Postnatal development of lipopolysaccharide-induced inflammatory response in the brain.
OBJECTIVE
This study aimed to characterize postnatal development of lipopolysaccharide (LPS)-induced inflammatory response in the brain.


METHODS
Postnatal day (P)1, P21 and P70 Sprague-Dawley(®) rats were treated with saline or 0.25 mg/kg LPS for 2 h, and the mRNA expression of neuroinflammatory mediators in the brain was determined using reverse transcriptase-polymerase chain reaction (RT-PCR). The kinetics of LPS-induced neuroinflammatory mediators in the brain of P1 and P21 animals was determined using RT-PCR, and the kinetics of LPS-induced cytokines in the serum were determined using ELISA. The basal levels of Toll-like receptor (TLR)-4, CD14, and myeloid differentiation factor 88 (Myd88) were measured at the mRNA and protein levels using RT-PCR and Western blot assay respectively.


RESULTS
The mRNA expression levels of cytokines and chemokines were considerably increased in P21 and P70 brains but not significantly altered in P1 brain at 2 h following LPS stimulation. Instead, the induction of cytokines and chemokines was significantly delayed in the brain of P1 animals following LPS stimulation, which was associated with diminished Myd88 production in P1 brain. In parallel, the cytokine response in the serum of P1 animals after LPS stimulation was also delayed compared to P21 animals.


CONCLUSIONS
TLR-4-mediated innate immunity in the brain was significantly delayed in P1 animals, and underwent significant development during the early postnatal period.
Ortega
Andres
A
Department of Biological Sciences, Seton Hall University, 400 South Orange Avenue, South Orange, NJ 07079, USA.
Jadeja
Viren
V
Zhou
Heping
H
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004660:Encephalitis / Q000276:immunology* / Q000473:pathology; D005260:Female; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology*; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology
D018925:Chemokines; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051197:Toll-Like Receptor 4