A critical postnatal period of heightened vulnerability to lipopolysaccharide.
Evidence of respiratory abnormalities and vulnerability to infection during a critical period of development have been implicated in Sudden Infant Death Syndrome (SIDS). Here we investigated whether the acute hypoxic ventilatory response (HVR) exhibits a heightened vulnerability to the endotoxin lipopolysaccharide (LPS) during a critical period of development. The acute HVR was measured 2h after an i.p. injection of saline or LPS (0.1mg/kg) at various postnatal (P) ages (P5, P10, or P20days). LPS attenuated the early (1-2min) and late (4-6min) phase of the acute HVR in P10 but not P5 or P20 rats. The P10 age group exhibited the largest increase in brainstem TNFα and iNOS mRNA expression following LPS. LPS also caused a higher mortality rate in P10 rats (48%) compared to P5 (12%) and P20 (0%) age groups. After stratifying LPS treated P10 rats into survivors vs non-survivors, only the latter exhibited an attenuated HVR (specifically the early phase). Thus, the heightened vulnerability to endotoxin exposure during this critical period of development is characterized by a depression of the ventilatory response to acute hypoxia in association with an increased incidence of mortality. These data share similarities with some of the circumstances surrounding a SIDS scenario, including evidence of infection, increased brainstem cytokine expression, a disturbance in respiratory control, and a peak incidence of mortality during a critical period of development.
Department of Pediatrics, Case Western Reserve University, Rainbow Babies & Children's Hospital, Cleveland, OH, 44106, USA.
Kyle S
KS
Rourke
Department of Pediatrics, Case Western Reserve University, Rainbow Babies & Children's Hospital, Cleveland, OH, 44106, USA.
Catherine A
CA
Mayer
Department of Pediatrics, Case Western Reserve University, Rainbow Babies & Children's Hospital, Cleveland, OH, 44106, USA. Electronic address: pmm71@case.edu.
Peter M
PM
MacFarlane
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006935:Hypercapnia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010991:Plethysmography; D012123:Pulmonary Ventilation / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013990:Tidal Volume / Q000187:drug effects; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D008070:Lipopolysaccharides; D012333:RNA, Messenger; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II
Breathing; Critical period; Development; Inflammation; SIDS