Prenatal Exposure to Diethylhexyl Phthalate Impairs the Recovery of Spatial Memory Post-traumatic Brain Injury in a Sex-specific Manner

Background Diethyl hexyl phthalate (DEHP) is a chemical plasticizer that causes significant neurological impairments after prenatal exposure. The impact of these exposures on cognitive recovery after severe traumatic brain injury (sTBI) has never been studied. We hypothesized that prenatal exposure to DEHP will impair cognitive recovery after a sTBI in a sex-specific manner. Methods To test this hypothesis, six-month-old male and female offspring that were prenatally exposed to DEHP were subjected to controlled cortical impact injuries, and their spatial memory was tested weekly using a Morris Water Maze (MWM) test for 4 weeks post-sTBI. Results We observed that DEHP-exposed male rats demonstrated significantly impaired spatial memory up to four weeks post-sTBI when compared to controls. In contrast, DEHP-exposed female rats showed no detectable impairment in spatial memory recovery compared to injured controls. These observations were accompanied by marked increases in neurotransmitter levels in the cortex and dopamine levels in the hippocampus of female, but not in male rats. No significant differences in lesion area and number of hippocampal neurons were observed in both sexes. Conclusion These results suggest that prenatal exposure to DEHP may have long lasting effects in the brain that could lead to impaired recovery specifically in male subjects following post-sTBI.