Pharmacological uncoupling of activation induced increases in CBF and CMRO2.
Neurovascular coupling provides the basis for many functional neuroimaging techniques. Nitric oxide (NO), adenosine, cyclooxygenase, CYP450 epoxygenase, and potassium are involved in dilating arterioles during neuronal activation. We combined inhibition of NO synthase, cyclooxygenase, adenosine receptors, CYP450 epoxygenase, and inward rectifier potassium (Kir) channels to test whether these pathways could explain the blood flow response to neuronal activation. Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) of the somatosensory cortex were measured during forepaw stimulation in 24 rats using a laser Doppler/spectroscopy probe through a cranial window. Combined inhibition reduced CBF responses by two-thirds, somatosensory evoked potentials and activation-induced CMRO(2) increases remained unchanged, and deoxy-hemoglobin (deoxy-Hb) response was abrogated. This shows that in the rat somatosensory cortex, one-third of the physiological blood flow increase is sufficient to prevent microcirculatory increase of deoxy-Hb concentration during neuronal activity. The large physiological CBF response is not necessary to support small changes in CMRO(2). We speculate that the CBF response safeguards substrate delivery during functional activation with a considerable 'safety factor'. Reduction of the CBF response in pathological states may abolish the BOLD-fMRI signal, without affecting underlying neuronal activity.
Department of Experimental Neurology, Charité Universitätsmedizin, Center for Stroke Research Berlin, Berlin, Germany.
Christoph
C
Leithner
Georg
G
Royl
Nikolas
N
Offenhauser
Martina
M
Füchtemeier
Matthias
M
Kohl-Bareis
Arno
A
Villringer
Ulrich
U
Dirnagl
Ute
U
Lindauer
D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects / Q000502:physiology; D008297:Male; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013003:Somatosensory Cortex / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*
D004791:Enzyme Inhibitors; D024661:Potassium Channels, Inwardly Rectifying