The risk of significant cardiorespiratory challenges increases with decreasing gestational age at the time of birth. Many infants less than 32 weeks of gestational age will require respiratory support in the form of supplemental oxygen to offset cardiorespiratory instability that commonly leads to hypoxia. The vulnerability of the population due to their limited metabolic reserves and their immaturity means preterm infants often need on-going access to specialist clinical care requiring prolonged hospital stays. Exposure to pathogens within the hospital increases the risk of nosocomial infection. Hypoxia and inflammation have been reported to disrupt the blood-brain-barrier, which may lead to microglia activation.
The aim of our study was to assess if the BBB within the paraventricular nucleus was compromised in neonatal rats exposed chronic intermittent hypoxia/hyperoxia and acute S. Aureus derived lipoteichoic acid and peptidoglycan (LTA&PGN). In this model we have previously demonstrated an increase in circulating cytokines, cortisol and progesterone in response to bacterial derived products.
Methods: Female dams and their litters (male and female) were either left at normoxia or placed in an environmental chamber and FiO2 was manipulated to generate a pattern of intermittent hypoxia (8%)/hyperoxia(30%)/normoxia(21%) (CIHH) between postnatal day (PND) 3 and 12. On PND13 the pups from both groups were divided between saline-treatment and LTA&PGN (i.p) treatment. Ultrasonic vocalisation was measured 3 hours after treatment on PND13 and animals were later euthanised with pentobarbital and perfused with FITC-dextran. Ultrasonic vocalisations were recorded using ultravox and analysed using Deepsqueak (n=5-10). The brains were post-fixed in 10% formalin, cryoprotected with 20% sucrose and cryosectioned using Lecia cryostat. Images were visualised using confocal microscopy at 50um. Analysis was performed by sampling extra/intra ratio of fluorescence of capillaries (n=5-6).
Results: The number and frequency of calls were not different between experimental groups. When male and female animals were exposed to LTA&PGN the extra/intra ratio of floresence of capillaries increased in the magnocellular and the intermediocellular region of the PVN (three-way ANOVA, Gas x LTA&PGN p=0.02 and p=0.01 respectively. Conclusion: There is no evidence of a change in vocalisation when pups are temporarily separated from their dam despite exposure to early life stress. There is some evidence of increased leakiness in pups exposed to S. Aureus derived LTA&PGN, whereas when rat pups are exposed to CIHH and LTA&PGN the extra/intra ratio of fluorescence is no longer different.