Journal of neuroscience methods

G Model NSM-5737; No. of Pages 9

ARTICLE IN PRESS
Journal of Neuroscience Methods xxx (2010) xxx–xxx

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Journal of Neuroscience Methods
journal homepage: www.elsevier.com/locate/jneumeth

A method for measuring brain partial pressure of oxygen in unanesthetized unrestrained subjects: The effect of acute and chronic hypoxia on brain tissue PO2E. Ortiz-Prado a,b , Siraj Natah a,b , Sathyanarayanan Srinivasan a,b , Jeff F. Dunn a,b,c,∗
a b c

Department of Radiology, Faculty of Medicine, University of Calgary, Canada Hotchkiss Brain Institute, Canada Experimental Imaging Centre, Canada

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a b s t r a c t
The level of tissue oxygenation provides information related to the balance between oxygen delivery,oxygen utilization, tissue reactivity and morphology during physiological conditions. Tissue partial pressure of oxygen (PtO2 ) is influenced by the use of anesthesia or restraint. These factors may impact the absolute level of PtO2 . In this study we present a novel fiber optic method to measure brain PtO2 . This method can be used in unanesthetized, unrestrained animals, provides absolute values forPO2 , has a stable calibration, does not consume oxygen and is MRI compatible. Brain PtO2 was studied during acute hypoxia, as well as before and after 28 days of high altitude acclimatization. A sensor was chronically implanted in the frontal cortex of eight Wistar rats. It is comprised of a fiber optic probe with a tip containing material that fluoresces with an oxygen dependent lifetime. BrainPtO2 declines by 80% and 76% pre- and post-acclimatization, respectively, when the fraction of inspired oxygen declines from 0.21 to 0.08. In addition, a linear relationship between brain PtO2 and inspired O2 levels was demonstrated r2 = 0.98 and r2 = 0.99 (pre- and post-acclimatization). Hypoxia acclimatization resulted in an increase in the overall brain PtO2 by approximately 35%. This paperdemonstrates the use of a novel chronically implanted fiber optic based sensor for measuring absolute PtO2 . It shows a very strong linear relationship in awake animals between inspired O2 and tissue O2 , and shows that there is a proportional increase in PtO2 over a range of inspired values after exposure to chronic hypoxia. © 2010 Elsevier B.V. All rights reserved.

Article history: Received 22 July2009 Received in revised form 19 August 2010 Accepted 23 August 2010 Keywords: Brain High altitude Oxygen Partial pressure of oxygen Hypoxia Unrestrained Anesthesia

1. Introduction Tissue PO2 (PtO2 ) provides information on tissue oxygenation, which is determined by the balance between oxygen delivery and utilization. The PtO2 reports values in the interstitial fluid along the diffusiongradient between the capillaries (oxygen supply) and the site of oxygen utilization (the mitochondria). An adequate supply of oxygen is critical for the cell survival in the brain. The measurement of brain PtO2 provides a quantifiable measure of oxygenation which has been related to cellular viability in the brain (Dings et al., 1996, 1998) providing important information related to the outcome andprognosis, and monitoring of PtO2 could provide useful information on the health status of the brain (Dings et al., 1998; Stiefel et al., 2005, 2006). PtO2 has been used to provide insight into the effect on oxygenation of alterations in such variables as hemoglobin p50, hematocrit, angiogenesis, vascu-

∗ Corresponding author at: Department of Radiology, Faculty of Medicine, University of Calgary,3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada. Tel.: +1 403 210 3886; fax: +1 403 221 3230. E-mail address: dunnj@ucalgary.ca (J.F. Dunn). 0165-0270/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jneumeth.2010.08.019

lar density, alterations in metabolic rate and adaptation to hypoxia (Dunn et al., 2000; Plock et al., 2005; Rascon and Harrison, 2005;...