Zusammenfassung
Zwischen der jeweilig lokalen Hirnaktivität und der regionalen Hirndurchblutung besteht
eine enge Korrelation, die mit dem Begriff der neurovaskulären Kopplung beschrieben
wird. In der folgenden Übersicht wollen wir ein kombiniertes EEG und transkranielles
Dopplerverfahren vorstellen, mit dem die neurovaskuläre Kopplung unter klinischen
Bedingungen einfach und zuverlässig am Menschen bestimmt werden kann. Im Falle der
Differenzierung zwischen einer Alzheimer und vaskulären Demenz wollen wir die Vorzüge
der neuen Methode darlegen.
Abstract
There is a tight coupling between neuronal activity and regional cerebral blood flow,
which is called neurovascular coupling. In the following overview we will describe
a combined EEG and transcranial Doppler approach that allows investigation of the
neurovascular coupling in humans in an easy and accurate manner. In the case of the
differentiation between Alzheimer's disease and a vascular type of dementia we wish
to show the advantages of the new method.
Schlüsselwörter
Funktionelle transkrankielle Dopplersonographie - Visuell evozierte Potentiale - neurovaskuläre
Kopplung - Hirndurchblutung - funktionelle Aktivierung
Key words
Functional transcranial Doppler - visual evoked potential - neurovascular coupling
- cerebral blood flow - functional activation
Literatur
- 1
Kuschinsky W.
Coupling of function, metabolism, and blood flow in the brain.
Neurosurg Rev.
1991;
14
163-168
- 2
Dirnagl U, Niwa K, Lindauer U, Villringer.
Coupling of cerebral blood flow to neuronal activation: role of adenosine and nitric
oxide.
Am J Physiol.
1994;
267
H296-H301
- 3
Villringer A, Dirnagl U.
Coupling of brain activity and blood flow: Basis of functional neuroimaging.
Cerebrovasc Brain Metab Rev.
1995;
7
240-276
- 4
Akima M, Nonaka H, Kagesawa M, Tanaka K.
A study on the microvasculature of the cerebral cortex. Fundamental architecture and
its senile change in the frontal cortex.
Lab Invest.
1986;
55
482-489
- 5
Anderson CM, Nedergaard M.
Astrocyte-mediated control of cerebral microcirculation.
TINS.
2003;
26
340-344
- 6
Nehls V, Denzer K, Drenckhahn D.
Pericyte involvement in capillary sprouting during angiogenesis in situ.
Cell Tissue Res.
1992;
270
469-474
- 7
Branston NM.
Neurogenic control of the cerebral circulation.
Cerebrovascular and Brain Met Rev.
1995;
7
338-349
- 8
Sercombe R, Aubineau P, Edvinsson L, Mamo H, Owman C, Pinard E, Seylaz J.
Neurogenic influence on local cerebral blood flow.
Neurology.
1975;
25
954-963
- 9
Lindauer U, Kunz A, Schuh-Hofer S, Vogt J, Dreier JP, Dirnagl U.
Nitric oxide from perivascular nerves modulates cerebral arterial pH reactivity.
Am J Physiol.
2001;
281
H1353-H1363
- 10
Iadecola C.
Neurovascular regulation in the normal brain and in Alzheimer's disease.
Nature Rev Neurosci.
2004;
5
347-360
- 11
Hartlage-Rubsamen M, Schliebs R.
Rat basal forebrain cholinergic lesion affects neuronal nitric oxide synthase activity
in hippocampal and neocortical target regions.
Brain Res.
2001;
889
155-164
- 12
Tong XK, Hamel E.
Regional cholinergic denervation of cortical microvessels and nitric oxide synthase-containing
neurons in Alzheimer disease.
Neuroscience.
1999;
92
163-175
- 13
Cholet N, Bonvento G, Seylaz J.
Effect of neuronal NO synthase inhibition on the cerebral vasodilatory response to
somatosensory stimulation.
Brain Res.
1996;
708
197-200
- 14
Betz E, Csornai M.
Action and interaction of perivascular H+, K+ and Ca++ on pial arteries.
Pflügers Arch.
1978;
374
67-72
- 15
Ko KR, Ngai AC, Winn HR.
Role of adenosine in regulation of regional cerebral blood flow in sensory cortex.
Am J Physiol.
1990;
259
H1703-H1708
- 16
Harder DR, Zhang C, Gebremedhin D.
Astrocytes function in matching blood flow to metabolic activity.
News Physiol Sci.
2002;
16
27-31
- 17
Zonta M, Angulo MC, Gobbo S, Rosengarten B, Hossmann KA, Pozzan T, Carmignoto G.
Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation.
Nature Neurosci.
2003;
6
43-50
- 18
Arthurs OJ, Boniface S.
How well do we understand the neural origins of the fMRI BOLD signal?.
TINS.
2002;
25
27-31
- 19
Buxton RN, Frank LR.
A model for the coupling between cerebral blood flow and oxygen metabolism during
neural stimulation.
J Cereb Blood Flow Metab.
1997;
17
64-72
- 20
Heiss WD.
Flow thresholds of functional and morphological damage of brain tissue.
Stroke.
1983;
14
329-331
- 21
Hossmann K-A.
Viability thresholds and the penumbra of focal ischemia.
Ann Neurol.
1994;
36
557-565
- 22
Mies G, Kohno K, Hossmann K-A.
MK-801, a glutamate antagonist, lowers flow threshold for inhibition of protein synthesis
after middle cerebral artery occlusion in rats.
Neurosci Lett.
1993;
155
65-68
- 23
Schellinger PD, Kaste M, Hacke W.
An update on thrombolytic therapy for acute stroke.
Curr Opin Neurol.
2004;
17
69-77
- 24
Bandettini PA, Wong CE, Hinks RS, Tikofsky RS, Hyde JS.
Time course EPI of human brain function during task activation.
Megn Reson Med.
1992;
25
390-398
- 25
Belliveau JW, Kennedy DN, McKinstry RC, Buchbinder BR, Weisskopf RM, Cohen MS, Vevea JM,
Brady TJ, Rosen BR.
Functional mapping of the human visual cortex by magnetic resonance imaging.
Science.
1991;
254
716-719
- 26
Bock C, Schmitz B, Kerskens CM, Gyngell ML, Hossmann K-A, Hoehn-Berlage M.
Functional MRI of somatosensory activation in rat: effect of hypercapnic up-regulation
on perfusion and BOLD-imaging.
Magn Res Med.
1998;
39
457-461
- 27
Kwong KK, Belliveau JW, Chesler DA, Goldberg IE, Weisskopf RM, Pourcelot RM, Kennedy DN,
Hoppel BE, Cohen MS, Turner R, Cheng HM, Brady TJ, Rosen BR.
Dynamic magnetic resonance imaging of human brain activity during primary sensory
stimulation.
Proc Natl Acad Sci USA.
1992;
89
5675-5679
- 28
Logothetis NK, Guggenberger H, Peled S, Pauls J.
Functional imaging of the monkey brain.
Nature neuroscience.
1999;
555-562
- 29
Raichle ME.
Behind the scenes of functional brain imaging: a historical and physiological perspective.
Proc Natl Acad Sci USA.
1998;
95
765-772
- 30
Gsell W, de Sadeleer C, Marchalant Y, MacKenzie ET, Schumann P, Dauphin F.
The use of cerebral blood flow as an index of neuronal activity in functional neuroimaging:
experimental and pathophysiological considerations.
J Chem Neuroanatom.
2000;
20
215-224
- 31
Terborg C, Gora F, Weiller C, Röther J.
Reduced vasomotor reactivity in cerebral microangiopathy.
Stroke.
2000;
31
924-929
- 32
Ringelstein EB, Nabavi DG.
Cerebral small vessel diseases: cerebral microangiopathies.
Curr Opin Neurol.
2005;
18
179-188
- 33
Kiechl S, Willeit J.
The natural course of atherosclerosis; Part I: incidence and progression.
Arterioscler Thromb Vasc Biol.
1999;
19
1484-1490
- 34
Bakker SLM, de Leeuw FE, de Groot JC, Hofman A, Koudstaal PJ, Breteler MMB.
Cerebral vasomotor reactivity and cerebral white matter lesions in the elderly.
Neurology.
1999;
52
578-583
- 35
Evora PRB.
An open discussion about endothelial dysfunction: Is it timely to propose a classification?.
Int J Cardiol.
2000;
73
289-292
- 36
Gorelick PB, Sacco RL, Smith DB, Alberts M, Mustone-Alexander L, Rader D, Ross JL,
Raps E, Ozer MN, Brass LM, Malone ME, Goldberg S, Booss J, Hanley DF, Toole JF, Greengold NL,
Rhew DC.
Prevention of a first stroke.
JAMA.
1999;
281
1112-1110
- 37
Cupini LM, Diomedi M, Placidi F, Silvestrini M, Giacomini P.
Cerebrovascular reactivity and subcortical infarctions.
Arch Neurol.
2001;
58
577-581
- 38
Ross R.
The pathogenesis of atherosclerosis: a perspective for the 1990s.
Nature.
1993;
70
111-118
- 39
Guy CN, Ffytche DH, Brovelli A, Chumillas J.
fMRI and EEG responses to periodic visual stimulation.
Neuroimage.
1999;
10
125-148
- 40
Gotoh J, Kuang T-Y, Nakao Y, Cohen DM, Melzer P, Itoh Y, Pak H, Pettigrew K, Sokoloff L.
Regional differences in mechanisms of cerebral circulatory response to neuronal activation.
Am J Physiol Heart Circ Physiol.
2001;
280
H821-H829
- 41 Conrad B, Klingelhöfer J. Influence of complex visual stimuli on the regional cerebral
blood flow. In: Deecke L, Eccles JC, Mountcastle VB (Eds.)
From neuron to action. New York, Springer 1990: 277-281
- 42
Conrad B, Klingelhöfer J.
Dynamics of regional cerebral blood flow for various visual stimuli.
Exp Brain Res.
1989;
77
437-441
- 43
Aaslid R.
Visually evoked dynamic blood flow response of the human cerebral circulation.
Stroke.
1987;
18
771-775
- 44
Rosengarten B, Molnar S, Trautmann J, Kaps M.
Simultaneous VEP and transcranial Doppler ultrasound recordings to investigate activation-flow
coupling in humans.
Ultrasound Med Biol.
2006;
32
1171-1180
- 45
Obrig J, Israel H, Kohl-Bareis M, Uludag K, Wenzel R, Müller B, Arnold G, Villringer A.
Habituation of the visually evoked potential and ist vascular response: implications
for neurovascular coupling in the healthy adult.
Neuroimage.
2002;
17
1-18
- 46
Zaletel M, Strucl M, Rodi Z, Zvan B.
The relationship between visually evoked cerebral blood flow velocity responses and
visual-evoked potentials.
Neuroimage.
2004;
22
1784-1789
- 47
DiRusso F, Martinez A, Sereno MI, Pitzalis S, Hillyard SA.
Cortical sources of the early components of the visual evoked potential.
Hum Brain Mapp.
2002;
15
95-111
- 48
Stockard JJ, Iragui VJ.
Clinical useful applications of evoked potentials in adult neurology.
J Clin Neurophys.
1984;
1
159-202
- 49
Gomez SM, Gomez CR, Hall IS.
Transcranial Doppler ultrasonographic assessment of intermittent light stimulation
at different frequencies.
Stroke.
1990;
21
1746-1748
- 50
Rosengarten B, Budden C, Osthaus S, Kaps M.
Effect of heart rate on regulative features of the cortical activity-flow coupling.
Cerebrovasc Dis.
2003a;
16
47-52
- 51
Azevedo E, Rosengarten B, Santos R, Freitas J, Kaps M.
Interplay of cerebral autoregulation and neurovascular coupling evaluated by functional
TCD in different orthostatic conditions.
J Neurol.
, im Druck
- 52
Rosengarten B, Huwendiek O, Kaps M.
Neurovascular coupling and cerebral autoregulation can be described in terms of a
control system.
Ultrasound Med Biol.
2001b;
27
189-193
- 53
Rosengarten B, Lutz H, Hossmann KA.
A control system approach for evaluating somatosensory activation by laser-Doppler
flowmetry in the rat cortex.
J Neurosci Methods.
2003b;
130
75-81
- 54
Iadecola C.
Regulation of the cerebral microcirculation during neural activity: is nitric oxide
the missing link?.
Trends Neurosci.
1993;
16
206-214
- 55
Iadecola C, Pelligrino DA, Moskowitz MA, Lassen NA.
Nitric oxide synthase inhibition and cerebrovascular regulation.
J Cereb Blood Flow Metab.
1994;
14
175-192
- 56
Buerk DG, Ances BM, Greenberg JH, Detre JA.
Temporal dynamics of brain tissue nitric oxide during functional forepaw stimulation
in rats.
Neuroimage.
2003;
18
1-9
- 57
Baron AD.
Vascular reactivity.
Am J Cardiol.
1999;
84
25J-27J
- 58
Rosengarten B, Dost A, Kaufmann A, Gortner L, Kaps M.
Impaired cerebrovascular reactivity in Type-1 diabetic children.
Diabetes Care.
2002c;
25
408-410
- 59
Aaslid R, Markwalder TM, Nornes H.
Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral
arteries.
J Neurosurg.
1982;
57
769-774
- 60
Becker VU, Hansen HC, Brewitt U, Thie A.
Visually evoked cerebral blood flow velocity changes in different states of brain
dysfunction.
Stroke.
1996;
27
446-449
- 61
Kontos HA.
Validity of cerebral arterial blood flow calculations from velocity measurements.
Stroke.
1989;
20
1-3
- 62
Rosengarten B, Aldinger C, Kaufmann A, Kaps M.
Comparison of visually evoked peak systolic and end diastolic blood flow velocity
using a control system approach.
Ultrasound Med Biol.
2001;
27
1499-1503
- 63
Rosengarten B, Kaps M.
Peak systolic velocity doppler index reflects most appropriately the dynamic time
course of intact cerebral autoregulation.
Cerebrovasc Dis.
2002;
13
230-234
- 64
Katzman R.
Alzheimer's disease.
N Engl J Med.
1986;
314
964-973
- 65
Patrella JR, Coleman RE, Doraiswamy PM.
Neuroimaging and early diagnosis of Alzheimer disease: a look to the future.
Radiology.
2003;
226
315-336
- 66
Park L, Anrather J, Forster C, Kazama K, Carlson GA, Iadecola C.
A [beta]- induced vascular oxidative stress and attenuation of functional hyperemia
in mouse somatosensory cortex.
J Cereb Blood Flow Metab.
2004;
24
334-342
- 67
Abramov AY, Canevari L, Duchen MR.
Beta-amyloid peptides induce mitochondrial dysfunction and oxidative stress in astrocytes
and death of neurons through activation of NADPH oxidase.
J Neurosci.
2004;
24
565-575
- 68
Kono I, Mori S, Nakajima K, Nakagawa M, Watanabe Y, Kizu O, Yamada K, Sakai Y.
Do white matter changes have clinical significance in Alzheimer's disease.
Gerontology.
2004;
50
242-246
- 69
Rosengarten B, Paulsen S, Molnar S, Kaschel R, Gallhofer B, Kaps M.
Activation-flow coupling differentiates between vascular and Alzheimer type of dementia.
J Neurol Sci.
2000;
, im Druck
- 70
Rosengarten B, Paulsen S, Molnar S, Kaschel R, Gallhofer B, Kaps M.
Acetylcholine esterase inhibitor donepezil improves dynamic cerebrovascular regulation
in Alzheimer patients.
J Neurol.
2006;
253
58-64
- 71
Bartus RT, Dean 3rd RL, Beer B, Lippa AS.
The cholinergic hypothesis of geriatric memory dysfunction.
Science.
1982;
217
408-417
- 72
Rosengarten B, Schermuly RT; Voswinckel R, Kohstall MG, Olschewski H, Weissmann N,
Seeger W, Kaps M, Grimminger F, Ghofrani HA.
Sildenafil improves dynamic vascular function in the brain: studies in patients with
pulmonary hypertension.
Cerebrovasc Dis.
2006;
21
194-200
Korrespondenzadresse
PD Dr. med. B. Rosengarten
Universitätsklinikum Giessen und Marburg GmbH
Standort Giessen
Klinik für Neurologie
Am Steg 14
35392 Giessen
Email: bernhard.rosengarten@neuro.med.uni-giessen.de