Cerebral Oxygenation in Awake Rats during Acclimation and Deacclimation to Hypoxia: AnIn VivoElectron Paramagnetic Resonance Study

Abstract

Cerebral oxygenation in awake rats during acclimation and deacclimation to hypoxia: an in vivo EPR study. High Alt. Med. Biol. 12:71-77, 2011.-Exposure to high altitude or hypobaric hypoxia results in a series of metabolic, physiologic, and genetic changes that serve to acclimate the brain to hypoxia. Tissue Po 2 (Pto 2 ) is a sensitive index of the balance between oxygen delivery and utilization and can be considered to represent the summation of such factors as cerebral blood flow, capillary density, hematocrit, arterial Po 2 , and metabolic rate. As such, it can be used as a marker of the extent of acclimation. We developed a method using electron paramagnetic resonance (EPR) to measure Pto 2 in unanesthetized subjects with a chronically implanted sensor. EPR was used to measure rat cortical tissue Pto 2 in awake rats during acute hypoxia and over a time course of acclimation and deacclimation to hypobaric hypoxia. This was done to simulate the effects on brain Pto 2 of traveling to altitude for a limited period. Acute reduction of inspired O 2 to 10% caused a decline from 26.7 AE 2.2 to 13.0 AE 1.5 mmHg (mean AE SD). Addition of 10% CO 2 to animals breathing 10% O 2 returned Pto 2 to values measured while breathing 21% O 2, indicating that hypercapnia can reverse the effects of acute hypoxia. Pto 2 in animals acclimated to 10% O 2 was similar to that measured preacclimation when breathing 21% O 2 . Using a novel, individualized statistical model, it was shown that the T 1/2 of the Pto 2 response during exposure to chronic hypoxia was approximately 2 days. This indicates a capacity for rapid adaptation to hypoxia. When subjects were returned to normoxia, there was a transient hyperoxygenation, followed by a return to lower values with a T 1/2 of deacclimation of 1.5 to 3 days. These data indicate that exposure to hypoxia results in significant improvements in steady-state oxygenation for a given inspired O 2 and that both acclimation and deacclimation can occur within days.

Combined in Vivo Amperometric Oximetry and Electrophysiology in a Single Sensor: A Tool for Epilepsy Research

“…Although the relative values are clear in the present work, the low number of animals used (in particular for determination in the striatum and CA1 region of the hippocampus) does not allow broad generalization of the observed differences. The values reported here are in good agreement with those reported in the literature for the cerebral cortex, as shown in Table , for both anesthetized and awake rats, determined using different techniques, namely, electron paramagnetic resonance (EPR) oximetry, , Clark-type microelectrodes, and fluorescent quenching fiber optrode . Interestingly, values reported for the hippocampus in freely moving rats show great variation , and are higher than those found by us, likely reflecting to different electrode positioning within the brain.…”

Training the Brain to Survive Stroke

“…Hypoxic/ischemic preconditioning studies are largely of short duration (up to a few hours). However hypoxia acclimation is known to require days to weeks [4] , [19] , [20] . Inducible factors such as HIF and VEGF have returned to baseline by three weeks post stimulation [21] and so mechanisms which require direct action of these cytokines may no longer be functioning.…”

Hypoxia-inducible factors regulate human and rat cystathionine β-synthase gene expression

“…Chronic exposure to high altitude is associated with increased cerebral blood flow, which has been attributed to hypoxia-induced vasodilation leading to increased oxygenation [29-31]. Our results suggest that HIF-dependent CBS expression may contribute to this adaptive response.…”

“…Measurement of tissue partial pressure of O 2 ( P T O 2 ) in the rat cerebral cortex has yielded mean values from 14 to 27 mm Hg with considerable spatial and temporal variation [2-4]. When the ambient O 2 concentration was reduced from 21% to 10%, the mean cerebral P T O 2 decreased to a mean of 7 to 13 mm Hg [5]. A homeostatic balance between O 2 supply and demand is maintained by autoregulation of the cerebral microcirculation, in which reduced local O 2 availability triggers vasodilation, thereby increasing local blood flow and O 2 delivery.…”