As part of the SFB 1270/2 ELAINE (ELektrisch Aktive ImplaNtatE), we are investigating the effects of deep brain stimulation in the treatment of the hyperkinetic movement disorder dystonia in an interdisciplinary environment. We use patch-clamp, field potential and high-resolution microelectrode array measurements to investigate the influence of the electric field on neuronal network activity and synaptic transmission.

Key publications

• Franz, D, Richter, A, and Köhling, R. (2023). Electrophysiological insights into deep brain stimulation of the network disorder dystonia. Pflugers Arch. 2023 Oct;475(10):1133-1147. PMID: 37530804.
• Stefanie Perl, Anika Lüttig, Rüdiger Köhling, Angelika Richter. Deep brain stimulation in animal models of dystonia.Neurobiol Dis. 2022 Oct 25;105912. PMID: 36307031
   
• Paap, M., Perl, S., Lüttig, A., Plocksties, F., Niemann, C., Timmermann, D., Bahls, C., van Rienen, U., Franz, D., Zwar, M., Rohde, M., Köhling, R., Richter, A., 2020. Deep brain stimulation by optimized stimulators in a phenotypic model of dystonia: Effects of different frequencies. Neurobiol Dis 105163. PMID: 33166698
   
• Heerdegen M, Zwar M, Franz D, Hörnschemeyer J, Neubert V, Plocksties F, Niemann C, Timmermann D, Bahls C, van Rienen U, Paap M, Perl S, Lüttig A, Richter A, Köhling R. Mechanisms of pallidal deep brain stimulation: alteration of cortico-striatal synaptic communication in a dystonia animal model.Neurobiol Dis. 2021 Mar 19;105341. PMID: 33753292

Contact
Prof. Dr. Rüdiger Köhling
Dr. Denise Franz
Dr. Marco Heerdegen

The institute's research in computational neuroscience is based on close collaboration with the Institute of Mathematics and the group of Prof. Jens Starke, as well as the Institute of Theoretical Electrical Engineering and the group of Prof. Ursula van Rienen, as part of the SFB 1270 ELAINE.
Our joint work focuses on improving deep brain stimulation (DBS) as a treatment for neurological disorders such as dystonia and Parkinson's disease. By developing large-scale computer models, the team simulates neuronal networks, particularly in the basal ganglia and thalamo-cortical systems, to understand how DBS can modulate brain activity. These models incorporate biophysical dynamics and connectivity data to identify optimal stimulation targets (‘sweet spots’) and parameters. Key innovations include the definition of new biomarkers for therapy evaluation, such as the ratio of single action potentials to action potential series in the thalamus, and the determination of the influence of different stimulation frequencies on network behaviour. The research integrates structural and functional brain data to identify effective target areas for DBS and to understand the collective dynamics of the network. The results will help to understand the mechanisms of DBS in movement disorders and to open up further fields of therapy, e.g. also for the treatment of non-motor symptoms.

Key publications

• Spiliotis K, Butenko K, van Rienen U, Starke J, Köhling R. Complex network measures reveal optimal targets for deep brain stimulation and identify clusters of collective brain dynamics.Front. Phys. 2022; 10:951724. DOI: 10.3389/fphy.2022.951724
   
• Butenko K, Köhling R, Van Rienen. U. Numerical study on electrode design for rodent deep brain stimulation with implantations cranial to targeted nuclei.Front Comput Neurosci. 2021 Feb 2;15:631188. PMID: 33603655
   
• Spiliotis K, Starke J, Franz D, Richter A, Köhling R. Deep brain stimulation for movement disorder treatment: exploring frequency-dependent efficacy in a computational network model. Biol Cybern. 2021 Dec 11. PMID: 34894291
   
• Plocksties F, Kober M, Niemann C, Heller J, Fauser M, Nüssel M, Uster F, Franz D, Zwar M, Lüttig A, Kröger J, Harloff J, Schulz A, Richter A, Köhling R, Timmermann D, Storch A. The software defined implantable modular platform (STELLA) for preclinical deep brain stimulation research in rodents. J Neural Eng. 2021 Sep 21;18(5). PMID: 34542029

Contact
Prof. Dr. Rüdiger Köhling
Prof. Dr. Jens Starke

The research focus of ‘clinical physiology’ encompasses various organ systems and diseases.

Urinary bladder
Overactive bladder syndrome, with the typical symptoms of imperative urinary urgency with or without urge incontinence, is a common disease in the aging population. The pharmacotherapeutic approach centres on micturition-inhibiting anticholinergics, but treatment is still unsatisfactory. In a cooperative project with the Department of Urology, we are investigating contractile mechanisms of the detrusor muscle in order to identify age-dependent changes.

Colon
Hirschsprung's disease is a malformation in the terminal part of the colon, characterised by the absence of intramural ganglia. This results in intestinal obstruction, which requires surgical treatment. In cooperation with the Department of Paediatric Surgery, we examine human surgical resections to gain a better understanding of the disease and identify possible therapeutic approaches.

Cortex
Human brain tissue that has to be removed during tumour surgery provides a unique opportunity to study the structure and function of the human cortex. In cooperation with the Department of Neurosurgery, we are establishing the electrophysiological examination of human brain slices from surgical resections.

Key publications

• Madadi A, Wolfart J, Lange F, Brehme H, Linnebacher M, Bräuer AU, Büttner A, Freiman T, Henker C, Einsle A, Rackow S, Köhling R, Kirschstein T, Müller S. Correlation between Kir4.1 expression and barium-sensitive currents in rat and human glioma cell lines.Neurosci Lett. 2021 Jan 10;741:135481. PMID: 33161102
   
• Mader F, Müller S, Krause L, Springer A, Kernig K, Protzel C, Porath K, Rackow S, Wittstock T, Frank M, Hakenberg OW, Köhling R, Kirschstein T. Hyperpolarization-Activated Cyclic Nucleotide-Gated Non-selective (HCN) Ion Channels Regulate Human and Murine Urinary Bladder Contractility.Front. Physiol. 2018; 9: 753. PMID: 29971015
   
• Petereit C, Porath K, Rackow S, Kernig K, Hakenberg OW, Köhling R, Kirschstein T. Age-dependent effects of the β3 adrenoceptor agonist CL316,243 on human and rat detrusor muscle strips.Pflugers Arch. 2024 Feb;476(2):243-256. PMID: 37993748

Contact
Prof. Dr. Timo Kirschstein
Prof. Dr. Rüdiger Köhling

Temporal lobe epilepsy is the most common form of focal epilepsy and is often refractory to therapy. We use various animal models to gain a better understanding of the pathophysiology of this disease and to develop new therapeutic approaches. We are also trying to identify antiepileptogenic strategies to positively influence the course of the disease.

Key publications

• Schulze F, Müller S, Guli X, Schumann L, Brehme H, Riffert T, Rohde M, Goerss D, Rackow S, Einsle A, Kirschstein T, Köhling R. CK2 Inhibition Prior to Status Epilepticus Persistently Enhances KCa2 Function in CA1 Which Slows Down Disease Progression.Front. Cell. Neurosci. 2020; 14: 33. PMID: 32174814
   
• Küpper M, Porath K, Sellmann T, Bien CG, Köhling R, Kirschstein T. GluN2B inhibition rescues impaired potentiation and epileptogenicity at associational-commissural CA3 synapses in a model of anti-NMDAR encephalitis.Neurosci. Lett. 2023; 795: 137031. PMID: 36574811

Contact
Prof. Dr. Timo Kirschstein
Prof. Dr. Rüdiger Köhling

Ischemic cerebral infarction, characterized by impaired cerebral blood flow and a resulting lack of oxygen and energy substrates, is the most common cause of stroke, accounting for approximately 85% of all strokes. Current treatment options are limited to recanalizing therapy within a very short time frame. In our research group, we investigate the pathomechanisms of ischemic stroke using the tMCAO mouse model. This in vivo model, which mimics an infarction of the middle cerebral artery, is particularly well-suited to simulating the human disease, as it allows for both hypoperfusion and reperfusion and also allows for the consideration of vascular and immunological processes. Our research group also uses an ex vivo OGD model to investigate neurocellular changes during and after ischemia using electrophysiological measurements on acute brain slices. This model is particularly well-suited to analyzing the neuroprotective effects of various drugs, thereby laying the foundation for future clinical trials.

Key publications

• Henze L, Walter U, Murua Escobar H, Junghanss C, Jaster R, Köhling R, Lange F, Salehzadeh-Yazdi A, Wolkenhauer O, Hamed M, Barrantes I, Palmer D, Möller S, Kowald A, Heussen N, Fuellen G. Towards biomarkers for outcomes after pancreatic ductal adenocarcinoma and ischaemic stroke, with focus on (co)-morbidity and ageing/cellular senescence (SASKit): protocol for a prospective cohort study.BMJ Open. 2020 Dec 17;10(12):e039560. PMID: 33334830

Contact
Prof. Dr. Rüdiger Köhling
Prof. Dr. Timo Kirschstein
Dr. Gesine Reichart

Radiotherapy is one of the three mainstays of cancer treatment, alongside surgical removal and chemotherapy. Spatially fractionated irradiation (so-called microbeam radiotherapy) is a new form of radiotherapy that can treat the tumour more effectively than conventional radiotherapy because of the higher radiation dose. We are particularly interested in the radiobiological consequences for the risk organs, so we are investigating the effects of microbeam therapy on various organs in cooperation with the Clinic for Radiotherapy.

Key publications

• Lange F, Kirschstein T, Davis J, Paino J, Barnes M, Klein M, Porath K, Stöhlmacher P, Fiedler S, Frank M, Köhling R, Hildebrandt G, Hausermann D, Lerch M, Schültke E. Microbeam Irradiation of the Beating Rodent Heart: An Ex Vivo Study of Acute and Subacute Effects on Cardiac Function.Int. J. Radiat. Oncol. Biol. Phys. 2022; 114(1): 143-152. PMID: 35533907
   
• Schültke E, Lerch M, Kirschstein T, Lange F, Porath K, Fiedler S, Davis J, Paino J, Engels E, Barnes M, Klein M, Hall C, Häusermann D, Hildebrandt G. Modification of the Langendorff system of the isolated beating heart for experimental radiotherapy at a synchrotron: 4000 Gy in a heart beat.J. Synchrotron Radiat. 2022; 29(Pt 4): 1027-1032. PMID: 35787570
   
• Frerker B, Fiedler S, Kirschstein T, Lange F, Porath K, Sellmann T, Kutzner L, Wilde F, Moosmann J, Köhling R, Hildebrandt G, Schültke E. Effects of Microbeam Irradiation on Rodent Esophageal Smooth Muscle Contraction.Cells 2022; 12(1): 176. PMID: 36611969

Contact
Prof. Dr. Timo Kirschstein
Dr. Falko Lange

Glioblastomas are the most common type of brain tumour. With a median survival time of about 15-18 months after diagnosis, they have one of the most unfavourable prognoses of any type of cancer. About half of all brain tumour patients suffer from symptomatic epilepsy at the time of diagnosis. One in three patients with a malignant brain tumour who do not show any epileptic seizures at diagnosis develop symptomatic epilepsy over time. This makes malignant brain tumours one of the most dreaded types of cancer, not only because of their unfavourable prognosis, but also because of the impairment of quality of life and cognitive functions. In interdisciplinary projects, we are primarily investigating the mode of action of drugs and signalling pathway mediators that influence both tumour progression and tumour-associated epilepsy from a pathophysiological point of view, with the aim of establishing new therapeutic approaches.

Key publications

• Lange F, Gade R, Einsle A, Porath K, Reichart G, Maletzki C, Schneider B, Henker C, Dubinski D, Linnebacher M, Köhling R, Freiman TM, Kirschstein T. A glutamatergic biomarker panel enables differentiating Grade 4 gliomas/astrocytomas from brain metastases.Front Oncol. 2024 May 21:14:1335401. PMID: 38835368

• Lange F, Hartung J, Liebelt C, Boisserée J, Resch T, Porath K, Hörnschemeyer J, Reichart G, Sellmann T, Neubert V, Kriesen S, Hildebrandt G, Schültke E, Köhling R, Kirschstein T. Perampanel add-on to standard radiochemotherapy in vivo promotes neuroprotection in a rodent F98 glioma model.Front Neurosci. 2020 Nov 30;14:598266. PMID: 33328869
   
• Lange F, Weßlau K, Porath K, Hörnschemeyer J, Bergner C, Krause BJ, Mullins CS, Linnebacher M, Köhling R, Kirschstein T. AMPA receptor antagonist perampanel affects glioblastoma cell growth and glutamate release in vitro.PLoS One. 2019 Feb 4;14(2):e0211644. PMID: 30716120

Contact
Prof. Dr. Rüdiger Köhling
Prof. Dr. Timo Kirschstein
Dr. Falko Lange

The invasive behaviour of tumour cells is often a reason for a poor prognosis. One tumour-promoting factor is potentially represented by direct current electric fields, which arise primarily from transepithelial potentials. Our own research focuses on the galvanotaxis, the directed migration along these electrical fields, of brain tumour cells and cells of gastrointestinal tumour entities, in order to gain a better understanding of the pathophysiology of these diseases.

Key publications

• Lange F, Porath K, Sellmann T, Einsle A, Jaster R, Linnebacher M, Köhling R, Kirschstein T. Direct-Current Electrical Field Stimulation of Patient-Derived Colorectal Cancer Cells.Biology. 2023 Jul 22;12(7):1032. PMID: 37508461
   
• Lange F, Venus J, Shams Esfand Abady D, Porath K, Einsle A, Sellmann T, Neubert V, Reichart G, Linnebacher M, Köhling R, Kirschstein T. Galvanotactic Migration of Glioblastoma and Brain Metastases Cells. Life (Basel). 2022 Apr 14;12(4):580. PMID: 35455071

Contact
Prof. Dr. Timo Kirschstein
Dr. Falko Lange

We use electrophysiological measurements (including patch-clamp, galvanotaxis, impedance measurement) to investigate the effects of electrical and mechanical stimulation, which are used to treat bone and cartilage defects, on the membrane and ion channel properties of cells in the tissue.

Key publications

• Engel N, Dau M, Engel V, Franz D, Klemmstein F, Thanisch C, Kolb JF, Frank M, Springer A, Köhling R, Bader R, Frerich B, Wiesmann N, Heimes D, Kämmerer PW. Combining Electrostimulation with Impedance Sensing to Promote and Track Osteogenesis within a Titanium Implant. Biomedicines. 2023 Feb 24;11(3):697. PMID: 36979676
   
• Rohde M, Ziebart J, Kirschstein T, Sellmann T, Porath K, Kühl F, Dalenda B, Bahls C, Van Rienen U, Bader R, Köhling R. Human osteoblast migration in DC electrical fields depends on store-operated Ca2+-release and is correlated to upregulation of stretch-activated TRPM7 channels. Front Bioeng Biotechnol. 2019 Dec 12;7:422. PMID: 31921825
   
• Dawson JE, Sellmann T, Porath K, Bader R, van Rienen U, Appali R, Köhling R. Cell-cell interactions and fluctuations in the direction of motility promote directed migration of osteoblasts in direct current electrotaxis. Front Bioeng Biotechnol. 2022 Oct 6;10:995326. PMID: 36277406

Contact
Prof. Dr. Rüdiger Köhling
PD. Dr. Nadja Engel
Dr. Denise Franz