Striatal and Cortical BOLD, Blood Flow, Blood Volume, Oxygen Consumption, and Glucose Consumption Changes in Noxious Forepaw Electrical Stimulation

Abstract

Recent reports showed noxious forepaw stimulation in rats evoked an unexpected sustained decrease in cerebral blood volume (CBV) in the bilateral striatum, whereas increases in spike activity and Fos-immunoreactive cells were observed. This study aimed to further evaluate the hemodynamic and metabolic needs in this model and the sources of negative functional magnetic resonance imaging (fMRI) signals by measuring blood oxygenation-level-dependent (BOLD), cerebral-blood-flow (CBF), CBV, and oxygen-consumption (i.e., cerebral metabolic rate of oxygen (CMRO 2 )) changes using an 11.7-T MRI scanner, and glucose-consumption (i.e., cerebral metabolic rate of glucose (CMRglc)) changes using micro-positron emission tomography. In the contralateral somatosensory cortex, BOLD, CBF, CBV, CMRO 2 (n = 7, P < 0.05), and CMRglc (n = 5, P < 0.05) increased. In contrast, in the bilateral striatum, BOLD, CBF, and CBV decreased (P < 0.05), CMRO 2 decreased slightly, although not significantly from baseline, and CMRglc was not statistically significant from baseline (P > 0.05). These multimodal functional imaging findings corroborate the unexpected negative hemodynamic changes in the striatum during noxious forepaw stimulation, and support the hypothesis that striatal hemodynamic response is dominated by neurotransmittermediated vasoconstriction, overriding the stimulus-evoked fMRI signal increases commonly accompany elevated neuronal activity. Multimodal functional imaging approach offers a means to probe the unique attributes of the striatum, providing novel insights into the neurovascular coupling in the striatum. These findings may have strong implications in fMRI studies of pain.

BOLD Imaging in Awake Wild-Type and Mu-Opioid Receptor Knock-Out Mice Reveals On-Target Activation Maps in Response to Oxycodone

“…In a series of studies, Shih and collaborators characterized a counter-intuitive negative BOLD signal change in the striatum of the rat in the face of increased neuronal activity caused by pain and exacerbated by morphine treatment during a noxious stimulus (Shih et al, 2009, 2011, 2012). The effect of morphine was blocked with naloxone pretreatment, evidence of opioid receptor involvement.…”

Imaging Neurovascular Function and Functional Recovery after Stroke in the Rat Striatum Using Forepaw Stimulation

“…1 It plays a pivotal role in several neurodegenerative disorders and regulating motor behavior. Recent reports showed that unilateral noxious forepaw electrical stimulation in rats evoked sustained negative blood oxygenation level dependent (BOLD), cerebral blood flow (CBF), and cerebral blood volume (CBV) functional magnetic resonance imaging (fMRI) responses in the bilateral striatum with no significant difference between two hemispheres, [2][3][4][5][6] while the neuronal spike and c-Fos activities increased. 6 This negative response has also been observed in epileptic rats during whisker stimulation 7 or normal rats during direct nerve stimulation.…”

“…Contralateral CPu (cCPu) response was not recorded because of our hardware limitation and the fact that no difference was detected between the two hemispheres in this model. [2][3][4][5][6] To investigate whether the striatal negative fMRI response can serve as a marker for striatal functional integrity, we used stimulation of 10 mA, 3 milliseconds pulse width, and 12 Hz in two groups of rats underwent 20-and 45-minute middle cerebral artery occlusion (MCAO) and followed the fMRI responses up to 28 days.…”

Micro-Positron Emission Tomography Imaging of Rat Brain Metabolism during Expression of Contextual Conditioning

“…This is a relatively small group size, but not uncommon for small-animal PET imaging studies (Barbarich-Marsteller et al, 2005;Higuera-Matas et al, 2008;Soto-Montenegro et al, 2009;Shih et al, 2011).…”