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 Research Groups

 Neuropharmacology

Prof. Dr. Klaus G. Reymann

Head:

Prof. Dr. Klaus G. Reymann

Department Neurochemistry and Molecular Biology
Leibniz Institute for Neurobiology
Brenneckestraße 6
39118 Magdeburg
Germany
Phone: +49-391-6263-93441
Fax: +49-391-626393439
E-mail:

The research of our “Project group Neuropharmacology” is focused on the pathophysiology and pharmacology of cerebral ischemia and Alzheimer dementia. Some of our ongoing projects are realized in close collaboration with the DZNE Magdeburg and the Research Institute for Applied Neurosciences (FAN gGmbH).

Stem cell transplantation: An ischemic insult is the result of an insufficient blood flow within the brain, followed by failures of function, disability and dementia. Thus, it is a prevalent disease and also the third-most reason for death. To date, there is no common pharmacological neuroprotection after an ischemic insult in clinics. So far the only reliable therapy after stroke is thrombolysis in specific patients. Thus, there is a huge importance to improve motor skills and cognitive functionality after an insult. During the last decade the literature has shown that even in the adult brain a formation of new neurons can occur. We focus on possible regeneration after an ischemic insult, based on proliferation, migration and functional integration of endogenous stem cells as well as transplanted adult stem cells. We investigate the post-ischemic mechanisms of regeneration and neuronal plasticity in rodent tissue cultures and in behavioral models. In collaboration with European partners we have finished the EU STEMS project. We were able to show that mesenchymal and induced human pluripotent stem cells (iPS-cells) differentiate into neurons after transplantation into rats after experimental stroke.

Immune cells and stroke: The acute inflammatory reaction in the early phase of stroke is accompanied by the activation of microglia, resident brain specific immune cells, and the recruitment of peripheral leucocytes, especially neutrophils and monocytes/macrophages. We focused on the nature and function of interactions between microglia and invading immune cells. In the past we could identify a new neuroprotective mechanism of the CNS whereby microglia guards neurons by engulfment of toxic neutrophil granulocytes invading brain slices under ischemic conditions. We are now investigating the post-ischemic changes of microglial morphology and the infiltration of neutrophils into the ischemic penumbra using intracranial live imaging via two-photon microscopy. Until now we found a rapid extravasation of neutrophils after ischemia and dramatic changes of microglia morphology in the first 24 h after experimental stroke. We are now visualizing the immune cross-talk directly within vital tissue using intracranial 2-photon microscopy.

Human cerebral small vessel disease (CSVD): CSVD or microangiopathy, one of the leading causes of cerebral (lacunar) ischemia and white matter lesions, is not only associated with stroke-like symptoms, but also with cognitive impairments that occur in vascular dementia. The underlying histopathology of the cerebral microangiopathy includes degenerative vessel wall changes, microbleeds and blood brain barrier (BBB) disturbances. Our results reveal that the vascular pathology in SHRSP proceeds in definite stages, whereas an age-dependent accumulation of erythrocytes in capillaries and arterioles represents the homogeneous initial step of the disease. Those early erythrocyte accumulations are followed by subsequent BBB disturbances and microbleeds, both also increasing with age. Finally, microthromboses develop as a reaction to microbleeds and this leads to ischemic cell death. Erythrocyte accumulations without cerebral tissue damage represent the first step of vascular pathology in SHRSP. If that initial phenomenon could also be identified in patients, those erythrocyte accumulations might be a promising target for implementing prophylactic and therapeutic strategies in human CSVD.

Amyloid-oligomers and dementia: The increased life expectancy of people in industrialized nations is linked to a rise in age-related illnesses, most notably neurodegenerative diseases such as Alzheimer's dementia. The disturbances of neuronal function induced by sublethal Aβ concentrations are hypothesized to be the first stages of the cognitive decline in patients. It is known that Aß oligomerization leads to the impairment of long-term potentiation, a form of synaptic memory. With electrophysiological techniques in hippocampal slices we investigate the mechanisms and related drug targets of amyloid ß-induced functional disturbances testing synaptic plasticity (long term potentiation-LTP). Several Aβ-oligomer species were shown to reduce the synaptic memory, number of spines and network activity long before any cell death occurs. In collaboration with Drs. Goldschmidt, Ohl and Scheich (LIN) we now use Thallium-autometallography and small animal-SPECT for the investigation of cortical network aspects of the β-amyloid-pathology.

Annual Report:

 

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last update: 2013-06-17 report a bug print this page