The phosphodiesterase-4 inhibitor Rolipram promotes cognitive function recovery in prenatal Escherichia coli infected offspring

Objective: Preterm infants are especially vulnerable to intrauterine infection-induced brain injury, which is closely relevant with cognitive deficits and cerebral palsy. Rolipram, a phosphodiesterase-4 inhibitor, can improve cognition in rodents. However, the underlying roles and mechanisms are not well investigated. Methods: In the present study, we used intrauterine Escherichia coli (E. coli) infected model. Escherichia coli was inoculated into pregnant rats' uterine cervix at embryonic day 15 (E15) while the control group was given normal saline. Rolipram was administered by intraperitoneal (i.p.) injection once daily from postnatal day (P) 1-7. Morris water maze test was used for cognitive behavior test. Hippocampal neural stem/precursor cells (NSPCs) proliferation and neuronal differentiation were studied by immunofluorescent staining. The expressions of p-CREB, p-Akt, TrkB and BDNF were estimated by western-blot analysis. Results: The data showed that Rolipram could ameliorate cognitive deficits and enhance NSPCs proliferation and neuronal differentiation in intrauterine infected offspring. Additionally, Rolipram could significantly increase p-CREB/CREB, p-Akt/Akt, TrkB and BDNF levels. Conclusions: These results suggested that Rolipram might play a neuroprotective role to promote cognitive function recovery after intrauterine infection. And hippocampal NSPCs proliferation and neuronal differentiation might be enhanced via CREB/Akt/BDNF signal transduction.