Research

Funding: DFG, 335.000 EUR

Project Details:
The equine recurrent uveitis (ERU) is the most important eye disease in horses, but the exact pathogenesis is still not fully understood. Furthermore, the recurrent uveitis is also found in human as well as almost all domesticated animals. Since autoreactive antibodies are detectedable in diseased horses, the classical ERU is considered as an autoimmune disease. The classical form of ERU is characterized by an acute serofibrinous and plasmacellular inflammation of the ciliary body, iris, choroidea and other eye structures. The disease often results into a chronic form by recurring intervallic relapses. The impulses lead to a progressive destruction of intraocular structures and finally lead to blindness.
Besides autoimmune processes, Leptospira infections are discussed to contribute to ERU in humans, horses, dogs and cattle. In over 60% of ERU-diseased horses Leptospira interrogans has been detected in the VBF using PCR or microscopic agglutination test (MAT). Additionally, the microbiological culture of Leptospira interrogans from VBF has been proven in further studies. Nevertheless, the role of the pathogen in the pathogenesis of ERU is still controversially discussed. Since the eye is protected via special barriers as one of the immune-privileged compartments in the body, the immigration of protective immune cells into the eye is highly regulated. A damage of the blood retina barrier is a typical pathological feature of ERU and often leads to a large number of migrating immune cells into the eye. The question arises whether the barrier is disrupted by infectious agents such as Leptospira, or whether the infection is a consequence of the immune-mediated pathogenesis of the ERU. These questions have not been fully clarified yet. However, irrespective of the Leptospira detection in ERU-diseased horses, the pathogenesis of ERU seems to be a highly complex altered immune reaction of the eye. Interestingly, in some populations an accumulation of different leukocyte populations as granulocytes can also be found in ERU patients, which have been histologically detected in the retina. However, especially the role of neutrophil granulocytes in ERU is still unclear and the focus of this project.

Results:

Neutrophil Extracellular Traps in the Pathogenesis of Equine Recurrent Uveitis (ERU).

Fingerhut L, Ohnesorge B, von Borstel M, Schumski A, Strutzberg-Minder K, Mörgelin M, Deeg CA, Haagsman HP, Beineke A, von Köckritz-Blickwede M, de Buhr N.

Cells. 2019 Nov 27;8(12). pii: E1528. doi: 10.3390/cells8121528.

 

Fingerhut L, Dolz G, de Buhr N. 2020. What Is the Evolutionary Fingerprint in Neutrophil Granulocytes? Int J Mol Sci 21:1-37.

 

Fingerhut L, Yücel L, Struzberg-Minder K, von Köckritz-Blickwede M, Ohnesorge B, de Buhr N. 2022. Ex Vivo and In Vitro Analysis Identify a Detrimental Impact of Neutrophil Extracellular Traps on Eye Structures in Equine Recurrent Uveitis. Front Immunol 13:1-20.

Cooperation Partners:

Prof. Dr. Cornelia Deeg, Philipps Universität Marburg, FB Medizin, Experimentelle Ophthalmologie, Marburg

Prof. Dr. Andreas Beineke, Institute for Pathology, TiHo

Dr. Katrin Strutzberg-Minder, IVD, Hannover, Germany

Prof. Dr. Henk Haagsman, Department of Infectious Diseases & Immunology, Division Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Netherlands

Funding: DFG, 329.905 EUR

Project Details:
The VIPER research and training program will cover the global chain of events involved in virus emergence, all the way from virus discovery, isolation, molecular characterization, surveillance, and pathogenesis, towards animal and public health impact and intervention strategies including new approaches for prevention and control.

The VIPER research projects are subdivided into three pillars:

virus discovery, host range and transmission
virus-host cell interactions and pathogenesis, and
immune interference and intervention strategies.

Project Details:
Several studies, including those of our research groups, have shown that certain inflammatory mediators including neutrophil extracellular traps (NETs) and DNase activity may be of relevance during and after stroke. Therefore, we analyse human cohorts to identify new insights in this research topic.

Results:

Grosse GM, Blume N, Abu-Fares O, Götz F, Ernst J, Leotescu A, Gabriel MM, van Gemmeren T, Worthmann H, Lichtinghagen R, Imker R, Falk CS, Weissenborn K, Schuppner R, de Buhr N. 2022. Endogenous Deoxyribonuclease Activity and Cell-Free Deoxyribonucleic Acid in Acute Ischemic Stroke: A Cohort Study. Stroke 53.

Cooperation Partners:

Cerebrovascular Research Group (Head: Prof. Dr. Karin Weissenborn), Dept. of Neurology, MHH: Dr. Ramona Schuppner & Dr. Gerrit M. Grosse, Dr. Maria Gabriel, PD Dr. Hans Worthmann

Funding: DFG, 329.905 EUR

Project Details:
The VIPER research and training program will cover the global chain of events involved in virus emergence, all the way from virus discovery, isolation, molecular characterization, surveillance, and pathogenesis, towards animal and public health impact and intervention strategies including new approaches for prevention and control.

The VIPER research projects are subdivided into three pillars:
virus discovery, host range and transmission
virus-host cell interactions and pathogenesis, and
immune interference and intervention strategies.

Funding: DFG, 329.905 EUR

Project Details:
The VIPER research and training program will cover the global chain of events involved in virus emergence, all the way from virus discovery, isolation, molecular characterization, surveillance, and pathogenesis, towards animal and public health impact and intervention strategies including new approaches for prevention and control.

The VIPER research projects are subdivided into three pillars:

virus discovery, host range and transmission
virus-host cell interactions and pathogenesis, and
immune interference and intervention strategies.

Funding: DFG, 329.905 EUR

Project Details:
The VIPER research and training program will cover the global chain of events involved in virus emergence, all the way from virus discovery, isolation, molecular characterization, surveillance, and pathogenesis, towards animal and public health impact and intervention strategies including new approaches for prevention and control.

The VIPER research projects are subdivided into three pillars:

virus discovery, host range and transmission
virus-host cell interactions and pathogenesis, and
immune interference and intervention strategies.

Funding: DFG, 329.905 EUR

Project Details:
The VIPER research and training program will cover the global chain of events involved in virus emergence, all the way from virus discovery, isolation, molecular characterization, surveillance, and pathogenesis, towards animal and public health impact and intervention strategies including new approaches for prevention and control.

The VIPER research projects are subdivided into three pillars:

virus discovery, host range and transmission
virus-host cell interactions and pathogenesis, and
immune interference and intervention strategies.

Funding: Deutsche Forschungsgemeinschaft, 354.500 EUR

Project Details:
Etwa 30% aller Epilepsie-Patienten gelten als pharmakoresistent, d.h. sie zeigen Anfälle trotz optimal eingesetzter Antiepileptika. Klinisch angewendete Alternativen zur systemischen Pharmakotherapie sind limitiert, z.B. die chirurgische Fokusresektion durch multifokale Epilepsien oder durch eine unklare Fokuslage. Die Entwicklung alternativer Behandlungsstrategien wie der intrazerebralen Pharmakotherapie mit einer zielgerichteten Modulation fokusferner Schlüsselregionen des epileptischen Netzwerks stellt daher eine bedeutsame Herausforderung in der Epilepsietherapie dar. Unter Umgehung der Blut-Hirn-Schranke können dabei lokal im Gehirn höhere Wirkstoffkonzentrationen erreicht werden und dabei systemische Nebenwirkungen minimiert werden. Ziel des Projekts ist die Weiterentwicklung der intrazerebralen Mikroinfusion rational ausgewählter Wirkstoffe mit unterschiedlichem Wirkmechanismus zur zielgerichteten Behandlung pharmakoresistenter Epilepsien.

Results:

MacKeigan D., Feja M., Gernert M. (2024) Chronic intermittent convection-enhanced delivery of vigabatrin to the bilateral subthalamic nucleus in an acute rat seizure model. Epilepsy Res. 199:107276.

[doi: 10.1016/j.eplepsyres.2023.107276]

 

MacKeigan D., Feja M., Meller S., Deking L., Javadova A., Veenhuis A., Felmy F., Gernert M. (2023) Long-lasting antiseizure effects of chronic intrasubthalamic convection-enhanced delivery of valproate. Neurobiol. Dis. 187:106321.

[doi: 10.1016/j.nbd.2023.106321]

 

Gernert M., MacKeigan D., Deking, L., Kaczmarek E., Feja M. (2023) Acute and chronic convection-enhanced muscimol delivery into the rat subthalamic nucleus induces antiseizure effects associated with high responder rates. Epilepsy Res. 190:107097.

[doi: 10.1016/j.eplepsyres.2023.107097]

 

Feja M., Meller S., Deking L.S., Kaczmarek E., During M.J., Silverman R.B., Gernert M. (2021) OV329, a novel highly potent γ-aminobutyric acid aminotransferase inactivator, induces pronounced anticonvulsant effects in the pentylenetetrazole seizure threshold test and in amygdala-kindled rats. Epilepsia 62:3091-3104.

[doi: 10.1111/epi.17090]

https://doi.org/10.3390/pharmaceutics12121134

Cooperation Partners:

Prof. Dr. Richard B. Silverman (Dept. of Chemistry, Northwestern University, Evanston, IL; U.S.A.)

Matthew J. During (Ovid Therapeutics, New York, New

York, USA)

Funding: EU, 295.313 EUR

Project Details:
Untersuchung von Mechanismen und Modellen, die die Zugänglichkeit von Therapeutika (IM2PACT) für das Gehirn vorhersagen

Funding: Gesellschaft der Freunde, 18.000 EUR

Project Details:
In human medicine caesarean section seemed to be a risk factor for the development of immunologic and metabolic diseases in children, which can be partially counteracted with "vaginal seeding", the exposure of the offspring to maternal vaginal fluids directly after caesarean section. The aim of this study was to investigate the effect of "vaginal seeding" on early calf health born via caesarean section.

Cooperation Partners:

FLI Braunschweig, Institut für Tierernährung, Prof. Deanicke, F. Billenkamp