Coupling of cerebral blood flow and metabolism: molecular, biochemical, and hemodynamic mechanisms

Ute Lindauer, Tilo Wolf, Jens Dreier, Dirk Megow, Ulrich Dirnagl

Cerebral blood flow is tightly coupled to synaptic activity (neurovascular coupling). Most modern functional neuroimaging methods (fMRI, PET, near infrared spectroscopy) use neurovascular coupling to map brain activity. It is the aim of this project to investigate the molecular and biochemical mechanisms that lead from neuronal activity to smooth muscle relaxation, and pharmacological as well as pathophysiological interference with these mechanisms. Particular attention is paid to the messenger/meditator nitric oxide, as well as to potassium and adenosine. On the cerebral smooth muscle the focus is on various potassium channels and the guanylate/adenylate cyclase system. Our studies use the physiological activation responses in the Whisker system of the rat, with biochemical and optical access to the somatosensory cortex via a closed cranial window. In addition, isolated artery preparations and cultivated primary cerebral endothelial cells and neurons are studied. The ultimate goal of these studies is to provide the physiological basis for functional neuroimaging in health and disease.

Methods

Cranial windows, Whisker barrel cortex, cell culture, isolated cerebral arteries, confocal laser scanning microscopy, NO-chemiluminescence, Laser Doppler flowmetry, near infrared spectroscopy, evoked potentials

Grants

DFG Di 454-4/3, Di DFG 454-8/1, DFG Ei 207-2/1, Human Frontier Science Project Organization

Selected references
  1. Lindauer, U., Megow, D., Schultze, J., Weber, J.R., and Dirnagl, U. Nitric oxide synthase inhibition does not affect somatosensory evoked potentials in the rat. Neurosci.Lett. 216:1-4, 1996.
  2. Weikert, S., Freyer, D., Weih, M., Isaev, N., Busch, C., Schultze, J., Megow, D., and Dirnagl, U. Rapid, Ca2+-dependent NO-production from CNS-cells in culture measured by NO-nitrite/ozone chemoluminescence. Brain Res. 1996.(In Press)
  3. Lindauer, U., Dreier, J., Angstwurm, K., Villringer, A., Einhäupl, K. M., and Dirnagl, U. Role of nitric oxide synthase inhibition in leukocyte- endothelium interaction in the rat pial microvasculature. J Cereb Blood Flow Metab 16 (1996):1143-1153.
  4. Wolf, T., Obrig, H., Dreier, J., Back, T., Villringer, A., and Dirnagl, U. Systemic nitric oxide synthase (NOS) inhibition does not affect brain oxygenation during cortical spreading depression (CSD) in rats: A non-invasive near infrared spectroscopy (NIRS) and laser Doppler flowmetry (LDF) study. J Cereb Blood Flow Metab 16 (1996):1100-1107
  5. Dreier J., Körner,K., Görner, A., Weih,M., Villringer,A. Dirnagl, U. Nitric oxide modulates the CBF response to increased extracellular potassium J Cereb Blood Flow Metab 15:914-191, 1995
  6. Dirnagl U, Niwa K, Lindauer U, Villringer A (1994) Coupling of cerebral blood flow to neuronal activation: Role of adenosine and nitric oxide. Am J Physiol 267:H296-H301.