Cerebral blood flow and BOLD fMRI responses to hypoxia in awake and anesthetized rats

Abstract

This study investigated the functional MRI responses to graded hypoxia in awake/restrained and anesthetized animals by measuring cerebral blood flow (CBF) and blood oxygenation (BOLD) changes and estimating changes in cerebral metabolic rate of oxygen (CMRO 2 ). Hypoxia in isoflurane anesthetized rats reduced blood pressure but did not change heart rate and respiration rate. In contrast, hypoxia in awake animals showed compensatory responses by sustaining blood pressure, increasing heart rate and respiration rate. Basal CBF was higher under isoflurane anesthesia than awake state because isoflurane is a vasodilator. Graded hypoxia decreased BOLD signals. Surprisingly, hypoxia also decreased CBF likely because hypoxia induced hypocapnia. Hypoxiainduced CBF and BOLD decreases were smaller in awake, relative to anesthetized, rats at low pO 2 , but similar at high pO 2 . CBF leveled off with decreasing hypoxia-induced pCO 2 in awake rats, but monotonically decreased in anesthetized rats. CMRO 2 estimated using a biophysical BOLD model did not change under mild hypoxia but was reduced under severe hypoxia relative to baseline. These results showed that isoflurane attenuated automomic responses to hypoxia, hypoxia-induced hypocapnia dominated CBF changes, tissues in awake conditions appeared better oxygenated, and severe hypoxia reduced oxygen metabolism. This study underscored the marked differences in BOLD and CBF MRI responses to hypoxia in vivo between awake and anesthetized conditions and has implications for functional MRI studies of hypoxia in anesthetized animal models.

Water diffusion in brain cortex closely tracks underlying neuronal activity

“…The effects of isoflurane on neural tissue and hemodynamics are complex. Isoflurane is an anesthetic agent known to disrupt neurovascular coupling (22,26), depending on dosage, as well as to suppress the neural activity in cerebral cortices (23)(24)(25). Because isoflurane is not only a vasodilator, but also a modulator of neurovascular coupling, it can disturb the behavior of the hemodynamic response nonlinearly (31).…”

“…Isoflurane is an anesthetic agent known to disrupt neurovascular coupling (22), depending on dosage, as well to suppress the neural activity in cerebral cortices (23)(24)(25).…”

Functional MRI and functional connectivity of the visual system of awake pigeons

“…A large number of studies in various mammalian species reveal differences in the result patterns of (rs)fMRI studies under awake and anaesthetized conditions [4,7,11,12]. Since different bird species represent interesting models for the analyses of neural plasticity, song production, learning, and cognition, it is necessary to develop and test a procedure for awake bird MRI.…”

“…rats [7][8][9] and mice [10]. Moreover since it is shown that both in human [11] and nonhuman primates [12] brain state during rest is not fully comparable with the anesthetized state, new studies increasingly start to study rsfMRI in awake rodents [13][14][15][16][17].…”

Metabotropic glutamate receptor modulation, translational methods, and biomarkers: relationships with anxiety

“…There have, however, been a number of efforts to image the brain in awake rodents, with both fMRI and (micro)PET (Hosoi et al 2005;Lahti et al 1998;Momosaki et al 2004), and in alert monkeys with fMRI (Logothetis et al 1999). Thus far, only passive reactivity to, for instance, whisker or forepaw stimulation (Peeters et al 2001), hypoxia (Duong 2007), or pharmacological stimuli Skoubis et al 2006) has been measured in rodents. The ability to image awake animals raises the possibility of testing reactivity to stimuli under the influence of a test compound and to relate brain activity to behavior.…”