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

Abstract EN

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.