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Leithner C, Royl G, Offenhauser N, et al. Pharmacological uncoupling of activation induced increases in CBF and CMRO2. J Cereb Blood Flow Metab. 2009;30(2):311-22doi: 10.1038/jcbfm.2009.211.
Leithner, C., Royl, G., Offenhauser, N., Füchtemeier, M., Kohl-Bareis, M., Villringer, A., Dirnagl, U., & Lindauer, U. (2010). Pharmacological uncoupling of activation induced increases in CBF and CMRO2. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 30(2), 311-22. https://doi.org/10.1038/jcbfm.2009.211
Leithner, Christoph, et al. "Pharmacological uncoupling of activation induced increases in CBF and CMRO2." Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism vol. 30,2 (2010): 311-22. doi: https://doi.org/10.1038/jcbfm.2009.211
Leithner C, Royl G, Offenhauser N, Füchtemeier M, Kohl-Bareis M, Villringer A, Dirnagl U, Lindauer U. Pharmacological uncoupling of activation induced increases in CBF and CMRO2. J Cereb Blood Flow Metab. 2010 Feb;30(2):311-22. doi: 10.1038/jcbfm.2009.211. Epub 2009 Sep 30. PMID: 19794398; PMCID: PMC2949119.
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J Cereb Blood Flow Metab. 2010 Feb;30(2):311-22. doi: 10.1038/jcbfm.2009.211. Epub 2009 Sep 30.

Pharmacological uncoupling of activation induced increases in CBF and CMRO2.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Christoph Leithner, Georg Royl, Nikolas Offenhauser, Martina Füchtemeier, Matthias Kohl-Bareis, Arno Villringer, Ulrich Dirnagl, Ute Lindauer

Affiliations

  1. Department of Experimental Neurology, Charité Universitätsmedizin, Center for Stroke Research Berlin, Berlin, Germany.

PMID: 19794398 PMCID: PMC2949119 DOI: 10.1038/jcbfm.2009.211

Abstract

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.

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