Endotoxin-induced cerebral pathophysiology: differences between fetus and newborn

Area of Science:

• Perinatal Medicine
• Neuroscience
• Immunology

Background:

• The comparative pathophysiology of perinatal infection in fetuses and newborns remains unclear.
• Endotoxemia can affect brain function and integrity in developing mammals.

Purpose of the Study:

• To contrast the cerebral effects of bacterial endotoxin (lipopolysaccharide, LPS) in fetal sheep and newborn lambs.
• To investigate differences in cerebro-vascular function, inflammatory responses, and brain injury between fetal and neonatal endotoxemia.

Main Methods:

• Fetal sheep and newborn lambs were administered intravenous LPS or saline over three consecutive days.
• Cerebral blood flow (CBF) and cerebral vascular resistance (CVR) were monitored for 12 hours daily.
• Plasma TNF-alpha, nitrate/nitrite concentrations, and macrophage infiltration in the caudate nucleus (CN) and periventricular white matter (PVWM) were quantified.

Main Results:

• Both fetuses and newborns exhibited acute cerebral vasoconstriction within 1 hour of LPS injection.
• Fetuses experienced prolonged cerebral vasodilatation and doubled plasma nitrate/nitrite concentrations, unlike newborns.
• Fetal brains showed 2-3 times greater infiltration of activated macrophages in the CN and PVWM compared to newborns.

Conclusions:

• Fetuses and newborns share an acute disruption of cerebral circulation following LPS exposure.
• Fetuses exhibit a more prolonged circulatory disruption, increased inflammatory cell infiltration, and heightened susceptibility to brain injury compared to newborns.