Maternal Exercise before Pregnancy Alleviates Periventricular Leukomalacia by Lipopolysaccharide-Induced Maternal Intrauterine Inflammation in Infant Rat Brain

Abstract

In the present study, we investigated the effects of maternal exercise before pregnancy on lipopolysaccharide (LPS)-induced hypomyelination and astrogliosis in neonatal rats. Female Sprague-Dawley rats (180 ± 10 g, 8 weeks old, n = 45) were used for maternal rats in this experiment. Before pregnancy, rats were randomly divided into three groups: the non-ex-control (CON) group, non-ex-LPS (LPS) group, and the Pre-ex-LPS (Ex-LPS) group (n = 15 in each group). The rats in the Ex-LPS group were forced to run on a motorized treadmill for 30 min once a day for 4 weeks. After the completion of exercise, all rats were allowed to mate with male rats for a period of 24 h. After conforming of pregnancies (n = 5 in each group), the maternal rats were treated with 0.15 mg/kg LPS and/or the same amount of pyrogen-free saline (PFS) on the 15th, 17th, and 20th day of pregnancy. The expression of Cyclooxygenasee-2 (COX-2) and Tumor necrosis factor-α (TNF-α) in brain was analyzed by RT-PCR. Immunohistochemistry for the glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) in the corpus callosum were conducted. In results, the expressions of COX-2, TNF-α and GFAP was significantly increased while the expression of MBP was significantly decreased in the neonatal rat brain of the LPS group compared to those of the CON group (p<.05). This result showed that LPS might induce toxic effect in neonatal rat brain such as hypomyelination and astrogliosis. In contrast, the expressions of COX-2, TNF-α and GFAP was significantly decreased while the expression of MBP was significantly increased in the neonatal rat brain of the Ex-LPS group compared to those of the LPS group (p<.05). In conclusion, the present results revealed that regular maternal exercise before pregnancy might be effective to ameliorate the symptoms of PVL such as astrogliosis and hypomyelination in neonatal rat brain and it can be used as a therapeutic strategy for preventing the detrimental effects of CP.