Browsing by Subject "Central nervous system"
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- PublicationOpen Access5-Fluorouracil-induced histopathological changes in the central nervous system of rat fetuses(Murcia : F. Hernández, 2009) Yamaguchi, Y.; Aoki, A.; Fukunaga, Y.; Matsushima, K.; Ebata, T.; Ikeya, M.; Tamura, K.5-Fluorouracil (5-FU), a thymidylate synthesis inhibitor, has been well known to induce developmental anomalies in the craniofacial tissues and limb buds. Recently it was reported that microencephaly was also induced in rat neonates after 5-Fu-treatement in late phase of pregnancy (Kumar et al., 2006). In this study, pregnant rats were treated with 5-Fu (15, 30 or 50 mg/kg) on day 13 of gestation, and their fetuses were examined for histopathological changes, especially in the fetal central nervous system (CNS) at 12, 24 and 48 hours after treatment (HAT). At 12 HAT, an enhancement of pyknosis of neuronal progenitor cells and subsequent loss of dead cells were detected in the CNS in a dose-dependent manner. The severity of such histopathological changes in the CNS was most prominent in the telencephalon (middle and dorsal layers of the ventricular zone) and spinal cord (dorsal area). Pyknotic cells decreased towards 48 HAT in the brain while they increased towards 48 HAT in the spinal cord. Almost all of the nuclei of pyknotic cells were positively stained by TUNEL method and showed characteristics of apoptotic cells under electron microscopy. Therefore, these pyknotic cells were considered to be apoptotic ones. Enhanced apoptosis and reduced mitosis in neuronal progenitor cells in the telencephalon seem to be responsible for the later induction of microencephaly reported by Kumar et al. (2006).
- PublicationOpen AccessAdenosine deaminase, not immune to a mechanistic rethink in central nervous system disorders?(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Hall, Benjamin; George, Jonathan G.; Allen, Scott P.Adenosine deaminase (ADA) is a purine metabolism enzyme that catalyses the breakdown of adenosine and deoxyadenosine. The enzyme is important in several cellular processes, including the innate immune response and cellular differentiation, and it is also an important enzyme for the maintenance of brain homeostasis, in part due to its regulation of adenosine. Aberrant regulation of ADA enzyme activity has been linked to several neurodegenerative diseases and diseases that can result in neurological impairment. However, the mechanisms behind altered ADA regulation and how this leads to the development of neurological dysfunction are poorly characterised. This review summarises the current research on ADA and its role and regulation in disease pathology, with a focus on the central nervous system (CNS) and the neurodegenerative disease, amyotrophic lateral sclerosis (ALS)
- PublicationOpen AccessAngiogenesis in the central nervous system: a role for vascular endothelial growth factor/vascular permeability factor and tenascin-C. Common molecular effectors in cerebral neoplastic and non-neoplastic “angiogenic diseases”(Murcia : F. Hernández, 2002) Zagzag, D.; Capo, V.Human pathological conditions of the central nervous system (CNS) associated with angiogenesis (i.e. neovascularization) include neoplastic, as well as infectious, ischemic, and traumatic processes. Upregulation of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) and tenascin-C (TN-C) is spatially and temporally related to neovascularization. Spatially, VEGF/VPF and TN-C are both found at the site of neovascularization, but they are not detected in areas of normal brain or in areas without neovascularization. Te m p o r a l l y, VEGF/VPF and TN-C are found at the peak of angiogenesis and are not detected when angiogenesis had ceased.
- PublicationOpen AccessCD1 S-containing glycoconjugates in the central nervous system(Murcia : F. Hernández, 1996) Gocht, A.; Struckhoff, G.; Lohler, J.CD15-containing glycoconjugates have a common trisaccharide residue, 3-fucosyl-N-acetyllactosamine, which can be recognized by a panel of monoclonal antibodies. Immunohistochemical studies revealed a widespread distribution of CD15 in several epithelial non-neural tissues as well as in the CNS. In the mature mammalian brain CD15-containing glycolipids and glycoproteins are constantly present in astrocytes, whereas oligodendrocytes and particular subpopulations of neurons are variably immunostained. CD15 immunoreactive astrocytes are spatially distributed in some brain regions, which points to specialized functions of astroglial subpopulations. The expression of CD15 follows a timely ordered pattern during the development of glial cells and neurons of certain brain areas, such as the human and rat cerebellum and the mouse visual system. During morphogenesis, CD15 may exert either growth-promoting or growthrepulsive activities to guide cell migration. In CNS lesions altered expression patterns of CD15 may occur. For example, in human gliomas the staining intensity for CD15 inversely correlates with the grade of malignancy. In degenerative brain diseases reactive astrocytes may reveal an increased labelling intensity on their cell surface as well as an abnormal cytosolic accumulation of the epitope. The functional significance of CD15 in the CNS is not exactly known yet. The carbohydrate could be involved in cellular adhesion andtor as receptor molecule in signal transduction pathways, as has recently been demonstrated for leukocyte-platelet or leukocyte-endothelial cell interactions.
- PublicationOpen AccessHuman Wharton’s jelly mesenchymal stem cells protect axotomized rat retinal ganglion cells via secretion of antiinflammatory and neurotrophic factors(Springer Nature, 2018-11-02) Millán-Rivero, J.E; Sobrado-Calvo, P.; Blanquer, M.; Moraleda, J.M.; Vidal-Sanz, M.A.; Agudo-Barriuso, M.; Nadal-Nicolás, Francisco Manuel; García Bernal, David; Oftalmología, Optometría, Otorrinolaringología y Anatomía PatológicaEl artículo muestra los resultados del estudio de la capacidad neuroprotectora de las células mesenquimales derivadas de cordón umbilical (CMCU) sobre las células ganglionares de la retina (CGR) tras axotomía por aplastamiento del nervio óptico. Se quería saber, no solo si existía efecto neuroprotector, si no también si el trasplante de estas células tenía algún efecto tóxico en retina, y dilucidar los posibles mecanismos a través de los cuales se produjeran estos efectos. En una primera parte del estudio, demostramos que las CMCU suprimen la proliferación de células T e inhiben la producción de citocinas proinflamatorias, confirmando que su efecto inmunomodulador es mayor que el de las células mesequimales derivadas de médula ósea. También observamos que tras la inyección intravítrea de CMCU, estas se integran en la capa de CGR, extendiéndose por toda la retina, observándose una reducción importante a los 30 días, y no observando la formación de tumoración. En retinas intactas no se observó efecto tóxico sobre las CGR, si bien sí hubo alteración de la arquitectura de la retina por la infiltración masiva de células Iba1+ (microglía o macrófagos), que se reduce mucho a los 30 días y da señales de restauración de dicha arquitectura. Por otra parte, en retinas axotomizadas se encontró un aumento muy importante de la supervivencia de las CGR de los animales tratados.
- PublicationOpen AccessId genes in nervous system development(Murcia : F. Hernández, 2000) Andres-Barquin, P.J.; Hernandez, M.C.; Israel, M.A.Id genes encode helix-loop-helix proteins that function to mediate processes important for normal development including cellular differentiation. proliferation and apoptosis. Id proteins act as negative regulators of other transcription factors, which are essential for cell determination and differentiation in diverse cell types, and interact with proteins important for cell cycle regulation. Studies of Id gene expression in the nervous system and in neural cells in culture indicate that Id proteins contribute to the regulation of mammalian nervous system development. Also, recognition of a wide variety of proteins with which Id transcription factors are capable of interacting suggests that it will be possible to understand more precisely their specific functions and importantly how these are integrated.
- PublicationOpen AccessMetabolomic changes in the rat retina after optic nerve crush(Association for Research in Vision and Ophthalmology, 2013-06-21) Agudo Barriuso, Marta; Lahoz, Agustín; Nadal-Nicolás, Francisco Manuel; Sobrado Calvo, Paloma; Piquer Gil, Marina; Díaz Llopis, Manuel; Vidal Sanz, Manuel; Mullor, José L.; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultades de la UMU::Facultad de MedicinaPurpose: To identify metabolic pathways and metabolites affected by optic nerve crush that can act as predictors of the disease or therapeutic targets. Methods: The left optic nerve of adult rats was intraorbitally crushed and retinas were dissected 24 hours or 14 days after the lesion (n = 10 per group). Metabolic profiling analysis was carried out by Metabolon, Inc. A total of 195 metabolites were unambiguously detected. Data were normalized and the regulated metabolites were identified after comparing the different conditions. Metabolite concentration changes were analyzed using single and multivariate statistical analysis to detect discriminatory metabolites. Functional clustering and meta-analysis of the regulated metabolites was run through the Metacore platform. Results: Comparison of 24 hours versus control, 14 days versus control samples, and 24 hours versus 14 days identified 9, 19, and 32 regulated metabolites, respectively. Single and multivariate analysis identified a total of 27 and 36 metabolites to discriminate between control and 14 days and between 24 hours and 14 days, respectively. Enrichment analysis showed alterations in the amino acid, carbohydrate, and lipid metabolism, which were further linked to translation, oxidative stress, energy (glucose and tricarboxylic acid cycle), and apoptosis through ceramide pathways. Conclusions: Our analysis differentiates a set of metabolites that clearly discriminate control and early-injury samples from late-injury samples. These metabolites could have potential use as diagnostic molecules.
- PublicationOpen AccessNutrition and hypothalamic neuropeptides in sheep: Histochemical studies(Murcia : F. Hernández, 2005) Chaillou, E.; Tillet, Y.The identification and role of neuropeptides in the control of food intake and energy balance have been extensively studied in rodents, and for more than ten years, similar studies have been performed in sheep. As a photoperiodic ruminant, sheep are an interesting alternative animal model to rodents. In this review, we summarize the results obtained in sheep concerning the distribution of peptide-containing neurones in the hypothalamus and their central role in the control of food intake and energy balance, and compared them with relevant data from rodents. Even if the general organization and the role of hypothalamic neuropeptides are similar in sheep and rodents, numerous differences have been observed between these two species. In sheep, the magnocellular neurones of the paraventricular and supraoptic nuclei are characterized by the low density and the lack of galanin- and neuropeptide-Y-containing neurones, respectively. The sheep pituitary stalk presents neurones containing neuropeptides such as neuropeptide-Y or beta-endorphin, which are also found in the deep part of the infundibular nucleus. In this structure, several neuronal populations, including galanin, agouti-gene related peptide, somatostatin, are sensitive to energy balance variations, undernutrition or overfeeding, which may specifically modify neuropeptide levels in discrete neuronal subgroups. This feature is well illustrated by the number of neuropeptide- Y labelled neurones, that increases in the lateral part of the infundibular nucleus of undernourished ewes and decreases in the ventral part of overfed ewes. Conversely, after 24 hours of food deprivation, the number of neuropeptide-Y-immunolabelled neurones is unchanged in the sheep infundibular nucleus, whereas increased levels of this neuropeptide are described, in rats, by radioimmuno-assay. In conclusion, our review shows that peptide-containing neurone systems, involved in the regulation of food intake and energy balance in sheep, are generally similar to those observed in other species, but they present specific differences according to the physiological characteristics of the animal model.
- PublicationOpen AccessPrimary central nervous system lymphomas in immunocompetent patients(Murcia : F. Hernández, 2004) Guinto, G.; Félix, I.; Aréchiga, N.; Arteaga, V.; Kovacs, K.Primary Central nervous system lymphoma is a rare non-Hodgkin’s tumor of the brain that has been traditionally found in patients with immunodeficiency syndromes. However, there are several immunocompetent patients that have also been reported with this neoplasm. In this group of patients, the mean age of diagnosis is around 60-year old, with a very slight predominance in women. Macroscopically, most of the tumors are unique and mainly located in the supratentorial region in the proximity of the cerebrospinal fluid circulation. The typical histological pattern is a perivascular distribution of tumor cells, within a network of reticulin fibers. Even though they are usually well defined masses, it is not rare to find tumor invasion beyond the macroscopic margin. Coagulative necrosis is not as common as in immunodeficiency-related cases. Immunohistochemistry has demonstrated that most of the tumor cells are Blymphocytes and the electron microscopic findings do not differ from those reported in systemic non-Hodgkin’s lymphomas. There are several histological classifications of these tumors, some of them with recent modifications to facilitate the analysis, but unfortunately, up now with a little or no clinical significance. The diagnosis is based on the histological study of the specimen obtained mainly through a Stereotactic biopsy. The treatment is based on a combination of chemotherapy followed by radiotherapy, but the mortality rate is still high.
- PublicationOpen AccessThe distribution of cholinergic neurons in the human central nervous system(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2000) Oda, Y.; Nakanishi, I.Choline acetyltransferase (ChAT), the enzyme responsible for the biosynthesis of acetylcholine, is presently the most specific marker for identifying cholinergic neurons in the central and peripheral nervous systems. The present article reviews immunohistochemical and in situ hybridization studies on the distribution of neurons ex pressing ChAT in the human central nervous system. Neurons with both immunoreactivity and in situ hybridization signals of ChAT are observed in the basal forebrain (diagonal band of Broca and nucleus basalis of Meynert), striatum (caudate nucleus, putamen and nucleus accumbens), cerebral cortex, mesopontine tegmental nuclei (pedunculopontine tegmental nucleus, laterodorsal tegmental nucleus and parabigeminal nucleus), cranial motor nuclei and spinal motor neurons. The cerebral cortex displays regional and laminal differences in the distribution of neurons with ChAT. The medial seotal nucleus and medial habenular nucleus contain immunoreactive neurons for ChAT, which are devoid of ChAT mRNA signals. This is probably because there is a small number of cholinergic neurons with a low level of ChAT gene expression in these nuclei of human. Possible connections and speculated functions of these neurons are briefly summarized.