Stereological Evidence of Non-Selective Hippocampal Neurodegeneration, IGF-1 Depletion, and Behavioral Deficit following Short Term Bilateral Adrenalectomy in Wistar Rats

The development of animal models to study cell death in the brain is a delicate task. One of the models, that was discovered in the late eighties, is the induction of neurodegeneration through glucocorticoid withdrawal by adrenalectomy in albino rats. Such a model is one of the few noninvasive models for studying neurodegeneration. In the present study, using stereological technique and ultrastructural examination, we aimed to investigate the impact of short-term adrenalectomy (2 weeks) on different hippocampal neuronal populations in Wistar rats. In addition, the underlying mechanism(s) of degeneration in these neurons were investigated by measuring the levels of insulin-like growth factor-1 (IGF-1) and β-nerve growth factor (β-NGF). Moreover, we examined whether the biochemical and histological changes in the hippocampus, after short-term adrenalectomy, have an impact on the cognitive behavior of Wistar rats. Stereological counting in the hippocampus revealed significant neuronal deaths in the dentate gyrus and CA4/CA3, but not in the CA2 and CA1 areas, 7 and 14 days post adrenalectomy. The ultrastructural examinations revealed degenerated and degenerating neurons in the dentate, as well as CA4, and CA3 areas, over the course of 3, 7 and 14 days. The levels of IGF-1 were significantly decreased in the hippocampus of ADX rats 24 h post adrenalectomy, and lasted over the course of two weeks. However, β-NGF was not affected in rats. Using a passive avoidance task, we found a cognitive deficit in the ADX compared to the SHAM operated rats over time (3, 7, and 14 days). In conclusion, both granule and pyramidal cells were degenerated in the hippocampus following short-term adrenalectomy. The early depletion of IGF-1 might play a role in hippocampal neuronal degeneration. Consequently, the loss of the hippocampal neurons after adrenalectomy leads to cognitive deficits

Protective effects of melatonin and omega-3 on the hippocampus and the cerebellum of adult Wistar albino rats exposed to electromagnetic fields

The purpose of the study was to investigate the effects of pulsed digital electromagnetic radiation emitted by mobile phones on the central nervous system of the adult Wistar albino rats. The study evaluated structural and functional impacts of four treatment arms: electromagnetic field (EMF) exposed; EMF exposed + melatonin treated group (EMF + Mel); EMF exposed + omega-3 (ω3) treated group (EMF + ω3); and control group (Cont). The 12-weeks-old rats were exposed to 900 MHz EMF for 60 min/day (4:00–5:00 p.m.) for 15 days. Stereological, biochemical and electrophysiological techniques were applied to evaluate protective effects of Mel and ω3. Significant cell loss in the CA1 and CA2 regions of hippocampus were observed in the EMF compared to other groups (p 0.05). The passive avoidance test showed that entrance latency into the dark compartment was significantly shorter in the EMF (p < 0.05). Additionally, EMF had a higher serum enzyme activity than the other groups (p < 0.01). In conclusion, our analyses confirm that EMF may lead to cellular damage in the hippocampus and the cerebellum, and that Mel and ω3 may have neuroprotective effects

A Study on the toxic effect of different doses of diclofenac sodium on the development of the Kidney in the Postnatal period

The toxic effects of different doses of diclofenac sodium (DS) on the kidney on the postnatal period (0-7 days) by morphometrical and immunohistochemical methods were investigated. For this purpose, 15 female adult wistar albino rats were used and divided into 5 main groups. Group Ia served as normal control, physiologic group Ib received normal saline, group II received low dose (3.9 mg/kg), group III received medium dose (9 mg/kg) and group IV received high dose (18 mg/kg). Male offspring’s from 0-7 days after birth were used in this study. On the 8th day of postnatal life, all animals were anesthetized. Then, the kidney samples were analyzed. Haematoxylin and eosin staining showed degeneration and necrosis, apparent atrophy of the glomeruli, mononuclear cell infiltration, congested vessels, increased fibrous tissue and distortion of the proximal convoluted tubules with interruption of the brush margin of the DS treated group. Increased level of Caspase-3 and upregulation of TNF-α with different doses of DS. In light of our findings, DS may lead to adverse effects that are dose-dependent in the prenatal subjected kidney to this drug

Neuroprotective effects of melatonin and omega-3 on hippocampal cells prenatally exposed to 900?MHz electromagnetic fields.

Purpose: Adverse effects on human health caused by electromagnetic fields (EMF) associated with the use of mobile phones, particularly among young people, are increasing all the time. The potential deleterious effects of EMF exposure resulting from mobile phones being used in close proximity to the brain require particular evaluation. However, only a limited number of studies have investigated the effects of prenatal exposure to EMF in the development of the pyramidal cells using melatonin (MEL) and omega-3 (ω-3). Materials and methods: We established seven groups of pregnant rats consisting of three animals each; control (CONT), SHAM, EMF, EMF + MEL, MEL, EMF + ω-3 and ω-3 alone. The rats in the EMF, EMF + MEL, EMF + ω-3 groups were exposed to 900 MHz EMF for 60 min/day in an exposure tube during the gestation period. The CONT, MEL and ω-3 group rats were not placed inside the exposure tube or exposed to EMF during the study period. After delivery, only spontaneously delivered male rat pups were selected for the establishment of further groups. Each group of offspring consisted of six animals. The optical fractionator technique was used to determine total pyramidal neuron numbers in the rat hippocampal region. Results: The total number of pyramidal cells in the cornu ammonis (CA) in the EMF group was significantly lower than in the CONT, SHAM, EMF + MEL, and EMF + ω-3 groups. No significant difference was observed between the EMF, MEL and ω-3 groups. No difference was also observed between any groups in terms of rats' body or brain weights. Conclusion: MEL and ω-3 can protect the cell against neuronal damage in the hippocampus induced by 900 MHz EMF. However, further studies are now needed to evaluate the chronic effects of 900 MHz EMF on the brain in the prenatal period

Effects of spermine and the passive avoidance learning (PAL) following cerebral ischemia in chicks: Association with neuroprotection of pyramidal cells

WOS: 000427664300005PubMed ID: 29126816The aim of this study is to investigate the effects of spermine and the passive avoidance learning on hippocampus following transient cerebral ischemia in the chicks. The study is composed of the pure control (CG), sham (SG) and experimental groups (n = 20). Experimental groups (ischemia group, IG and ischemia-spermine group, ISG) were exposed to ischemia for 20 min whereas the SG was exposed to sham operation and CG group was not exposed to any operation. Passive avoidance learning (PAL) was applied to the half number of the subjects in each group. Both before and after 7 days from the ischemia, operated animals were taken to PAL and then they were sacrificed. Total numbers of neurons in the hippocampus were stereologically estimated using Cresyl violet stained sections. We detected that number of neurons was increased following PAL and especially spermine treatment. According to our results, we suggested that spermine may reduce the deleterious effects of the ischemia by causing to increase in the neuronal number and so, it may be slightly supportive to the PAL.Ondokuz Mayis University [PYO. TIP. 1901.09.015]The Animal Ethics Committee of Yuzuncu Yil University approved the protocol and appropriate measures were taken to minimize pain or discomfort of the animals by our study group. The experimental part of this study and stereological examination was performed at Ondokuz Mayis University, Department of Histology and Embryology. This study was supported by Ondokuz Mayis University, (PYO. TIP. 1901.09.015)

Stereological Evidence of Non-Selective Hippocampal Neurodegeneration, IGF-1 Depletion, and Behavioral Deficit following Short Term Bilateral Adrenalectomy in Wistar Rats

The development of animal models to study cell death in the brain is a delicate task. One of the models, that was discovered in the late eighties, is the induction of neurodegeneration through glucocorticoid withdrawal by adrenalectomy in albino rats. Such a model is one of the few noninvasive models for studying neurodegeneration. In the present study, using stereological technique and ultrastructural examination, we aimed to investigate the impact of short-term adrenalectomy (2 weeks) on different hippocampal neuronal populations in Wistar rats. In addition, the underlying mechanism(s) of degeneration in these neurons were investigated by measuring the levels of insulin-like growth factor-1 (IGF-1) and β-nerve growth factor (β-NGF). Moreover, we examined whether the biochemical and histological changes in the hippocampus, after short-term adrenalectomy, have an impact on the cognitive behavior of Wistar rats. Stereological counting in the hippocampus revealed significant neuronal deaths in the dentate gyrus and CA4/CA3, but not in the CA2 and CA1 areas, 7 and 14 days post adrenalectomy. The ultrastructural examinations revealed degenerated and degenerating neurons in the dentate, as well as CA4, and CA3 areas, over the course of 3, 7 and 14 days. The levels of IGF-1 were significantly decreased in the hippocampus of ADX rats 24 h post adrenalectomy, and lasted over the course of two weeks. However, β-NGF was not affected in rats. Using a passive avoidance task, we found a cognitive deficit in the ADX compared to the SHAM operated rats over time (3, 7, and 14 days). In conclusion, both granule and pyramidal cells were degenerated in the hippocampus following short-term adrenalectomy. The early depletion of IGF-1 might play a role in hippocampal neuronal degeneration. Consequently, the loss of the hippocampal neurons after adrenalectomy leads to cognitive deficits

A real-life Turkish experience of venetoclax treatment in high-risk myelodysplastic syndrome and acute myeloid leukemia

Venetoclax is a selective B-cell lymphoma 2 (BCL2) inhibitor, which is approved to treat elderly patients with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). A total of 60 patients with a median age of 67 years from different centers were included in the final analysis. Our real-life data support the use of venetoclax in patients with both newly diagnosed and relapsed high-risk MDS and AML. Introduction: Venetoclax is a selective B-cell lymphoma 2 (BCL2) inhibitor, which is approved to treat elderly patients with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) in combination with either low-dose cytarabine (ARA-C) or hypomethylating agents. We aimed to collect and share data among the efficacy and safety of venetoclax both as a monotherapy or in combination with other drugs used to treat high-risk MDS or AML. Materials and Methods: A total of 60 patients with a median age of 67 (30-83) years from 14 different centers were included in the final analysis. Thirty (50%) of the patients were women; 6 (10%) of the 60 patients were diagnosed with high-risk MDS and the remaining were diagnosed with AML. Results: The best objective response rate (complete remission [CR], complete remission with incomplete hematological recovery (CRi), morphological leukemia-free state [MLFS], partial response [PR]) was 35% in the entire cohort. Best responses achieved during venetoclax per patient number were as follows: 7 CR, 1 CRi, 8 MLFS, 5 PR, and stable disease. Median overall survival achieved with venetoclax was 5 months in patients who relapsed and not achieved in patients who were initially treated with venetoclax. Nearly all patients (86.7%) had experienced a grade 2 or more hematologic toxicity. Some 36.7% of these patients had received granulocyte colony stimulating factor (GCSF) support. Infection, mainly pneumonia (26.7%), was the leading nonhematologic toxicity, and fatigue, diarrhea, and skin reactions were the others reported. Conclusion: Our real-life data support the use of venetoclax in patients with both newly diagnosed and relapsed high-risk MDS and AML