Article Text

ANTENATAL BACTERIAL ENDOTOXIN (LIPOPOLYSACCHARIDE) POTENTIATES DOPAMINE NEURON LOSS IN ANIMALS EXPOSED TO POSTNATAL EXCITOTOXICITY
  1. J Kassem1,
  2. G Favrais1,2,
  3. S Chalon1,
  4. E Saliba1
  1. 1INSERM U930, University Francois Rabelais, CHRU, Tours, France,
  2. 2INSERM U676, Paris, France

Abstract

Maternal–fetal inflammation and postnatal ischaemia play an important role in the pathogenesis of white matter damage (WMD). These insults are also able to damage developing neurons.

Objective: To evaluate the combined effects of prenatal lipopolysaccharide and postnatal ibotenate, a glutamate analogue, on dopamine neurons and levels.

Methods: Pregnant rats were injected intraperitoneally with either lipopolysaccharide or saline (controls) at days 19 and 20 of gestation. Neonates were given intracerebral injections of ibotenate at P4 and killed at P9. Lesion size was measured after cresyl violet staining. Microglial activation was investigated by immunohistochemistry. Dopamine cell counts were assessed in the striatum and the prefrontal cortex using autoradiography by means of [(3H)] SCH 23390 and [(3H)] YM-09151-2 for D1 and D2 receptors, respectively. Tyrosine hydroxylase immunoreactivity (THir) was used in the mesencephalon as a dopamine neuron marker. Dopamine level was measured using high-performance liquid chromatography.

Results: We observed a significant increase in the lesion size and in microglial activation in lipopolysaccharide groups compared with controls in the cortex and the white matter. Prenatal lipopolysaccharide exposure significantly reduced striatal and cortical D2 receptors (striatum D2 (12%); cortical D2 (16%) p<0.01 as well as THir cells in the substantia nigra (14%; p<0.05). Dopamine levels were significantly increased by lipopolysaccharide exposure (20%; p<0.05)

Conclusion: These findings show that neuronal loss accompanies perinatal WMD and support the view that some dysfunctions seen in preterm infants reflect reduced connectivity between areas of the brain needed for integrating information.

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