Time-dependent effect of in utero inflammation: a longitudinal study in rats.

Abstract

OBJECTIVE: To determine the impact of the duration of fetal exposure to inflammation on the neurological outcome of pups. METHOD: Time-pregnant Sprague-Dawley rats (n = 32) received intraperitoneal injection of lipopolysaccharides (LPS; 500 &#xb5;g/kg), or an equivalent volume of vehicle 3, 6, 12 and 24 h before C-section. Maternal serum and amniotic fluid were tested for cytokines. Motor activity of resuscitated pups (n = 58) was analyzed using the open-field test (20 d). Brains were collected for histopathological examination. RESULTS: Perinatal mortality increased with the duration of fetal exposure to LPS. All parameters tested with the open-field test were lower in the LPS 12 h exposure group compared to the control group (p < 0.05). Tissue inhibitor of metalloproteinase 1 (TIMP-1) was statistically increased in maternal blood after 3, 6 and 12 h of LPS injection (p < 0.05 versus control). CONCLUSION: A threshold of duration of exposure to inflammation is demonstrated, before which delivery should be performed in order to prevent brain damage.