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Downregulation of amyloid precursor protein (APP) expression following post-traumatic cyclosporin-A administration
Journal article   Peer reviewed

Downregulation of amyloid precursor protein (APP) expression following post-traumatic cyclosporin-A administration

C Van Den Heuvel, James J Donkin, J W Finnie, P C Blumbergs, T Kuchel, B Koszyca, J Manavis, N R Jones, P L Reilly and R Vink
Journal of Neurotrauma, Vol.21(11), pp.1562-1572
2004
DOI: https://doi.org/10.1089/neu.2004.21.1562
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https://doi.org/10.1089/neu.2004.21.1562View
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Abstract

amyloid precursor protein cyclosporin-A head injury model immunocytochemistry RTPCR sheep traumatic brain injury
The aim of these studies was to assess and quantitate the effects of cyclosporin-A (CyA) on brain APP messenger RNA and neuronal perikaryal APP antigen expression following controlled focal head impact in sheep. Impact results in a significant increase in both APP mRNA and neuronal perikaryal APP antigen expression. Post-traumatic administration of CyA (intrathecal 10 mg/kg) resulted in a reduction in APP mRNA and neuronal perikaryal antigen expression. At 2 h postinjury, CyA treatment caused a statistically significant (p < 0.05) 1.3±0.1-fold decrease in APP mRNA in the central gray matter of impacted sheep compared to untreated impacted sheep. A more profound reduction in APP mRNA synthesis (1.6±0.2 fold) was evident at 6 h (p < 0.05). The mean percentage brain area with APP immunoreactive neuronal perikarya at 6 h post-injury was 94.5% in untreated impacted animals, 10.0% in CyA-treated impacted animals, 5.5% in untreated non-impacted animals, and 6% in CyA-treated non-impacted controls. These results demonstrate that CyA has a downregulatory effect on increased APP expression caused by TBI.

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