Epidermal neural crest stem cell transplantation as a promising therapeutic strategy for ischemic stroke

Introduction: Cell-based therapy is considered as promising strategy to cure stroke. However, employing appropriate type of stem cell to fulfill many therapeutic needs of cerebral ischemia is still challenging. In this regard, the current study was designed to elucidate therapeutic potential of epidermal neural crest stem cells (EPI-NCSCs) compared to bone marrow mesenchymal stem cells (BM-MSCs) in rat model of ischemic stroke. Methods: Ischemic stroke was induced by middle cerebral artery occlusion (MCAO) for 45 minutes. Immediately after reperfusion, EPI-NCSCs or BM-MSCs were transplanted via intra-arterial or intravenous route. A test for neurological function was performed before ischemia and 1, 3, and 7 days after MCAO. Also, infarct volume ratio and relative expression of 15 selected target genes were evaluated 7 days after transplantation. Results: EPI-NCSCs transplantation (both intra-arterial and intravenous) and BM-MSCs transplantation (only intra-arterial) tended to result in a better functional outcome, compared to the MCAO group; however, this difference was not statistically significant. The infarct volume ratio significantly decreased in NCSC-intra-arterial, NCSC-intravenous and MSC-intra-arterial groups compared to the control. EPI-NCSCs interventions led to higher expression levels of Bdnf, nestin, Sox10, doublecortin, β-III tubulin, Gfap, and interleukin-6, whereas neurotrophin-3 and interleukin-10 were decreased. On the other hand, BM-MSCs therapy resulted in upregulation of Gdnf, β-III tubulin, and Gfap and down-regulation of neurotrophin-3, interleukin-1, and interleukin-10. Conclusion: These findings highlight the therapeutic effects of EPI-NCSCs transplantation, probably through simultaneous induction of neuronal and glial formation, as well as Bdnf over-expression in a rat model of ischemic strok

Effect of G-CSF on the spatial arrangement of CA1 hippocampal pyramidal neurons after brain ischemia in the male rats

Stroke is a leading cause of mortality and disability; Memory impairment occurs frequently after stroke and the pattern of hippocampal CA1 pyramidal neurons has important role in the signal transmission and memory forming. G-CSF (granulocyte-colony stimulating factor) is a novel treatment that exhibits neuroprotective and anti-apoptotic in the central nervous system. The aim of the present study was to determine the effects of G-CSF on the neurobehavioral outcome and spatial pattern of CA1 pyramidal neurons after focal cerebral ischemia in animals. Twenty one Sprague-Dawley adult male rats were randomly divided into three groups: The Sham group underwent surgery without middle cerebral artery occlusion (MCAO) and drug. The control and treatment groups after MCAO received vehicle or G-CSF (G-CSF 50 μg/kg) 6, 24, and 48 h after brain ischemia. Neurological deficit score and pole tests were performed, and 7 days after MCAO, the brain was removed and serially and coronally cut and finally stained by Nissl method. The infarct volume was evaluated and CA1 pyramidal neurons pattern was studied using Voronoi spatial tessellation in histological sections of the rat brain. The spatial pattern has been classified into regular, random, or clustered. G-CSF showed a significant effect on the weight, neurological deficit score, and Pole test and reduced infarct volume after stroke. Stroke also changed the spatial arrangement of CA1 hippocampal neurons into a random pattern, whereas treatment with G-CSF remained its regular spatial pattern. In conclusion, G-CSF had beneficial effects after cerebral ischemia on the neurological behavioral outcome, infarct volume and preserved the regular spatial distribution of CA1 hippocampal neurons. © 2019 Elsevier B.V

Expression of kisspeptin neurons in the arcuate nucleus of the goat during the follicular and luteal phases - A preliminary study

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Differential expression of RFamide-related peptide, a mammalian gonadotrophin-inhibitory hormone orthologue, and kisspeptin in the hypothalamus of Abadeh ecotype does during breeding and anoestrous seasons

Gonadotrophin-inhibitory hormone (GnIH) is a novel hypothalamic neuropeptide that was discovered in birds as an inhibitory factor for gonadotrophin release. RFamide-related peptide (RFRP) is a mammalian GnIH orthologue that inhibits gonadotrophin synthesis and release in mammals through actions on gonadotrophin-releasing hormone (GnRH) neurones and gonadotrophs, mediated via the GnIH receptor (GnIH-R), GPR147. On the other hand, hypothalamic kisspeptin provokes the release of GnRH from the hypothalamus. The present study aimed to compare the expression of RFRP in the dorsomedial hypothalamus and paraventricular nucleus (DMH/PVN) and that of kisspeptin in the arcuate nucleus (ARC) of the female goat hypothalamus during anoestrous and breeding seasons. Mature female Abadeh does were used during anoestrus, as well as the follicular and luteal phases of the cycle. The number of RFRP-immunoreactive (-IR) neurones in the follicular phase was lower than in the luteal and anoestrous stages. Irrespective of the ovarian stage, the number of RFRP-IR neurones in the rostral and middle regions of the DMH/PVN was higher than in the caudal region. By contrast, the number of kisspeptin-IR neurones in the follicular stage was greater than in the luteal stage and during the anoestrous stage. Irrespective of the stage of the ovarian cycle, the number of kisspeptin-IR neurones in the caudal region of the ARC was greater than in the middle and rostral regions. In conclusion, RFRP-IR cells were more abundant in the rostral region of the DMH/PVN nuclei of the hypothalamus, with a greater number being found during the luteal and anoestrous stages compared to the follicular stage. On the other hand, kisspeptin-IR neurones were more abundant in the caudal part of the ARC, with a greater number recorded in the follicular stage compared to the luteal and anoestrous stages

Male subfertility effects of sub-chronic ethanol exposure during stress in a rat model

Background: Stressful conditions increase alcohol consumption in men. Clinical studies link disruption of the neuroendocrine stress system with alcoholism, but the effect of alcohol in a stress condition on male fertility is still relatively poorly understood. This project was undertaken to evaluate the effect of sub-chronic alcohol in a stress condition on male fertility in a rat model. Methods: Male Sprague–Dawley rats were randomly divided into a control group, a stress group that was exposed to restraint stress, an ethanol group that was injected with ethanol daily, and a stress + ethanol group that was injected with ethanol daily and was exposed to restraint stress, simultaneously. Furthermore, testis tissue was evaluated histomorphometrically and immunohistochemically for apoptosis using a TUNEL assay after 12 days. Epididymis sperm analysis was done. Blood cortisol and testosterone were measured and expression of hypothalamic kisspeptin (Kiss1), RFRP-3, and MC4R mRNA were evaluated. Results: Ethanol exposure during restraint stress did not alter body weight. Ethanol exposure decreased the cellular diameter and area, and stress increased the cellular diameter and area, in comparison with the control group. In the stress group, in comparison with the other groups, the number of seminiferous tubules decreased and the numerical density of seminiferous tubules increased. In addition, ethanol exposure and/or stress reduced semen analysis parameters (sperm viability and motility), but did not change serum testosterone concentrations. Apoptosis increased in spermatogonia with ethanol exposure, but spermatocytes were not affected. Our data present the novel finding that ethanol and stress reduced hypothalamic Kiss1 mRNA expression, while ethanol exposure decreased hypothalamic RFRP-3 and MC4R mRNA expression. Conclusions: Ethanol decreased cortisol hormone level during the restraint stress condition and attenuated hypothalamic reproductive-related gene expressions. Therefore, ethanol exposure may induce reduction of sperm viability, increased sperm mortality, and increased apoptosis, with long-term effects, and may induce permanent male subfertility