The project aims at understanding the molecular and biochemical mechanisms, by which the brain adapts local blood flow to metabolism with high temporal and spatial resolution. In addition, we are investigating the 'fingerprints' of physiological
or pathophysiological processes in cerebral blood flow or hemoglobin oxygenation. These studies thereby provide the basis for modern non-invasive functional brain imaging methods (e.g. fMRI, NIRS), which utilize brain blood flow changes or
oxygenation changes to map brain activity. Our models include brain slices, isolated arteries as well as cell culture, while functional activation studies are conducted with near infrared spectroscopy (optical imaging), laser Doppler Flowmetry, and
electrophysiological methods in animal experiments and in humans (somatosensory stimulation).
Dr.Ute Lindauer, Prof.Dr.Ulrich Dirnagl, Dr.Jens Dreier, Dr. Christoph Leithner,
Dr.Gabor Petzold, Dr. Georg Royl, Dr.Sigrid Schuh-Hofer, Dr.Heike Sellien
Dreier J, Petzold G,Tille K, Lindauer U, Arnold G, Heinemann U, Einhäupl
K, Dirnagl U (2002) Ischaemia triggered by red blood cell products in the
subarachnoid space is inhibited by nimodipine or moderate volume expansion/hemodilution
in rats. Neurosurgery 51:1457-1467, 2002
Dreier JP, Sakowitz OW, Harder A, Zimmer C, Dirnagl U, Valdueza JM, Unterberg
AW (2002) Focal laminar cortical MR-signal abnormalities after subarachnoid
hemorrhage: report of two cases. Ann Neurol 52:825-9
Dreier J, Kleeberg, Priller J, Petzold G, Windmuller O, Orzechowski, Kohl
M, Lindauer U, Heinemann U, Victorov IV, Einhaupl KM, Dirnagl U (2002) Endothelin
-1 potently induces Leao's spreading depression in vivo in the rat: a model
for an endothelial trigger of migrainous aura? Brain 125: 102-112
Dreier U, Petzold G, Tille K, Lindauer U, Arnold G, Heinemann U, Einhäupl
KM, Dirnagl U Ischaemia triggered by spreading neuronal activation is inhibted
by vasodilators in rats J Physiol (London ) (2001) 531.2:515-526
Lindauer U, Royl G, Kühl M, Leithner C, Gold L, Gethmann J, Kohl M, Villringer
A, Dirnagl U. No evidence for early decrease in blood oxygenation in rat whisker
cortex in response to functional activation Neuroimage (2001) 13: 988-1001
Lindauer U, Kunz A, Schuh-Hofer S, Vogt J, Dreier JP, Dirnagl U (2001):
Nitric oxide from perivascular nerves modulates cerebral arteriolar pH reactivity.
Am J Physiol 281:H1353-H1363
Kohl M., Ute Lindauer, Georg Royl, Marc Kühl, Lorenz Gold, Arno Villringer,
Ulrich Dirnagl. Physical Model for the Spectroscopic Analysis of Cortical
Intrinsic Optical Signals. Phys Med Biol (2000) 45:3749-64
Wenzel R, Wobst P, Heekeren HH, Kwong KK, Brandt SA, Kohl M, Obrig H, Dirnagl
U, Villringer A. Saccadic supression induces focal hypoxygenation in the occipital
cortex. J Cereb Blood Flow Metab. (2000) 20:1103-1110
Dreier JP, Ebert N, Priller J, Megow D, Lindauer U, Klee R, Reuter U, Imai
Y, Einhäupl KM, Victorov I, Dirnagl U. Products of hemolysis in the subarachnoid
space induce cortical spreading ischemia and focal necrosis in rats, a model
for delayed ischemic neurological deficits after subarachnoid hemorrhage?
J Neurosurg (2000) 93(4):658-66
Lindauer U., D. Megow, H. Matsuda, and U. Dirnagl (1999) Nitric Oxide: a
modulator, but not a mediator of neurovascular coupling in somatosensory cortex
of rats. Am J Physiol 277: H799-H811
Valdueza JM, Draganski B, Hoffmann O, Dirnagl U, Einhaupl KM Analysis of
CO2 Vasomotor Reactivity and Vessel Diameter Changes by Simultaneous Venous
and Arterial Doppler Recordings (1999) Stroke 30:81-86
Heekeren HR, Kohl M, Obrig H, Wenzel R, Pannwitz Wv, Matcher SJ, Dirnagl
U, Cooper CE, Villringer A (1999) Noninvasive assessment of changes in cytochrome-C-oxydase
in human subjects during visual stimulation J Cereb Blood Flow 19:592-603
Reuter, U., J. R. Weber, L. Gold, G. Arnold, T. Wolf, J. Dreier, U. Lindauer,
and U. Dirnagl. Locally triggered release of neurotransmitters from perivascular
nerves contributes to cortical spreading depression associated hyperemia in
rats. Am J Physiol 274(6): H1979-H1987, 1998
Malonek, D., U. Dirnagl, U. Lindauer, K. Yamada, I. Kanno, and A. Grinvald.
Vascular imprints of neuronal activity: Relationships between the dynamics
of cortical blood flow, oxygenation, and volume changes following sensory
stimulation. Proc.Natl.Acad.Sci.U.S.A. 94(26):14826-31, 1997.
Wolf T, Lindauer U, Villringer A, Dirnagl U. Excessive oxygen or glucose
supply do not alter the blood flow response to somatosensory stimulation or
spreading depression in rats. Brain Res 1997;761(2):290-299
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.
Barfod, C., Akgören, N., Fabricius, M., Dirnagl, U., and Lauritzen, M. Erythrocyte
recruitment during hypo- and hypercapnia and locally evoked increases of cerebral
blood flow. Acta Physiol Scand (1997) 160:123-132.
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
Kleinschmidt, A., Obrig, H., Requardt, M., Merboldt, K.D., Dirnagl, U.,
Villringer, A., Frahm, J. Simultaneous recording of cerebral oxygenation changes
during human brain activation by magnetic resoncance imaging and near - infrared
spectroscopy. J. Cereb Blood Flow Metab 16: 817-827 (1996).
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
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
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.
Villringer A., Them, A., Lindauer, U., Dirnagl U. Capillary perfusion of
the rat brain cortex: An in vivo microscopy study (1994) Circ Res 75:55-62
Niwa,K., Lindauer, U., Villringer, A., Dirnagl, U. (1993) Blockade of nitric
oxide synthesis in rats strongly attenuates the CBF-response to extracellular
acidosis. J Cereb Blood Flow Metab 13:535-539
Lindauer, U., Villringer, A. & Dirnagl, U. (1993) Characterisation of
the cerebral blood flow response to somatosensory stimulation: model and influence
of anesthesia. Am J Physiol 264:H1223-H1228.
Villringer, A., Planck, J., Hock, C., Schleinkofer, L. & Dirnagl, U.
(1993) Near infrared spectroscopy (NIRS): A new tool to study hemodynamic
changes during activation of brain function in human adults. Neurosci Lett
154:101-104
Dirnagl U, Lindauer U, Villringer A (1993) Role of nitric oxide in the coupling
of cerebral blood flow to neuronal activation in rats. Neurosci Lett 149:
43-46
Dirnagl U, Villringer A, Gebhardt R, Haberl RL, Einhäupl KM (1991) Three
dimensional reconstruction of the rat brain cortical microcirculation in vivo.
J Cereb Blood Flow Metab 11:352-360.
We are investigating systemic, biochemical, and molecular mechanisms of focal cerebral ischemia (stroke). A particular focus is on endogenous mechanisms of protection (ischemic tolerance, preconditioning) and on delayed mechanisms of damage
(inflammation, apoptosis). We employ cell culture (hypoxia/aglycemia) and in vivo (thread occlusion, hook etc,.) models of stroke. In these model systems physiological (LDF, NIRS, confocal microscopy in vivo), biochemical (HPLC, chemoluminescence
etc.), and molecular biological (PCR, SAGE, etc.) techniques are utilized. It is the ultimate goal of these studies to further our understanding on the pathophysiological cascades of damage in stroke, and thereby to develop new avenues of
treatment.
Ruscher K, Freyer D, Karsch M, Isaev N, Megow D, Sawitzki B, Priller J,
Dirnagl U, Meisel A. (2002) Erythropoietin: a paracrine mediator of ischemic
tolerance in the brain - Evidence from an in vitro model of cerebral ischemia.
J. Neuroscience 22:10291-301
Kapinya KJ, Prass K, Dirnagl U (2002) Isoflurane induced prolonged protection
against cerebral ischemia in mice - a redox sensitive mechanism? Neuroreport
13:1431-5
Kapinya KJ, Löwl D, Fütterer C, Maurer M, Waschke KF, Isaev NK, Dirnagl
U (2002) Tolerance against ischemic neuronal injury can be induced by volatile
anesthetics and is iNOS-dependent. Stroke 33:1889-1898
Trendelenburg G, Prass K, Priller J, Kapinya K, Polley A, Muselmann C, Ruscher
K, Kannbley U, Schmitt AO, Castell S, Wiegand F, Meisel A, Rosenthal A, Dirnagl
U (2002) Serial analysis of gene expression identifies metallothionein II
as major neuroprotective gene in mouse focal cerebral ischemia. J Neurosci
22:5879-5888
Prass K, Ruscher, Karsch M, Isaev N, Megow D, Priller J, Scharff A, Dirnagl
U, and Meisel A (2002) Desferrioxamine induces delayed tolerance against cerebral
ischemia in vivo and in vitro. J Cereb Blood Flow Metab 22:520-525
Priller, J. Alexander Flügel, Tim Wehner, Matthias Boentert, Carola A. Haas,
Marco Prinz, Francisco Fernández-Klett, Konstantin Prass, Ingo Bechmann, Bauke
A. de Boer, Michael Frotscher, Georg W. Kreutzberg, Derek A. Persons, Ulrich
Dirnagl (2001) Targeting of gene-modified hematopoietic cells to the central
nervous system: use of the green fluorescent protein uncovers microglial engraftment.
Nature Med 7:1356-1361
Priller J., Persons DA, Fernandez-Klett F, Kempermann G, Kreutzberg GW,
Dirnagl U (2001) Neogenesis of cerebellar Purkinje neurons from gene-marked
hematopoetic stem cells in vivo. J Cell Biol 155:733-8
Endres M., Fan G., Meisel A., Dirnagl U, Jaenisch R. Effects of cerebral
ischemia in mice lacking DNA methyltransferase 1 in postmitotic neurons (2001)
Neuroreport 12:3763-3766
Katchanov J, Christoph Harms, Karen Gertz, Ludger Hauck, Christian Waeber,
Lorenz Hirt, Josef Priller, Rüdiger von Harsdorf , Wolfgang Brück, Heide Hörtnagl,
Ulrich Dirnagl, Pradeep G. Bhide, and Matthias Endres (2001) Mild cerebral
ischemia induces loss of cyclin dependent kinase inhibitors and activation
of cell cycle machinery prior to delayed neuronal cell death. J Neurosci 21:5045-53.
Harms C, Marion Lautenschlager, Alexandra Bergk, Juri Katchanov, Dorette
Freyer, Krisztian Kapinya, Ulrike Herwig, Dirk Megow, Ulrich Dirnagl, Joerg
R. Weber, Heide Hörtnagl (2001) Differential mechanisms of neuroprotection
by 17 b-estradiol in apoptotic versus necrotic neurodegeneration. J Neurosci
(2001) 21:2600-2609
Weih M., Nicola Amberger, Susanne Wegener, Ulrich Dirnagl, Thomas Reuter,
and Karl Einhaupl (2001) Sulfonylurea drugs do not influence initial stroke
severity and in-hospital outcome in stroke patients with diabetes. Stroke
2001;32 2029-2032
Weih M, Schmitt M, Gieche J , Harms C, Dirnagl U ; Grune T (2001) Proteolysis
of oxidized proteins after oxygen-glucose deprivation in rat cortical neurons
is mediated by the proteasome. J Cereb Blood Flow Metab 21:1090-1096
Laufs U, Gertz K, Huang P, Nickenig G, Bohm M, Dirnagl U, Endres M. Atorvastatin
upregulates Type III NO synthase in thrombocytes, decreases platelet activation,
and protects from cerebral ischemia in normocholesteremic mice. Stroke (2000)
31:2437-2449
Lyons SA, Pastor A, Ohlemeyer C, Kann O, Wiegand F, Prass K, Knapp F, Kettenmann
H and Dirnagl U. Distinct physiological properties of microglia and blood
born cells in rat brain slices after permanent middle cerebral artery occlusion.
J Cereb Blood Flow Metab (2000) 20:1537-49
Endres M, Meisel A, Biniszkiewicz M, Namura S, Prass K, Ruscher K, Lipski
A, Jaenisch R, Moskowitz MA, Dirnagl U. DNA methyltransferase contributes
to delayed ischemic brain injury J Neurosci (2000) 20:3175-3181
Endres M, Fink K, Zhu J, Stagliano NE, Bondada V, Geddes JW, Azuma T, Mattson
MP, Kwiatkowski DJ, Moskowitz MA Neuroprotective effects of gelsolin during
murine stroke. J Clin Invest 1999 Feb;103(3):347-54
Harms C, Lautenschlager M, Bergk A, Freyer D, Weih M, Dirnagl U, Weber JR,
Hörtnagl H. Melatonin is protective in necrotic but not in caspase-dependent,
free radical-independent apoptotic neuronal cell death in primary neuronal
cultures FASEB J (2000) 14:1814-1824
Prass K, Wiegand F, Schumann P, Ahrens M, Kapinya K, Harms C, Liao W, Trendelenburg
G, Gertz K, Moskowitz MA, Knapp F, Victorov IV, Megow D, Dirnagl U. Hyperbaric
oxygenation induced tolerance against focal cerebral ischemia in mice is strain
dependenent. Brain Res (2000) 871:146-150
Ruscher K., Reuter M., Kupper D., Trendelenburg G., Dirnagl U., Meisel A.
A fluorescence based non radioactive electrophoretic mobility shift assay.
J Biotechnol (2000) 78:163-170
Weih M., Kallenberg K., Bergk A., Dirnagl U., Harms L., Einhäupl K.M. (1999)
Attenuated stroke severity after prodromal TIA: A role for ischemic tolerance
in the brain? Stroke Stroke (1999) 30:1851-1854.
Wiegand F., W. Liao, C. Busch, S. Castell, F. Knapp, U. Lindauer, D. Megow,
A. Meisel, A. Redetzky, K. Ruscher, G. Trendelenburg, I. V. Victorov, M. Riepe,
H. C. Diener, and U. Dirnagl (1999) Respiratory chain inhibition induces tolerance
to focal cerebral ischemia. J .Cereb.Blood Flow Metab. 19:1229-37
Victorov Ilya V., Konstantin Prass, Ulrich Dirnagl. Improved selective,
simple, and contrast staining of acidophilic neurons with vanadium acid fuchsin.
Brain Res Protocols (2000) in press
Weih M, Bergk A, Isaev NK, Ruscher K, Megow D, Riepe M, Meisel A, Victorov
IV and Dirnagl U. Induction of ischemic tolerance in rat cortical neurons
by 3-nitropropionic acid: chemical preconditioning, Neurosci Lett (1999) 272:207-210
Dirnagl U, Iadecola C, Moskowitz MA (1999) Pathobiology of ischemic stroke:
an integrative view. Trends Neurosci 22:391-397
Prass K, Dirnagl U. Glutamate antagonists in the therapy of stroke. Restor
Neurol Neurosci (1998) 13:3-11
Ruscher K., Isaev N, Trendelenburg G, Weih M, Iurato L, Meisel A, Dirnagl
U Induction of hypoxia inducible factor 1 by oxygen glucose deprivation is
attenuated by hypoxic preconditioning in rat cultured neurons (1998). Neurosci
Lett 254(2):117-20.
Turski L, Huth A, Neuhaus R, McDonald F, Schneider H, Sheardown M, Dirnagl
U, Wiegand F, Jacobsen P, Ottow E (1998). Phosphonate quinoxalinediones for
neuroprotection in ischemia and head trauma Proc Natl Acad Sci USA 1998; 95(18):10960-10965
Dreier J. P., K. Körner, N. Ebert, A. Görner, I. Rubin, T. Back, U. Lindauer,
T. Wolf, A. Villringer, K. M. Einhäupl, M. Lauritzen, and U. Dirnagl. Nitric
oxide scavenging by hemoglobin or nitric oxide synthase inhibition by N-nitro-L-arginine
induce cortical spreading ischemia when K+ is increased in the subarachnoid
space. J.Cereb.Blood Flow Metab. (1998) Sep;18(9):978-990.
Peters O, Back T, Lindauer U, Busch C, Megow D, Dreier J, Dirnagl U. (1998)
Increased formation of reactive oxygen species following permanent and reversible
middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 18:196-205
Wolf T, Lindauer U, Reuter U, Back T, Dirnagl U. Noninvasive near infrared
spectroscopy monitoring of regional cerebral blood oxygenation changes during
periinfarct depolarizations in focal cerebral ischemia in the rat. J Cereb
Blood Flow Metab (1997) 17:950-954
Bruer, U., Isaev, N.K., Weih, M., Ruscher, K., Bergk, A., Wiegand, F., Meisel,
A., Victorov, I.V., and Dirnagl, U. (1997) Induction of ischemic tolerance
in rat cortical neurons: hypoxic versus pharmacologic preconditioning. FEBS
Letters 414(1), 117-121 (1997)
Riepe, M., Nakase, H., Esclaire, F., Kaschischke, K., Schreiber, S., Ludolph,
A.C., Dirnagl, U., Hugon, J., and Kempski, O. Chemical preconditioning: neuroprotection
by chemical inhibition of oxidative phosphorylation. J. Cereb. Blood. Flow.
Metab. 1997, 17: 257-264
Dirnagl U., Lindauer U., Them A., Schreiber S., Pfister H.W., Koedel U.,
Reszka R., Freyer D., Villringer A. Global cerebral ischemia in the rat: Online
monitoring of oxygen free radical production using chemoluminescence in vivo
(1995) J Cereb Blood Flow and Metab 15:929-940,1995
Dirnagl, U., Niwa, K. Sixt, G., Villringer, A. (1994) Cortical hypoperfusion
after global forebrain ischemia in the rat is not caused by microvascular
leukocyte plugging. Stroke 25:1028-1038
Dirnagl U, Thorén P, Villringer A, Sixt G, Them A, Einhäupl K (1993) Global
forebrain ischemia in the rat: controlled reduction of cerebral blood flow
by hypobaric hypotension and two-vessel occlusion. Neurol Res 15:128-130
Dirnagl U, Pulsinelli W (1990) Autoregulation of cerebral blood flow in
experimental focal brain ischemia. J Cereb Blood Flow Metab. 10:327-336.
Dirnagl U, Kaplan B, Jacewicz M, Pulsinelli W (1989) Continuous measurement
of cerebral cortical blood flow by laser-Doppler flowmetry in a rat stroke
model. J.Cereb.Blood Flow Metab. 9:589-596.
Despite antibiotic treatment bacterial meningitis of the adult has a high morbidity and mortality. An improvement of this situation is not expected from develpment of new antibiotics, but rather from the development of adjunctive therapy
targeting the mechanisms of damage of inflammation. The project focusses on a systemic, cellular, and molecular level at the mechanisms that are triggered by the contact of bacterial components and which ultimately lead to brain tissue
destruction.
Braun JS, Sublett JE, Freyer D, Mitchell TJ, Cleveland JL, Tuomanen EI,
Weber JR. Pneumococcal pneumolysin and H(2)O(2) mediate brain cell apoptosis
during meningitis. J Clin Invest. 2002 Jan;109(1):19-27.
Braun JS, Novak R, Murray PJ, Eischen CM, Susin SA, Kroemer G, Halle A,
Weber JR, Tuomanen EI, Cleveland JL. Related Articles Apoptosis-inducing factor
mediates microglial and neuronal apoptosis caused by pneumococcus. J Infect
Dis. 2001 Nov 15;184(10):1300-9.
Hanisch UK, Prinz M, Angstwurm K, Hausler KG, Kann O, Kettenmann H, Weber
JR. Related Articles The protein tyrosine kinase inhibitor AG126 prevents
the massive microglial cytokine induction by pneumococcal cell walls. Eur
J Immunol. 2001 Jul;31(7):2104-15.
Hoffmann O, Dirnagl U, Weber JR. Related Articles The trigeminovascular
system in bacterial meningitis. Microsc Res Tech. 2001 May 1;53(3):188-92
Angstwurm K, Reuss S, Freyer D, Arnold G, Dirnagl U, Schumann RR, Weber
JR. Induced hypothermia in experimental pneumococcal meningitis. J Cereb Blood
Flow Metab (2000) 20:834-838
Freyer D, Manz R, Ziegenhorn A, Weih M, Angstwurm K, Docke WD, Meisel A,
Schumann RR, Schonfelder G, Dirnagl U, Weber JR. Cerebral endothelial aells
release TNF-a after stimulation with cell walls of streptococcus pneumoniae
and regulate inducible nitric oxide synthase and ICAM-1 expression via autocrine
loops. J Immunol (1999) 163: 4308-4314.
Draheim HJ, Prinz M, Weber JR, Weiser T, Kettenmann H, Hanisch UK Induction
of potassium channels in mouse brain microglia: cells acquire responsiveness
to pneumococcal cell wall components during late development. Neuroscience
1999;89(4):1379-90
Braun JS, Novak R, Herzog KH, Bodner SM, Cleveland JL, Tuomanen EI Neuroprotection
by a caspase inhibitor in acute bacterial meningitis. Nat Med 1999 Mar;5(3):298-302
Prinz M, Kann O, Draheim HJ, Schumann RR, Kettenmann H, Weber JR, Hanisch
UK Microglial activation by components of gram-positive and -negative bacteria:
distinct and common routes to the induction of ion channels and cytokines.
J Neuropathol Exp Neurol 1999 Oct;58(10):1078-89
Angstwurm K, Freyer D, Dirnagl U, Hanisch UK, Schumann RR, Einhaupl KM,
Weber JR. Tumour necrosis factor alpha induces only minor inflammatory changes
in the central nervous system, but augments experimental meningitis. Neuroscience
1998 Sep;86(2):627-34
Weber JR, Rosenkranz T, Angstwurm W, Lindauer U, Freyer D, Bürger W, Einhäupl
K, Dirnagl U. Histamine (H1) receptor antagonist inhibits leukocyte rolling
in pial vessels in the early phase of bacterial meningitis. Neurosci Lett
226(1), 17-20 (1997)
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.748:1-11,
1997
Weber, J. R., Angstwurm, K., Bove, G. M., Bürger, W., Einhäupl, K. M., Dirnagl,
U., and Moskowitz, M. A. The trigeminal nerve augments regional cerebral blood
flow during experimental bacterial meningitis. J. Cereb. Blood. Flow. Metab.
16 (1996):1319-1325
Weber, J., Angstwurm.K., Bürger,W. Einhäupl, K.M., Dirnagl, U. Anti ICAM-1
monoclonal antibody reduces inflammatory changes in experimental bacterial
meningitis. J.Neuroimmunol. (1995) 63: 63-68
Freyer, D., Weih,M., Weber, J., Manz R, Ziegenhorn, A., Angstwurm,K., Bürger,W.,
Dirnagl U. Pneumococcal cell wall components induce nitric oxide synthase
and TNFa in astroglial enriched cultures. Glia (1996) 16:1-6
Angstwurm C, Weber,J., Segert,A.,Bürger,W.,Weih,M.,Freyer,D., Einhäupl K.M.,Dirnagl,
U. Fucoidin, a polysaccaride inhibiting leukocyte rolling, attenuates inflammatory
responses in experimental pneumococcal meningitis in rat. Neurosci Lett 190:1-4,1995
Pfister HW, Ködel U, Haberl RL, Dirnagl U, Feiden W, Ruckdeschel G, Einhäupl
K (1990) Microvascular changes during the early phase of experimental bacterial
meningitis. J Cereb Blood Flow Metab 10:914-922.
Pfister HW, Ködel U, Dirnagl U, Haberl RL, Feiden W, Einhäupl KM (1990)
Superoxide dismutase inhibits brain oedema formation in experimental pneumococcal
meninigitis. Acta Neurochir 51:378-380.
Headache is the most frequent neurological disorder. We are investigating pathophysiological
mechanisms related to the development of migraine in experimental animal models
and in vitro with a particular interest in nitric oxide (NO). Our studies are
designed to determine mechanisms by which NO activates pain sensitive trigeminal
neurons. We are also trying to elucidate as to whether NO plays a role in sensitization
of trigeminal c-fibers, a phenomenon recently described in migraineurs. In ordert
to assess these questions we use immunohistological, biochemical and molecular
biological techniques. In a second area of interest we are focussing on mechanisms
by which oxygen aborts cluster headache in an animal model.
Reuter U, Chiarugi A, Bolay H, Moskowitz MA. Nuclear factor-kappaB as a
molecular target for migraine therapy. Ann Neurol. 2002 Apr;51(4):507-16.
Bolay H, Reuter U, Dunn AK, Huang Z, Boas DA, Moskowitz MA. Intrinsic brain
activity triggers trigeminal meningeal afferents in a migraine model. Nat
Med. 2002 Feb;8(2):136-42.
Reuter U, Bolay H, Jansen-Olesen I, Chiarugi A, Sanchez del Rio M, Letourneau
R, Theoharides TC, Waeber C, Moskowitz MA. Delayed inflammation in rat meninges:
implications for migraine pathophysiology. Brain. 2001 Dec;124(Pt 12):2490-502.
Reuter U, Sanchez del Rio M, Moskowitz MA. Experimental models of migraine.
Funct Neurol. 2000;15 Suppl 3:9-18. Review.
Sanchez del Rio M, Reuter U, Moskowitz MA. Central and peripheral mechanisms
of migraine. Funct Neurol. 2000;15 Suppl 3:157-62. Review.
O. Hoffmann, N. Keilwerth, M Bastholm Bille, D Freyer, U.Reuter, U.Dirnagl,
R. Schumann and JR Weber. Selective 5HT 1B/D agonists reduce the inflammatory
response in bacterial meningitis. J Cereb Blood Flow Metab. 2002, in press
Schuh-Hofer S, Lobsien E, Brodowsky R, Vogt J, Dreier JP, Klee R, Dirnagl
U, Lindauer U. The cerebrovascular response to elevated potassium--role of
nitric oxide in the in vitro model of isolated rat middle cerebral arteries.
Neurosci Lett. 2001 Jun 22;306(1-2):61-4.
Dreier JP, Ebert N, Priller J, Megow D, Lindauer U, Klee R, Reuter U, Imai
Y, Einhaupl KM, Victorov I, Dirnagl U. Products of hemolysis in the subarachnoid
space inducing spreading ischemia in the cortex and focal necrosis in rats:
a model for delayed ischemic neurological deficits after subarachnoid hemorrhage?
J Neurosurg. 2000 Oct;93(4):658-66.
Schuh-Hofer S, Reuter U, Kinze S, Einhaupl KM, Arnold G.Treatment of acute
cluster headache with 20 mg sumatriptan nasal spray--an open pilot study.
J Neurol. 2002 Jan;249(1):94-9.
Arnold G, Reuter U, Kinze S, Wolf T, Einhaupl KM. Migraine with aura shows
gadolinium enhancement which is reversed following prophylactic treatment.
Cephalalgia. 1998 ov;18(9):644-6.
Reuter U, Weber JR, Gold L, Arnold G, Wolf T, Dreier J, Lindauer U, Dirnagl
U. Perivascular nerves contribute to cortical spreading depression-associated
hyperemia in rats.Am J Physiol. 1998 Jun;274(6 Pt 2):H1979-87.
Gold L, Back T, Arnold G, Dreier J, Einhaupl KM, Reuter U, Dirnagl U. Cortical
spreading depression-associated hyperemia in rats: involvement of serotonin.
Brain Res. 1998 Feb 9;783(2):188-93.
Wolf T, Lindauer U, Reuter U, Back T, Villringer A, Einhaupl K, Dirnagl
U. Noninvasive near infrared spectroscopy monitoring of regional cerebral
blood oxygenation changes during peri-infarct depolarizations in focal cerebral
ischemia in the rat. J Cereb Blood Flow Metab. 1997 Sep;17(9):950-4
Please check out some of the projects in more detail in the project
section.