicited a 25% reduction in DLT from control, 1µM HC-067047 a 42% reduction in DLT, and 0.3µM HC-067047 a 51% reduction in DLT. As well, TRPV4 agonism by GSK1016790A (10µM) delayed SD onset in CD1 mice. Together, this suggests that the TRPV4 channel has a multifaceted role in SD and cell swelling in the ischemic brain.TRPM8 was investigated for its contribution to the generation of cold temperature induced spreading depolarization (cold-SD); however, its specific antagonist PBMC (25nM) did not affect cold-SD initiation, propagation, or subsequent swelling. In our other experiments regarding cold-SD properties, we demonstrated a positive shift in extracellular potential by +2mV mediated by tissue cooling. As well, we showed that cold-SD is a true depolarization event marked by a negative shift in extracellular potential of - 2-4mV coinciding with the imaged cold-SD wavefront. We conclude that cold-SD is evoked by dysfunction of the Na+ /K+ATPase pump caused by the reduction in metabolic rate at near-freezing temperatures.

ISBN: 9798380487092Subjects--Topical Terms:

560283
Cold.

The Roles of TRP Channels in Ischemic and Cold Spreading Depolarization.
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