Professor Jens P. Dreier, M.D.

Research Group Dreier

Professor Jens P. Dreier, M.D.
Charité, Center for Stroke Research Berlin
Translation in Stroke Research


Dr. Dreier is a professor at the CSB and a consultant at the Department of Neurology at the Charité. His scientific focus has for many years been on clinical and neurophysiological aspects of neurovascular coupling, spreading depolarization, regional cerebral blood flow, ischemic stroke, aSAH, epilepsy and migraine.

List of Publications / Charité Research Data Base

Selected Publications

The negative ultraslow potential, electrophysiological correlate of infarction in the human cortex.
Lückl J, Lemale CL, Kola V, Horst V, Khojasteh U, Oliveira-Ferreira AI, Major S, Winkler MKL, Kang EJ, Schoknecht K, Martus P, Hartings JA, Woitzik J, Dreier JP.
Brain. 2018 Apr 16. doi: 10.1093/brain/awy102. [Epub ahead of print]

Terminal spreading depolarization and electrical silence in death of human cerebral cortex.
Dreier JP, Major S, Foreman B, Winkler MKL, Kang EJ, Milakara D, Lemale CL, DiNapoli V, Hinzman JM, Woitzik J, Andaluz N, Carlson A, Hartings JA.
Ann Neurol. 2018 Feb;83(2):295-310. doi: 10.1002/ana.25147. Epub 2018 Feb 15.

Subarachnoid blood acutely induces spreading depolarizations and early cortical infarction.
Hartings JA, York J, Carroll CP, Hinzman JM, Mahoney E, Krueger B, Winkler MKL, Major S, Horst V, Jahnke P, Woitzik J, Kola V, Du Y, Hagen M, Jiang J, Dreier JP.
Brain. 2017 Oct 1;140(10):2673-2690. doi: 10.1093/brain/awx214.

The stroke-migraine depolarization continuum.
Dreier JP, Reiffurth C.
Neuron. 2015 May 20;86(4):902-22. doi: 10.1016/j.neuron.2015.04.004. Review.

The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease.
Dreier JP.
Nat Med. 2011 Apr;17(4):439-47. doi: 10.1038/nm.2333. Review.


More than 50 % of the overall stroke mortality is caused by cerebral haemorrhages. The so-called aneurysmal subarachnoid haemorrhage (aSAH) represents about 30 % of these. Typically, patients are young (average age ~50 years). Aneurysmal SAH is often followed by a delayed ischemic stroke and today we know that delayed ischemia is responsible for about 6 to 7 % of all severe disabilities and deaths among aSAH patients. The therapeutic options to prevent delayed ischemic stroke are few (hyperdynamic therapy), and associated with life-threatening complications such as heart failure and pulmonary edema. I therefore think that it is mandatory to assign only those patients to therapy who develop delayed ischemia. This treatment stratification must occur at the earliest possible time point before delayed brain damage becomes irreversible. I would like to provide new instruments to diagnose delayed ischemic stroke in a very early time window and thus evaluate new therapeutic options

Most Important Project

Protect brain

DISCHARGE-I - Depolarizations in ISCHaemia after subARachnoid haemorrhaGE

DISCHARGE-1 is a prospective, clinical, multicenter, ISRCTN-registered, diagnostic trial (Berlin [PIs: Dreier, Vajkoczy], Heidelberg, Frankfurt, Cologne, Beer-Sheva) of the COSBID study group.
More information/project description

Further Projects

Spreading Ischemia and the Negative Ultraslow Potential
Spreading depolarization (SD) is associated with a dilatation of cerebral resistance vessels/ increase of cerebral blood flow in healthy tissue. More than a decade ago, we discovered in rats that this normal neurovascular coupling can be inverted under conditions present following aneurysmal subarachnoid haemorrhage (aSAH). Thus, the neuronal discharge triggered severe vasoconstriction/ spreading ischemia in the rat. In 2009 we published unequivocal evidence for spreading ischemia in the human brain using novel technology for the first time to measure electrical activity and regional cerebral blood flow in aSAH patients. Our recently published article in Brain (doi:10.1093/brain/awy102; further underscores that spreading ischemia is of outstanding clinical importance. This is because spreading ischemia may lead to the so called negative ultraslow potential (NUP). The NUP is initiated by SD and similar to the negative direct potential (DC) shift of prolonged SD, but specifically refers to a negative potential component during progressive recruitment of neurons into cell death in the wake of SD. In the paper, we first quantified the SD-initiated NUP in the DC range and the activity depression in the alternate current (AC) range of the electrocorticogram after middle cerebral artery occlusion in rats. Relevance of these variables to the injury was supported by significant correlations with the cortical infarct volume and neurological outcome after 72 hours of survival. We then identified NUP-containing clusters of SDs in 11 patients with aSAH. We found that NUP-displaying electrodes were significantly more likely to overlie a developing ischemic lesion than those not displaying a NUP. The NUP was often preceded by an SD cluster with increasingly persistent spreading depressions and progressively prolonged DC shifts and spreading ischemias. During the NUP, spreading ischemia lasted for 40.0 (median) (28.0, 76.5, interquartile range) min, cerebral blood flow fell from 57 (53, 65) % to 26 (16, 42) % and the tissue partial pressure of oxygen from 12.5 (9.2, 15.2) to 3.3 (2.4, 7.4) mmHg. Our data suggested that the NUP is the electrophysiological correlate of infarction in human cerebral cortex and a neuromonitoring-detected medical emergency. Currently, we perform more human and animal research to learn more about the underlying mechanisms of spreading ischemia and NUP.


'Normal' and 'Inverse' Neurovascular Coupling to Spreading Depolarization

Spreading depolarization (SD) occurs in the brain's gray matter when passive cation influx across the cellular membranes exceeds ATP-dependent Na+ and Ca2+ pump activity ( This leads to near-complete breakdown of the neuronal ion gradients and depolarization of neurons and astrocytes, followed by neuronal swelling and cessation of neuronal function. This mass tissue depolarization propagates through gray matter as a wave, or 'brain tsunami', at ~3 mm/min, and is measured as a slow negative shift, 10-20 mV in amplitude, of the extracellular direct current (DC) potential. SD is a passive process, driven by electrical and diffusion forces. Subsequent repolarization, however, increases energy consumption because additional Na+ and Ca2+ pumps are recruited to correct their harmful intracellular surge. Thus, even in healthy tissue where full repolarization of cellular membranes is achieved within 1-2 min, ATP falls ~50%. To increase oxygen and glucose availability, SD induces dilatation of resistance vessels in healthy tissue. Hence, regional cerebral blood flow (rCBF) increases in response to SD resulting in spreading hyperemia, a process which is termed 'normal' neurovascular coupling. The opposite of the 'normal' neurovascular  response, termed 'inverse' neurovascular coupling, occurs when there is local dysfunction of the microvasculature. With 'inverse' coupling, severe microvascular spasm instead of vasodilation is coupled to SD, resulting in spreading ischemia. The perfusion deficit of spreading ischemia in turn prolongs the neuronal depolarization since the oxygen-/glucose deprivation further reduces ATP availability (Dreier et al., 1998; Dreier et al., 2000; Windmüller et al., 2005). This is reflected by a prolongation of both the negative DC potential shift and the silencing of neuronal activity. Pharmacologically induced spreading ischemia was sufficient to produce widespread focal necrosis in absence of a preceding significant perfusion deficit in rats. This suggested that 'inverse' neurovascular coupling is (i) a sufficient condition for SD to induce cell death, and, thus (ii) a promising target for therapeutic intervention.


Sebastian Major
Sebastian Major
Clemens Reiffurth
Clemens Reiffurth
Karl Schoknecht
Karl Schoknecht
Coline Lemale
Coline Lemale


Clinical Trials

Design and conduction of diagnostic and interventional mono-/ multicentric trials in patients with aneurysmal subarachnoid hemorrhage, stroke or migraine. Neuromonitoring on the neurocritical care unit.

Animal Models

Cranial window models using imaging and microelectrodes; human and animal brain slice models; histology, immunohistochemistry, MRI

Cooperations and Research Partners

  • COSBID study group
  • Prof. Heiner Audebert, Charité Berlin, Deutschland
  • Dr. Baptiste Balança, Centre de Recherches en Neurosciences de Lyon, France
  • Prof. Ulrich Dirnagl, Charité Berlin, Deutschland
  • Prof. Wolfram Döhner, Charité Berlin, Deutschland
  • Prof. Matthias Endres, Charité Berlin, Deutschland
  • Prof. Alon Friedman, Beer-Sheva, Israel and Halifax, Kanada
  • Prof. Jed Hartings, University of Cincinnati, Ohio, USA
  • Prof. Christoph Harms, Charité Berlin, Deutschland
  • Dr. Nils Hecht, Charité Berlin, Deutschland
  • Dr. Agustin Liotta, Charité Berlin, Deutschland
  • Dr. Stephane Marinesco, Centre de Recherches en Neurosciences de Lyon, France
  • Prof. Peter Martus, Tübingen, Deutschland
  • Prof. Andreas Meisel, Charité Berlin, Deutschland
  • Prof. Josef Priller, Charité Berlin, Deutschland
  • PD Dr. Michael Scheel, Charité Berlin, Deutschland
  • Prof. Ilan Shelef, Beer-Sheva, Israel
  • Dr. Bob Siegerink, Charité Berlin, Deutschland
  • Prof. Peter Vajkoczy, Charité Berlin, Deutschland
  • PD Dr. Johannes Woitzik, Charité Berlin, Deutschland
  • Dr. Stefan Wolf, Charité Berlin, Deutschland
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