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

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.
Authors	Mark Dzietko, Maria Hahnemann, Oliver Polley, Marco Sifringer, Ursula Felderhoff-Mueser, Christoph Bührer
Journal	BioMed research international (Biomed Res Int) Vol. 2015 Pg. 318306 ( 2015) ISSN: 2314-6141 [Electronic] United States
PMID	25918710 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Interleukin-18 Phorbol Esters phorbol-12-myristate Interleukin-1 Receptor-Associated Kinases Irak4 protein, mouse
Topics	Animals Brain (drug effects, growth & development) Brain Injuries (chemically induced, genetics, physiopathology) Female Inflammation (chemically induced, metabolism, physiopathology) Interleukin-1 Receptor-Associated Kinases (deficiency, genetics) Interleukin-18 (deficiency, genetics) Mice Phorbol Esters (toxicity) Pregnancy Rats

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