In Vivo Detection of Extracellular Adenosine Triphosphate in a Mouse Model of Traumatic Brain Injury

Traumatic brain injury (TBI) is traditionally characterized by primary and secondary injury phases, both contributing to pathological and morphological changes. The mechanisms of damage and chronic consequences of TBI remain to be fully elucidated, but synaptic homeostasis disturbances and impaired energy metabolism are proposed to be a major contributor. It has been proposed that an increase of extracellular (eATP) adenosine triphosphate (ATP) in the area immediately surrounding impact may play a pivotal role in this sequence of events. After tissue injury, rupture of cell membranes allows release of intracellular ATP into the extracellular space, triggering a cascade of toxic events and inflammation. ATP is a ubiquitous messenger; however, simple and reliable techniques to measure its concentration have proven elusive. Here, we integrate a sensitive bioluminescent eATP sensor known as pmeLUC, with a controlled cortical impact mouse model to monitor eATP changes in a living animal after injury. Using the pmeLUC probe, a rapid increase of eATP is observed proximal to the point of impact within minutes of the injury. This event is significantly attenuated when animals are pretreated with an ATP hydrolyzing agent (apyrase) before surgery, confirming the contribution of eATP. This new eATP reporter could be useful for understanding the role of eATP in the pathogenesis in TBI and may identify a window of opportunity for therapeutic intervention.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:38

Enthalten in:

Journal of neurotrauma - 38(2021), 5 vom: 16. März, Seite 655-664

Sprache:

Englisch

Beteiligte Personen:

Faroqi, Ayman H [VerfasserIn]
Lim, Melina J [VerfasserIn]
Kee, Emma C [VerfasserIn]
Lee, Jannifer H [VerfasserIn]
Burgess, Jeremy D [VerfasserIn]
Chen, Ridong [VerfasserIn]
Di Virgilio, Francesco [VerfasserIn]
Delenclos, Marion [VerfasserIn]
McLean, Pamela J [VerfasserIn]

Links:

Volltext

Themen:

8L70Q75FXE
Adenosine Triphosphate
Apyrase
CCI
EC 3.6.1.5
Extracellular ATP
In vivo Imaging
Journal Article
PmeLUC
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
TBI

Anmerkungen:

Date Completed 07.01.2022

Date Revised 07.01.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1089/neu.2020.7226

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM315075007