Principle investigators: Kathrin Baldauf, Holger Braun

A focal cerebral ischemia, induced by the insertion of a filament in the middle cerebral artery or the occlusion of the artery by endothelin-1, leads to a damage of cortical and striatal brain areas. A „repair“ of these damaged areas might be possible by activating endogenous stem cells or by transplantation of exogenous stem cells. An increase of the endogenous cell proliferation was shown in the subventricular zone after the application of different factors such as growth factors or antiapototic substances. To what extent these factors can prevent the cells from death and/or lead the cells towards a neuronal differentiation, is the topic of the current investigations.

Embryonic stem cells (ES-cells) as well as bone marrow cells are investigated for transplantation purposes after stroke. We showed that ES-cells are able to survive in the infarcted area of the rat brain. Further, they differentiated into neurons and glia, demonstrating that ES-cells can at least partly and for limited time replace lost neurons and astrocytes after stroke. Bone marrow cells are migrating to the lesion site and probably release trophic factors supporting the regeneration of the insulted brain.

Results:

We have shown that

1. 2 weeks after eMCAO BrdU-positive cells are identified in the striatum, in the lateral ventricle wall and in the dentate gyrus of the hippocampus
2. growth factors such as EGF/bFGF increase the number of BrdU-positive and DCX-positive cells in the lateral ventricle
3. ischemia has no effect on the cell number in the ventricle wall, but increases the number of BrdU-positive cells in the striatum
4. transplanted embryonic stem cells (ES-cells) survive in the necrotic area of the ischemic brain and differentiate into neurons and astrocytes

NISSL-staining of the lesioned side of the ischemic brain (left) und double labelling of BrdU (green) and DCX (red) in the subventricular zone and in the lateral ventricle wall.

Transplanted cells have been differentiated into astrocytes. Astrocytes are identified by green labelled GFP and red labelled GFAP.

References:

Baldauf K, Reymann KG. (2005) Influence of EGF/bFGF treatment on proliferation, early neurogenesis and infarct volume after transient focal ischemia. Brain Res. 1056: 158-167

Bühnemann C, Scholz A, Bernreuther C, Malik CY, Braun H, Schachner M, Reymann KG, Dihné M. (2006) Neuronal differentiation of transplanted embryonic stem cell-derived precursors in stroke lesions of adult rats. Brain (in press)