Cortical spreading depression associated hyperperfusion: biochemical and molecular mechanisms and definition of vascular 'fingerprints'

Uwe Reuter, Tilo Wolf, Jens Dreier,Guy Arnold, Lorenz Gold, Ulrich Dirnagl

 

Cortical spreading depression is supposed to be the pathophysiological correlate of the migraine aura. CSD is accompanied by a short hyperperfusion which is followed by a long lasting hypoperfusion. These blood flow changes are also reflected in profound changes in hemoglobin oxygenation. Because periinfarct depolarizations (PID), a CSD like phenomenon in focal cerebral ischemia lacking this hyperperfusion, contribute to brain tissue damage, we are investigating the biochemical and molecular mechanisms and functional role of CSD associated hyperperfusion. Particular focus is placed on neurotransmitters of the trigeminal and parasympathetic nerve systems (CGRP, substance P, ACH), vasoactive ions/molecules (K+, NO etc.), second messenger systems (cGMP, cAMP), as well as on ion channels and pumps (e.g. Na/K ATPase). It is the ultimate goal of this project to - elucidate mechanisms that couple this intense metabolic activation of neurons and glia to cerebral blood flow, - to provide basic knowledge and characteristic vascular 'fingerprints' to detect this phenomenon in human migraineurs and stroke patients using functional neuroimaging, and to - clarify mechanisms if and how CSD like phenomena (PID) cause damage in stroke.

Methods

Cranial windows, Laser Doppler flowmetry, electrophysiology, near infrared spectroscopy

Grants

DFG SFB-507 A1, DFG Ei 207/2-1, DFG Di 454/8-1

Selected publications
  1. Reuter, U., Weber, J.R., Gold, L.., Arnold, G., Wolf, T., Dreier, J., Lindauer, U., Dirnagl, U. Cortical spreading depression associted hyperemia in rats: role of the trigeminal and parasympathetic systems. submitted
  2. 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
  3. 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
  4. Villringer, A. and Dirnagl, U. Coupling of brain activity and cerebral blood flow - basis of functional neuroimaging. Cerebrovasc Brain Metab Rev (1995) 7:240-276
  5. Wolf, T., Lindauer, U., Villringer, A., and Dirnagl, U. Excessive oxygen or glucose supply do not alter the blood flow response to somatosensory stimulation or spreading depression in rats. submitted