Pentylenetetrazole (PTZ)-induced kindling is an animal model for studying human temporal lobe epilepsy (TLE), which is characterized by alterations of hippocampal neurons and memory. Although the intranasal (IN) administration of oxytocin (OT) has limited efficiency, nanoparticles (NPs) are a promising candidate to deliver OT to the brain. However, there are very limited data on epilepsy research about oxytocin-loaded nanoparticles (NP-OTs). The aim of this study is to investigate the effects of IN administration of chronic NP-OTs on the hippocampus of PTZ-induced male epileptic rats in terms of seizure severity, memory, neurogenesis, and neuronal damage. Saline/OT/NP-OTs were administrated to both control (Ctrl) and PTZ groups intranasally. Consequently, saline and PTZ were injected, respectively, 25 times every 48 h. Then, seizure severity (score and latency) was calculated for the PTZ groups. A spatial working memory evaluation test (SWMET) was performed after the last injection. Hippocampus histopathology, neurogenesis, and apoptosis were demonstrated. Serum total antioxidant status (TAS) and total oxidant status (TOS) levels and the oxidative stress index (OSI) were measured. We showed that OTs and NP-OTs prevented the kindling development and had positive effects on seizure severity. SWMET-related behaviors were also recovered in the PTZ + NP-OT group. A significant increase of neurogenesis and decrease of apoptosis in the hippocampus of the PTZ + NP-OT group were observed, while OTs and NP-OTs had protective effects against PTZ-induced damage to hippocampal neurons. Our results indicate that the chronic administration of NP-OTs may have positive effects on hippocampal damage via increasing neurogenesis and decreasing apoptosis and seizure severity.
9 February 2024 in International Immunopharmacology
Background/Objectives: The key components of the blood–brain barrier (BBB) are endothelial cells, pericytes, astrocytes, and the capillary basement membrane. The BBB serves as the main barrier for drug delivery to the brain and is the most restrictive endothelial barrier in the body. Nearly all large therapeutic molecules and over 90% of small-molecule drugs cannot cross the BBB. To overcome this challenge, nanotechnology, particularly drug delivery systems such as nanoparticles (NPs), have gained significant attention. Methods: Poly(lactide-co-glycolide) (PLGA) and albumin-based NPs (bovine/human), with or without transferrin (Tf) ligands (BSA, HSA, BSA-Tf, HSA-Tf), and nanolipid carriers (NLC) were synthesized. The interactions of these NPs with human brain microvascular endothelial cells (hBMECs), human brain vascular pericytes (hBVPs), and human astrocytes (hASTROs) were analyzed. Results: At doses of 15.62 µg/mL, 31.25 µg/mL, and 62.5 µg/mL, none of the NPs caused toxic effects on hBMECs, hBVPs, or hASTROs after 3 h of incubation. All NPs were internalized by the cells, but BSA-Tf and HSA-Tf showed significantly higher uptake in hBMECs in a dose-dependent manner. Ultrastructural analysis revealed notable differences between NP formulation and cell type. Conclusions: Our findings underscore the potential of ligand-targeted NPs to selectively interact with BBB endothelial cells. Ultrastructural analysis reveals distinct cellular processing pathways for various NP formulations across BBB-associated cell types, with autophagy emerging as a crucial mechanism for NP handling in pericytes and astrocytes. Changes in NP chemical properties upon biological exposure present significant challenges for nanomedicine design, emphasizing the need for further investigation into NP interactions at the cellular and subcellular levels.
Telocytes (TCs) are characterized by a small oval-shaped cell body with long prolongations that are called telopods (Tps). PDGFR-β and c-kit markers may assist for the immunohistochemical identification of TCs; however, by these means they cannot be identified with absolute specificity. Transmission electron microscopy (TEM) is considered as a gold standard method for TCs observation. Studies on TCs in the female reproductive system are limited, and there is a lack of awareness regarding TCs in rat ovaries. We aimed to demonstrate the existence and morphology of TCs in rat ovaries, alongside previously studied TCs in rat uteri. Thus, ovaries and uteri from young adult Sprague–Dawley female rats (n = 8) with regular estrous cycles were collected. Then, left ovaries and uteri were proccessed for TEM analysis, while the right ones were used for immunohistochemistry. As a result, TCs were seen throughout the rat’s ovarian stroma with their characteristic cell bodies, Tps, podomes (Pds) and podomers (Pdms). Tps were situated within the thecal layer of the follicles, surrounding the corpus luteum and blood vessels. Ovarian TCs were recognized to have relationship with other TCs/stromal cells. Subsequently, TCs were seen in stroma of endometrium with surrounding blood vessels and uterine glands, myometrium and perimetrium in rat uteri. There was also no statistical significance between the number of c-kit+ and PDGFR-β+ telocyte-like cells in both rat ovarian (p = 0.137) and endometrial stroma (p = 0.450). Further investigation of the roles and functions of TCs in the female reproductive system is needed.
18 April 2023 in Journal of Histochemistry & Cytochemistry
Preeclampsia is a complication of pregnancy that affects 3–5% of pregnancies and is one of the major causes of maternal/neonatal mortality and morbidities worldwide. We aimed to investigate the distribution of Foxp3+ regulatory T-cells and CD68+ Hofbauer cells in the placenta of preeclamptic and healthy pregnant women with a special focus on correlating these findings with placental histology. Decidua and chorionic villi of the placenta obtained from healthy and preeclamptic pregnancies were evaluated in full-thickness sections. Sections were stained with hematoxylin and eosin and Masson’s trichrome and immunostained for Foxp3 and CD68 for histological analyses. The total histomorphological score for placentas was found to be higher in preeclamptic placentas than that in the controls. The CD68 immunoreactivity was higher in the chorionic villi of preeclamptic placentas than that in the controls. The immunoreactivity of Foxp3 was found widely distributed within the decidua in both the groups and did not differ significantly. Interestingly, Foxp3 immunoreactivity in the chorionic villi was found mainly in the villous core and, to a lesser extent, in the syncytiotrophoblasts. We found no significant relation between Foxp3 expressions and morphological changes observed in preeclamptic placentas. Although extensive research is being carried out regarding the pathophysiology of preeclampsia, the findings are still controversial.