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Details van artikel 23 van 37 gevonden artikelen
| Titel: |
Modeling Pediatric Head Trauma: Mechanisms of Degeneration and Potential Strategies for Neuroprotection |
| Auteur: |
Petra Bittigau Daniela Pohl Marco Sifringer Hiroki Shimizu Masuhiro Ikeda Masahiko Ishimaru Daniel Stadthaus Susanne Fuhr Krikor Dikranian John W. Olney Chrysanthy Ikonomidou |
| Verschenen in: |
Restorative neurology and neuroscience |
| Paginering: | Jaargang 13 (2003) nr. 1-2 pagina's 11-23 |
| Jaar: |
2003-04-03 |
| Inhoud: |
We have developed a model for head trauma in infant rats in an attempt to study mechanisms of neurodegeneration in the developing brain and were able to morphologically characterize two distinct types of brain damage. The first type or primary damage evolved within 4 hrs after trauma and occurred by an excitotoxic mechanism. The second type or secondary damage evolved within 6-24 hrs and occured by an apoptotic mechanism. Primary damage remained localized to the parietal cortex at the site of impact. Secondary damage affected distant sites such as the cingulate/retrosplenial cortex, subiculum, frontal cortex, thalamus, hippocampal dentate gyrus and striatum. Histological evidence of delayed cell death was preceded by decrease of bcl-2- in conjunction with increase of c-jun-mRNA-levels, already evident at 1 hr after trauma. Increase of CPP32-like activity and elevated concentrations of oligonucleosomes in affected brain regions represented additional findings to indicate that this secondary disseminated degenerative reaction is apoptotic in nature. At the age of 7 days, secondary apoptotic damage was more severe than primary excitotoxic damage, but its severity declined with increasing age. In 7-days-old rats, NMDA antagonists protected against primary excitotoxic damage but increased severity of secondary apoptotic damage whereas the free radical scavenger SPBN, the tumor necrosis factor (TNF) inhibitor pentoxifylline and the antioxidant N-acetylcystein mitigated apoptotic damage. These findings demonstrate that in the developing rat brain apoptosis and not excitotoxicity determines neuropathologic outcome following head trauma. Whereas radical scavengers and TNF-inhibitors may prove useful in treatment of pediatric head trauma, great caution should be applied in regards to the use of NMDA antagonists because of the inherent risk of apoptosis promotion. |
| Uitgever: |
IOS Press |
| Bronbestand: |
Elektronische Wetenschappelijke Tijdschriften |
Details van artikel 23 van 37 gevonden artikelen
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