Artikel
Cellular strategies after experimental traumatic brain injury. A histochemical analysis of the therapeutic effects of cell transplantation on brain tissue
Zelluläre Strategien nach experimentellem Schädel-Hirn-Trauma. Eine histochemische Analyse der therapeutischen Effekte einer Zelltransplantation auf das Hirngewebe
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Autoren
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M. Skardelly
- Klinik für Neurochirurgie, Universitätsklinikum Leipzig
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S. Burdack
- Klinik für Neurochirurgie, Universitätsklinikum Leipzig
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K. Gaber
- Klinik für Neurochirurgie, Universitätsklinikum Leipzig
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J. Hermann
- Klinik für Neurochirurgie, Universitätsklinikum Leipzig
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M. U. Schuhmann
- Klinik für Neurochirurgie, Universitätsklinikum Leipzig
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J. Meixensberger
- Klinik für Neurochirurgie, Universitätsklinikum Leipzig
| Veröffentlicht: | 30. Mai 2008 |
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Gliederung
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Objective: Cell transplantation as a cellular strategy to improve clinical outcome has proven to be efficient in animal models of a variety of acute and chronic diseases of the nervous system. Unfortunately the underlying alleviating mechanisms are still elusive since in most cases it could not be shown that cell replacement plays a mayor role. This study investigates the effect of transplantation (Tx) of differentiated human fetal neuronal progenitor cells on alterations of the brain tissue following traumatic brain injury (TBI) in the rat.
Methods: TBI was caused by the Controlled Cortical Impact model to 72 male SD rats. Rats received either no cells, or a stereotactic intracerebral (~1x105 cells) or intravenous (~5x105 cells) transplantation of fluorescence dye-labeled differentiated human fetal neuronal progenitor cells 24h after TBI. Histochemical localization of the graft and analysis of the neuronal, astroglial, microglial and vascular compartments was conducted and associated with neurological outcome and MRI results.
Results: Brain injured animals, who received either intracerebral stereotactic or intravenous injection of fluorescence-labeled differentiated human fetal neural stem cells showed better neuronal survival in the penumbra zone after 12 weeks (Tx/control: local 142% and systemic 151%, p<0,05), a decreased astrogliosis, an elevation of RECA (Rat Endothelial Cell Antigen) as a surrogate of the perfusion during the first 4 weeks but also an elevation of the microglial reaction. Tx cells were found in the putamen migrating along the white matter after local Tx but could never be found after systemic Tx.
Conclusions: Our histological results in conjunction with the already presented functional and MRI results suggest that the better performance and the smaller brain defects of both transplanted groups are probably not due to cell replacement but due to 1. a transient increase of the local perfusion and likely to other neuroprotective and regenerative mechanisms 2. a higher neuronal survival in the penumbra and 3. a smaller glial scar formation.
