Induction of proinflammatory cytokines has been proposed to be a link between prenatal maternal intrauterine infection and neonatal brain damage. It is known that the endotoxin, lipopolysaccharide (LPS), released during bacterial infection crosses the placenta. Cytokine induction in the fetal rat brain after maternal administration of LPS was determined by reverse transcriptase-polymerase chain reaction method. LPS suspension in pyrogen-free saline was administered (i.p.) to pregnant rats at 18 d of gestation. The control group was treated with pyrogen-free saline. Expression of the proinflammatory cytokines, tumor necrosis factor-α and IL 1-β mRNA, in the fetal rat brain was increased in a dose-dependent manner at 1 h after LPS administration. The great increase in expression of IL-1β mRNA was only observed at 1 h after injection of LPS (4 mg/kg), whereas the increased expression of tumor necrosis factor-α was still detectable from 4 to 24 h after LPS administration. Brain injuries were examined by immunohistochemistry in 8-d-old rat pups born to the dams that were consecutively treated with LPS (500 μg/kg) or pyrogen-free saline on gestation d 18 and 19. No apparent necrotic tissue damage was found in either the LPS group or the control group. Myelin basic protein staining, as a marker of myelin, was clearly observed in the internal capsule and the fimbria hippocampus in the rat brain from the control group. Myelin basic protein staining was much less and weaker in the brains of the LPS-treated group. Glial fibrillary acidic protein–positive astrocytes were observed in both the control and the LPS-treated groups. The LPS-treated group appeared to have more glial fibrillary acidic protein–positive astrocytes in the hippocampal and the cortex areas of the brain than the control group. Immunoblotting data showed that glial fibrillary acidic protein content in the cortex or the hippocampus of the LPS-treated rat brain was higher than in the control group. OX-42–positive staining (a marker of the type 3 complement receptors) of microglial cells was greatly reduced in the 8-d-old rat brain after maternal LPS administration. However, histochemistry with tomato lectin showed that staining of both amoeboid and ramified microglial cells in the LPS-treated rat brain was similar to that in the control group. The overall results indicate that maternal LPS administration induces an increased expression of IL-1β and tumor necrosis factor-α mRNA in the fetal brain. Maternal LPS administration also increases glial fibrillary acidic protein–positive astrocytes, decreases myelin basic protein and alters immunoreactivity of microglia in the brain of offspring. Although results from the current study do not provide direct evidence linking LPS-induced cytokines with the abnormalities in the neonatal rat brain, our animal model may be appropriate for exploring the mechanisms involved in the effects of maternal infection on glial cells in the brains of offspring.

Serotonin (5-HT) plays a key role in early brain development, and manipulation of 5-HT levels during this period can have lasting neurobiological and behavioral consequences. It is unclear how perinatal exposure to drugs, such as selective serotonin reuptake inhibitors (SSRIs), impacts cortical neural network function and what mechanism(s) may elicit the disruption of normal neuronal connections/interactions. In this article, we report on cortical wiring organization after pre- and postnatal exposure to the SSRI citalopram. We show that manipulation of 5-HT during early development in both in vitro and in vivo models disturbs characteristic chemoarchitectural and electrophysiological brain features, including changes in raphe and callosal connections, sensory processing, and myelin sheath formation. Also, drug-exposed rat pups exhibit neophobia and disrupted juvenile play behavior. These findings indicate that 5-HT homeostasis is required for proper brain maturation and that fetal/infant exposure to SSRIs should be examined in humans, particularly those with developmental dysfunction, such as autism.

This study evaluated the effect of exogenous vascular endothelial growth factor (VEGF) on tendon healing and regulation of other growth factors in a rat Achilles tendon model. Fifty Sprague-Dawley rats were used. In the experimental group, the left Achilles tendon was transected and repaired with the modified Kessler suture technique, and the right Achilles tendon was transected and repaired with resection of plantaris tendon. VEGF, 100 μl (50 μg/ml), was injected into each tendon at the repair site. The same surgical procedures were performed in the control group, with the same volume of saline injected into the repair sites. At intervals of 1, 2, and 4 weeks, the animals were killed and the tendons were harvested and evaluated for tensile strength (1, 2, and 4 weeks) and gene expression (postoperative day 4). At 1 week postoperatively, when plantaris tendon was preserved, the tensile strength of the repaired tendons with VEGF treatment (3.63 ± 0.62 MPa) was significantly higher than the tensile strength of the repaired tendons with saline treatment (2.20 ± 0.36 MPa). There was no difference in tensile strength between the two groups without the plantaris tendon support. At 2 weeks postoperatively, the tensile strength was 11.34 ± 3.89 MPa in the group with VEGF treatment and plantaris tendon preservation, which was significantly higher than the tensile strength in the other groups. There was no significant difference in tensile strength among the groups at 4 weeks postoperatively. The gene expression showed that transforming growth factor-β in the VEGF-treated tendon was up-regulated in the early stage of tendon healing, whereas expression of platelet-derived growth factor, basic fibroblast growth factor, and insulin-like growth factor-1 was not significantly different among the groups. In conclusion, administration of exogenous VEGF can significantly improve tensile strength early in the course of the rat Achilles tendon healing and was associated with increased expression of transforming growth factor-β.