Effects of hypoxia, hyperoxia, and hypercapnia on baseline and stimulus-evoked BOLD, CBF, and CMRO2 in spontaneously breathing animals

Abstract

Functional magnetic resonance imaging (fMRI) was used to investigate the effects of inspired hypoxic, hyperoxic, and hypercapnic gases on baseline and stimulus-evoked changes in blood oxygenation level-dependent (BOLD) signals, cerebral blood flow (CBF), and the cerebral metabolic rate of oxygen (CMRO 2 ) in spontaneously breathing rats under isoflurane anesthesia. Each animal was subjected to a baseline period of six inspired gas conditions (9% O 2 , 12% O 2 , 21% O 2 , 100% O 2 , 5% CO 2 , and 10% CO 2 ) followed by a superimposed period of forepaw stimulation. Significant stimulus-evoked fMRI responses were found in the primary somatosensory cortices. Relative fMRI responses to forepaw stimulation varied across gas conditions and were dependent on baseline physiology, whereas absolute fMRI responses were similar across moderate gas conditions (12% O 2 , 21% O 2 100% O 2 , and 5% CO 2 ) and were relatively independent of baseline physiology. Consistent with data obtained using well-established techniques, baseline and stimulus-evoked CMRO 2 were invariant across moderate physiological perturbations thereby supporting a CMRO 2 -fMRI technique for non-invasive CMRO 2 measurement. However, under 9% O 2 and 10% CO 2 , stimulus-evoked CBF and BOLD were substantially reduced and the CMRO 2 formalism appeared invalid, likely due to attenuated neurovascular coupling and/or a failure of the model under extreme physiological perturbations. These findings demonstrate that absolute fMRI measurements help distinguish neural from non-neural contributions to the fMRI signals and may lend a more accurate measure of brain activity during states of altered basal physiology. Moreover, since numerous pharmacologic agents, pathophysiological states, and psychiatric conditions alter baseline physiology independent of neural activity, these results have implications for neuroimaging studies using relative fMRI changes to map brain activity.

Normobaric Hyperoxia Delays Perfusion/Diffusion Mismatch Evolution, Reduces Infarct Volume, and Differentially Affects Neuronal Cell Death Pathways after Suture Middle Cerebral Artery Occlusion in Rats

“…Blood gases, electrolytes, and pH did not differ between time points and groups. In accordance with previously reported data, 100% NBO increased PaCO 2 and PaO 2 levels compared with baseline values as well as compared with controls (Table 1), the former presumably via induction of mild hypoventilation (Sicard and Duong, 2005). Interestingly, mean arterial blood pressure of NBO-treated animals was significantly elevated at 120 and 180 mins compared with controls.…”

Blood-flow magnetic resonance imaging of the retina

“…The difference between spontaneous breathing in previous study of the rat brains and mechanical ventilation in this study could not explain the difference in response magnitude because animals under spontaneous breathing increase respiration rate which should slightly reduce blood CO 2 (Sicard and Duong, 2005). Similar hypercapnia-induced changes in cerebral blood flow in awake humans and animals under different anesthetics have also been reported in the literatures, although quantitative comparison is less informative due to differences in experimental conditions.…”

“…Basal blood flow of the retina, including the choroid, under 1% isoflurane (6.3±1.0 ml/g/min) is markedly higher than cerebral blood flow, which have been reported to be 0.9±0.13 ml/g/ min (Liu et al, 2004) and 1.1±0.04 ml/g/min (Sicard and Duong, 2005) under essentially identical experimental conditions. The blood-flow values reported at current spatial resolution are a weighted average of the retinal and choroidal blood flow.…”

“…In the rat brain, hypercapnic (5% CO2 in air) inhalation increased cerebral blood flow by 25% (Sicard et al, 2003b) and 52% (Sicard and Duong, 2005) in rats under essentially identical experimental conditions (except the animals breathed spontaneously). The difference between spontaneous breathing in previous study of the rat brains and mechanical ventilation in this study could not explain the difference in response magnitude because animals under spontaneous breathing increase respiration rate which should slightly reduce blood CO 2 (Sicard and Duong, 2005).…”

“…In short, hypercapnia-induced blood-flow increase appears to be smaller in the retina than in the brain. This may be due to the high basal choroidal blood flow, which could reduce head room for additional vasodilation (Sicard and Duong, 2005). The use of isoflurane could further accentuate this effect.…”