The effects of maternal diet on the neuroimmune responses of the offspring remain to be elucidated. We investigated the impact of maternal ketogenic diet (KD) on the NLRP3 inflammasome response in the offspring’s brain. C57BL/6 female mice were randomly allocated into standard diet (SD) and ketogenic diet (KD) groups for 30 days. After mating, the presence of sperm in the vaginal smear was considered day 0 of pregnancy, and female mice continued their respective diets during pregnancy and the lactation period. Following birth, pups were further allocated into two groups and given either LPS or intraperitoneal saline on postnatal (PN) days 4, 5 and 6; they were sacrificed on PN11 or PN21. Neuronal densities were significantly lower globally in the KD group when compared to the SD group at PN11. Neuronal density in the prefrontal cortex (PFC) and dentate gyrus (DG) regions were also significantly lower in the KD group when compared to the SD group at PN21. Following administration of LPS, the decrease in the neuronal count was more prominent in the SD group when compared to the KD group in the PFC and DG regions at PN11 and PN21. NLRP3 and IL-1β were higher in the KD group than in the SD group at PN21 in the PFC, CA1 and DG regions, and were significantly lower in the DG region of the KD group especially when compared to the SD group following LPS. Results of our study reveal that maternal KD negatively affects the offspring’s brain in the mouse model. The effects of KD exhibited regional variations. On the other hand, in the presence of KD exposure, NLRP3 expression after LPS injection was lower in the DG and CA1 areas but not in the PFC when compared to SD group. Further experimental and clinical studies are warranted to elucidate the molecular mechanisms underlying the impact of antenatal KD exposure and regional discrepancies on the developing brain.

Although closure of ductus arteriosus requires multiple intriguing cell signalling pathways, current treatment options merely act through cyclooxygenase inhibition. Expectedly, medical management of ductus arteriosus is quite far away from optimum and there is an ongoing debate on its efficiency and safety. The ideal therapeutic agent for patent ductus arteriosus should target vascular remodelling and support the arrested molecular steps that should completely eventuate during anatomical closure.Platelet-rich plasma injection, which has been used as a treatment alternative for many musculoskeletal conditions, can be a promising solution in this context by compensating the relative platelet dysfunction in preterms and providing a convenient microenvironment for proper cellular communication for ductal closure.First, by inducing hyaluronan synthase, platelet-rich plasma can induce mount formation in the intima, which is the significant defective milestone in preterms. Second, by providing platelet-derived growth factor, it can further stimulate platelet agregation and occlusion of the lumen. Finally, it can provide an increment in local vascular endothelial growth factor and transforming growth factor-β levels, which cannot be achieved because of insufficient intramural hypoxia. Migration of the vascular smooth muscles would further be triggered by transforming growth factor-β and vascular endothelial growth factor, aiding a major contribution to ductal closure.Above and beyond all other considerations, opportunity of local application would render maximum effectiveness and minimum side effects.

The crucial role of platelets in the permanent closure of the ductus arteriosus has recently been elucidated in an animal model; however, clinical studies investigating the impact of platelet count on ductal patency have conflicting results. Our aim is to compare platelet count, indices and serum platelet-derived growth factor levels in preterms with and without ductal patency. Preterms with a gestational age of 27-30 weeks followed up during a twelve-month period in the neonatal intensive care unit of Adnan Menderes University Hospital were enrolled. Infants underwent echocardiographic evaluation starting on the second day and subsequently assessed every other day until ductal closure was achieved, or upon clinical signs of reopening. Platelet-derived growth factor was measured on the second and fifth days of life. Eleven very low birth weight infants who subsequently required medical treatment for patent ductus arteriosus were compared with twenty-three infants with closed ductus. Although platelet count and indices were similar, median serum plateletderived growth factor levels on day 5 were significantly lower among babies who subsequently required medical treatment for ductal patency (874.6 vs 1099.6 pg/ml). The current study points out a possible association between serum platelet-derived growth factor levels and ductal closure. Our results suggest that platelet-derived growth factor may play a role in ductal closure independent from platelet count and might be used as an adjunct surrogate for prediction of future need for treatment for hemodynamically significant patent ductus arteriosus in preterm infants.