Abstract
In this work a method for measuring brain oxygen partial pressure with confocal phosphorescence lifetime microscopy system is reported. When used in conjunction with a dendritic phosphorescent probe, Oxyphor G4, this system enabled minimally invasive measurements of oxygen partial pressure (pO2) in cerebral tissue with high spatial and temporal resolution during 4-AP induced epileptic seizures. Investigating epileptic events, we characterized the spatio-temporal distribution of the "initial dip" in pO2 near the probe injection site and along nearby arterioles. Our results reveal a correlation between the percent change in the pO2 signal during the "initial dip" and the duration of seizure-like activity, which can help localize the epileptic focus and predict the length of seizure.
Highlights
The nature of coupling between neuronal activity and the associated metabolic response is a subject of great debate [1,2,3]
In our present work, which focused on tissue oxygen changes at multiple locations (>2) during acute epileptiform events, we show a significant initial dip at multiple locations in our mice
Our results further suggest that the increased cerebral blood flow (CBF) and cerebral blood volume (CBV) will supply more oxygen to the tissue near an artery, but may not meet the demands of oxygen metabolism far away from an artery
Summary
The nature of coupling between neuronal activity and the associated metabolic response is a subject of great debate [1,2,3]. Evaluating tissue oxygen changes and quantifying oxidative metabolism is crucial for the understanding of neuropathologies in the brain, such as Parkinson’s disease, stroke, epilepsy, Alzheimer’s disease [4,5,6,7] and developing effective therapies. While blood oxymetry provides a proxy for tissue oxygenation, under conditions of large metabolic demand and/or non-linear hemodynamic response [8], such as in epilepsy, measuring blood oxygenation alone is not sufficient. In order to investigate such conditions, monitoring of the spatio-temporal characteristics of oxygen changes in cerebral tissue is crucial. Several techniques have been developed to measure cerebral oxygenation in vivo, including positron emission tomography (PET), near-infrared spectroscopy (NIRS), blood-oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) and oxygen polarimetric electrodes [9,10,11,12]. PLOS ONE | DOI:10.1371/journal.pone.0135536 August 25, 2015
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