Of note, IL-6 was significantly increased by Pam3CSK4 but not by LPS. TNF-a levels did not change in either of the two treatment groups. IL-10 and IL-17 levels were below the limits of detection in all brain homogenate samples tested. To further examine the inflammatory LY 266097 hydrochloride response, we stained brain sections for the microglia marker Iba-1. There was a significant increase of Iba-1 positive cells in the Pam3CSK4- treated group compared with endotoxin-free saline treated animals, while there was no difference between the LPS-treated group and endotoxin-free saline group. In the present study, we found that repeated JWH 018 systemic administration of a TLR2 agonist induced elevated cytokine/ chemokine levels in brain homogenates, reduced neonatal gray and white matter volume and hippocampal neuron density, and increased number of microglia cells. By adulthood, brain injury had recovered and there was no detectable long-term change in memory function. To our knowledge, this is the first report of the role of TLR2 agonists on short and long term neonatal brain development. The present study provides important direct evidence that systemic inflammation via TLR2 may exert negative effects on neonatal brain development. In the rodent, there is a major growth spurt of the brain in the first postnatal week, which equates to the second-third trimester in human pregnancy, a developmental window when white matter damage or deficiency of white matter growth is presumed to occur in the human. We used a repeated Pam3CSK4 exposure model from PND3 up to PND11, therefore, covering the period of rapid brain growth in rodents. To ensure a biologic effect, we used a relatively high dose of Pam3CSK4 compared with other in vivo studies in the adult, that range from 5 mg/kg to 2 mg/kg. However, 5 mg/kg Pam3CSK4 and 0.3 mg/kg LPS treatment produced almost identical levels of KC and MCP-1 in brain homogenates, and despite this relatively high dose, we found no mortality or other signs of morbidity. Similarly, in previous studies we found no adverse effects using the same dose of the TLR2 agonist Lipoteichoic acid. These observations suggest that TLR2 agonists have relatively lower potency in neonatal mice compared with the TLR4 agonist LPS. TLR2 mRNA and protein is expressed in the cortex in embryonic and early postnatal stages of development, with relatively low expression before birth that increases during the first 2 weeks of life. Loss of TLR2 does not appear to result in direct defects in cerebral development.