Systemic theophylline augments the blood oxygen level-dependent response to forepaw stimulation in rats.
OBJECTIVE
Functional MR imaging with blood oxygen level-dependent (BOLD) contrast enhancement is believed to rely on changes in cerebral blood flow and deoxyhemoglobin level to estimate the location and degree of neural activation. We studied the relationship between neural activation and the observed BOLD response by using theophylline, an antagonist of the inhibitory neurotransmitter adenosine and a potent inhibitor of the vasodilatory response to neural activation.


METHODS
Using a rat model with electrical forepaw stimulation, we performed fMRI measurements before and after the systemic injection of either theophylline (0.1 mmol/kg) or an equivalent volume of saline. Changes in the BOLD response were quantified by determining the number of activated voxels and the amplitude of the BOLD response for each animal in the theophylline and saline groups.


RESULTS
The theophylline group had a significantly Tincreased BOLD response (70-150% increased activated voxel count and 60-65% increased BOLD response amplitude) at 45 and 60 minutes after systemic injection compared with baseline. The response of the saline-injected control group did not change significantly.


CONCLUSIONS
The administration of systemic theophylline significantly augmented the BOLD response due to either an elevation of resting deoxyhemoglobin levels or the neuroexcitatory effect of theophylline. This effect potentially could be used in human fMRI studies to increase the sensitivity of the BOLD response.
Morton
Douglas W
DW
Department of Radiology, University of Washington, Seattle 98195, USA.
Maravilla
Kenneth R
KR
Meno
Joseph R
JR
Winn
H Richard
HR
D000241:Adenosine / Q000037:antagonists & inhibitors; D000818:Animals; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004558:Electric Stimulation; D005552:Forelimb / Q000294:innervation; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010100:Oxygen / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D013806:Theophylline; D000241:Adenosine; D010100:Oxygen