Alpha lipoic acid ameliorates detrimental effects of maternal lipopolysaccharides exposure on prefrontal white matter in adult male offspring rats.

BACKGROUND: Activation of the maternal immune system by lipopolysaccharide (LPS) increases the production of proinflammatory cytokines, free radicals, and reactive oxygen species (ROS), all of which play a significant role in the pathogenesis of many offspring neurodevelopmental disorders. Alpha Lipoic Acid (ALA) is a natural compound that has anti-inflammatory and antioxidant properties. This study was performed to assess the effect of prenatal exposure to LPS on the prefrontal white matter of rat offspring and evaluate the potential protective effects of ALA co-administration during pregnancy. METHODS: Pregnant Wistar rats were randomly divided into six groups (n = 6 each group): (1) control, (2) received LPS (100 µg/kg, intraperitoneally (IP) on gestational day 9.5 (GD 9.5), (3) received ALA (20 mg/kg) from GD1 to GD11, (4) LPS+ALA received LPS on GD9.5 and ALA from GD1 to GD11, (5 and 6) received LPS and ALA vehicle respectively. In each group, 21-day old male offspring (2 male pups from each mother) was harvested, and then their prefrontal white matter was separated and prepared for the ultrastructural, stereological, and molecular assays. RESULTS: In utero exposure to LPS led to a significant decrease in nerve cell counts, ultrastructural alterations in myelinated axons, and abnormal changes in genes expression of Sox10,Olig1,yrf,Wnt in the prefrontal of the rat offspring. Co-administration of ALA resulted in amelioration of those abnormal changes in the LPS rat offspring. CONCLUSION: The findings of our preclinical study, explore that prenatal ALA treatment efficiently protects the nervous system against LPS induced abnormal changes in the offspring.

Alterations of neuroimmune cell density and pro-inflammatory cytokines in response to thimerosal in prefrontal lobe of male rats.

Evidence suggests that the effect of heavy metals on neuroimmune cells lead to neurogenic inflammatory responses. In this study, immune cells [mast cells (MCs) and microglia] and pro-neuroinflammation cytokines (interleukin-1b and tumor necrosis factor-α) were assessed in the prefrontal lobe of rat brains exposed to thimerosal in different timeframes. A total of 108 neonatal Wistar rats were divided into three groups having three subgroups. The experimental groups received a single dose of thimerosal (300 µg/kg) postnatally at 7, 9, 11, and 15 days. The vehicle groups received similar injections of phosphate-buffered saline in a similar manner. The control groups received nothing. Samples of the prefrontal cortex were collected and prepared for stereological, immunohistochemical, and molecular studies at timeframes of 12 or 48 h (acute phase) and 8 days (subchronic phase) after the last injection. The average density of the microglia and MCs increased significantly in the experimental groups. This increase was more evident in the 48 h group. At 8 days after the last injection, there was a significant decrease in the density of the MCs compared to the 12 and 48 h groups. Alterations in pro-inflammatory cytokines were significant for all timeframes. This increase was more evident in the 48 h group after the last injection. There was a significant decrease in both neuroinflammatory cytokines at 8 days after the last injection. It was found that ethylmercury caused abnormal neurogenic inflammatory reactions and alterations in the neuroimmune cells that remained for a longer period in the brain than in the blood.

The healing effect of unrestricted somatic stem cells loaded in collagen-modified nanofibrous PHBV scaffold on full-thickness skin defects.

Unrestricted somatic stem cells (USSCs) loaded in nanofibrous PHBV scaffold can be used for skin regeneration when grafted into full-thickness skin defects of rats. Nanofibrous PHBV scaffolds were designed using electrospinning method and then, modified with the immobilized collagen via the plasma method. Afterward, the scaffolds were evaluated using scanning electron microscopy, physical and mechanical assays. In this study; nanofibrous PHBV scaffolds loaded with and without USSCs were grafted into the skin defects. The wounds were subsequently investigated at 21 days after grafting. Results of mechanical and physical analyses showed good resilience and compliance to movement as a skin graft. In animal models; all study groups excluding the control group exhibited the most pronounced effect on wound closure, with the statistically significant improvement in wound healing being seen on post-operative Day 21. Histological and immunostaining examinations of healed wounds from all groups, especially the groups treated with stem cells, showed a thin epidermis plus recovered skin appendages in the dermal layer. Thus, the graft of collagen-coated nanofibrous PHBV scaffold loaded with USSC showed better results during the healing process of skin defects in rat model.

Maternal tamoxifen treatment alters oocyte differentiation in the neonatal mice: inhibition of oocyte development and decreased folliculogenesis.

AIM: Primary germ cells after migration to the developing ovary differentiate to oogonia and oocytes. The formation and number of primordial follicles in early fetal life are determining factors in the fertility state of adult life. Tamoxifen is used both to stimulate ovulation and as an anticancer drug. The aim of the present study was to evaluate the effect of tamoxifen on oocyte and follicular development and differentiation in mice. METHODS: Thirty adult female and 15 adult male mice were used in the present study. The female mice were divided into two groups: control and experimental. Two female mice at their sterous cycle were placed with one male mouse in a cage for mating. The observation of a vaginal plug was considered the 1st day of pregnancy. On the 13th day of pregnancy the mice received 100 microg tamoxifen by i.p. injection. At the end of pregnancy 2-, 3-, 6- and 7-day-old newborns were killed and their ovaries were fixed and prepared for light and electron microscopic studies. The number of follicular nests and diameter of primordial and primary follicles were determined using Motic software (Motic Incorporation Ltd, Canada) and compared with control values using t-test. RESULTS: Microscopy and morphometry showed that oocyte nests are formed on the 2nd and 3rd days and follicles are distinguished on the 6th and 7th days. Morphometric studies revealed that the number and diameters of oocyte nests were significantly (P < 0.001) reduced in the experimental groups compared to the control group. However, the numbers and diameters of primordial and primary follicles in experiential and controls were not significantly different. Electron microscopic studies revealed that in the control group, oocytes were separated from each other and were at primordial follicle stage. However, in the experimental group, the oocytes were in clusters as oocyte nests. CONCLUSION: The results indicate that tamoxifen suppresses follicular differentiation at early stages but does not affect the development of already differentiated follicles.