Hyperoxia-induced lung injury plays a key role in the development of bronchopulmonary dysplasia (BPD), characterized by inflammatory injury and impaired lung development in preterm infants. Although BPD is a predictor of poor neurodevelopmental outcomes, currently it is uncertain how lung injury contributes to brain injury in preterm infants. Extracellular vesicles (EVs) are a heterogeneous group of cell-derived membranous structures that regulate intercellular and inter-organ communications. Gasdermin D (GSDMD) has emerged as a key executor of inflammasome-mediated cell death and inflammation. In this study, we utilized a neonatal rat model of BPD to assess if hyperoxia stimulates lung release of circulating EVs and if these EVs induce lung and brain injury. We found that hyperoxia-exposed rats had elevated numbers of plasma-derived EVs compared to rats maintained in room air. These EVs also had increased cargos of surfactant protein C, a marker of type II alveolar epithelial cells (AEC), and the active (p30) form of GSDMD. When these EVs were adoptively transferred into normal newborn rats via intravenous injection, they were taken up both by lung and brain tissues. Moreover, EVs from hyperoxic animals induced not only the pathological hallmarks of BPD, but also brain inflammatory injury in recipient rats, as well as inducing cell death in cultured pulmonary vascular endothelial cells and neural stem cells (NSC). Similarly, hyperoxia-exposed cultured AEC-like cells released EVs that also contained increased GSDMD-p30 and these EVs induced pyroptotic cell death in NSC. Overall, these data indicate that hyperoxia-activated circulating EVs mediate a lung to brain crosstalk resulting in brain injury and suggest a mechanism that links lung injury and neurodevelopmental impairment in BPD infants.

Purpose and background: the aim of this study was investigating intraperitoneal injection of different doses of Imipramine on the number of follicles in the adult female rat. Infertility that occurs as a result of taking drugs is an important clinical issue. Rate of infertility that has been reported as a result of taking antidepressant drugs is 60%, in spite of its popularity a slight amount of studies has been formed to clarify the mechanism of action on these drugs, this study has written about Imipramine. forty female wistar 180 ± 20 g, selected and distributed them into groups experimental 1, 2, and 3. And they injected 6.25, 12.5, and 25 mg/kg bodyweight Imipramine respectively for 4 weeks, control group receives nothing, and sham group receives distilled water, at the end the samples of ovary tissue were taken to the laboratory for slice preparation, and slides of different parts of ovary made us available to count total number of follicles in each ovary. Results showed that this drug has no effect on bodyweight, ovary and primitive, secondary, graffian and atretic follicles. Different doses of imipramine, number of primary follicles, also 25 mg/kg dose of this drug has caused Corpusluteum to decrease.

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