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Biomed Res Int. 2015;2015:318306. doi: 10.1155/2015/318306. Epub 2015 Mar 30.

Effects of PMA (PHORBOL-12-MYRISTATE-13-ACETATE) on the Developing Rodent Brain.

Author information

1
Department of Pediatrics I, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.
2
Department of Radiology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.
3
Department of Neonatology, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
4
Department of Anesthesiology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.

Abstract

Perinatal infections have a negative impact on brain development. However, the underlying mechanisms leading to neurological impairment are not completely understood and reliable models of inflammation are urgently needed. Using phorbol-myristate-acetate as an activator of inflammation, we investigated the effect on the developing rodent brain. Neonatal rats and mice deficient in IL-18 or IRAK-4 were exposed to PMA. Brains were assessed for regulation of pro- and anti-inflammatory cytokines and cell death 24 hrs, 7 and 14 days after treatment. PMA induced an inflammatory response and caused widespread neurodegeneration in the brains of 3- and 7-day-old rats. In contrast, 14-day-old rats were resistant to the neurotoxic effect of PMA. Histological evaluation at the age of 14 and 21 days revealed a destruction of the cortical microstructure with decreased numerical density of neuronal cells. Mice deficient in IL-18 or IRAK-4 were protected against PMA induced brain injury. PMA treatment during a vulnerable period can alter brain development. IL-18 and IRAK-4 appear to be important for the development of PMA induced injury.

PMID:
25918710
PMCID:
PMC4396138
DOI:
10.1155/2015/318306
[Indexed for MEDLINE]
Free PMC Article

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