Genetic Aspects of Glial Cells Regarding Neurodegenerative Diseases.

Glial cells (also known as glia or neuroglia) are structures which are found in large numbers throughout the nervous system, fulfilling multiple functions, such as regulating the synapses, providing structure, support and nutrition, contributing towards the immune response and tissue oxygenation. Knowledge regarding glial cells has increased during the last few years, since Virchow defined them as supporting connective tissue, followed by Ramón y Cajal who described them as tissue in themselves, until today when a first order physiological role has been recognised for them and a leading role in the appearance and progression of various pathological processes, primarily in the group of Neurodegenerative Diseases (ND). The ND represents a group of pathologies which gradually cause the degeneration of nervous tissue, have a broad spectrum regarding their appearance and, in some cases, are the direct consequence of genetic alterations leading to physiological changes in the nervous system. The present article has thus been aimed at describing glial cells' genetic interaction with ND through a systemic review of the pertinent literature. The mechanisms through which the different classes of glial cells become involved in the appearance of ND are poorly understood; however, evidence indicates that their role could be a critical factor in these pathologies' appearance, regulation and chronicity, these being largely determined by different types of cellular interactions and interaction with the microenvironment. This review shows that ND genetics regarding glial cells' cellular, molecular and genetic functioning represents a complex and understudied process; studying these factors could be a key step for ascertaining the origin of these pathologies, thereby leading to more effective therapies being developed.

Effects of Excitotoxic Lesion with Inhaled Anesthetics on Nervous System Cells of Rodents.

Different anesthesia methods can variably influence excitotoxic lesion effects on the brain. The main purpose of this review is to identify potential differences in the toxicity to nervous system cells of two common inhalation anesthesia methods, isoflurane and sevoflurane, used in combination with an excitotoxic lesion procedure in rodents. The use of bioassays in animal models has provided the opportunity to examine the role of specific molecules and cellular interactions that underlie important aspects of neurotoxic effects relating to calcium homeostasis and apoptosis activation. Processes induced by NMDA antagonist drugs involve translocation of Bax protein to mitochondrial membranes, allowing extra-mitochondrial leakage of cytochrome C, followed by sequence of changes that ending in activation of CASP-3. The literature demonstrates that the use of these anesthetics in excitotoxic surgery increases neuroinflammation activity facilitating the effects of apoptosis and necrosis on nervous system cells, depending on the concentration and exposure duration of the anesthetic. High numbers of microglia and astrocytes and high levels of proinflammatory cytokines and caspase activation possibly mediate these inflammatory responses. However, it is necessary to continue studies in rodents to understand the effect of the use of inhaled anesthetics with excitotoxic lesions in different developmental stages, including newborns, juveniles and adults. Understanding the mechanisms of regulation of cell death during development can potentially provide tools to promote neuroprotection and eventually achieve the repair of the nervous system in pathological conditions.

Gliomas: New Perspectives in Diagnosis, Treatment and Prognosis.

Gliomas are central nervous system tumors originated from glial cells, whose incidence and mortality is expected to rise in coming years, especially in developing countries. Diagnosis and classification of gliomas have largely relied on tumor histopathologic features that provide limited information regarding response to therapy or prognosis. Current treatment of gliomas is surgery combined with chemotherapy and/or radiotherapy. However, many tumors show a high resistance to these interventions, and recurrences are frequent since conventional therapies do not take into account the unique molecular features of different subtypes of glioma. Molecular genetics provide new insights in classifying gliomas and predicting response to therapy that can range from conventional treatments to new revolutionary therapeutic approaches. This article offers a review of the intracellular signaling pathways involved in carcinogenesis of gliomas, as well as a description of new tools for their diagnosis, prognosis, and treatment with a target-oriented approach.

Novel Approaches in Astrocyte Protection: from Experimental Methods to Computational Approaches.

Astrocytes are important for normal brain functioning. Astrocytes are metabolic regulators of the brain that exert many functions such as the preservation of blood-brain barrier (BBB) function, clearance of toxic substances, and generation of antioxidant molecules and growth factors. These functions are fundamental to sustain the function and survival of neurons and other brain cells. For these reasons, the protection of astrocytes has become relevant for the prevention of neuronal death during brain pathologies such as Parkinson's disease, Alzheimer's disease, stroke, and other neurodegenerative conditions. Currently, different strategies are being used to protect the main astrocytic functions during neurological diseases, including the use of growth factors, steroid derivatives, mesenchymal stem cell paracrine factors, nicotine derivatives, and computational biology tools. Moreover, the combined use of experimental approaches with bioinformatics tools such as the ones obtained through system biology has allowed a broader knowledge in astrocytic protection both in normal and pathological conditions. In the present review, we highlight some of these recent paradigms in assessing astrocyte protection using experimental and computational approaches and discuss how they could be used for the study of restorative therapies for the brain in pathological conditions.

[Pathogenesis of spinal cord injuries and mechanisms of repair induced by olfactory ensheathing cells]. / Patogenia de la lesion medular y mecanismos de reparacion inducidos por las celulas de la glia envolvente olfatoria.

INTRODUCTION: Spinal cord injury is a catastrophic event with permanent consequences during the all life. Treatment research has been based in the development of therapies that reduce the discapacity, but since the nineties there has been an important advance and several cellular transplants have been tested in spinal cord animal models, like Schwann cells, astrocytes and olfactory and olfactory ensheathing cells (OEC). AIM: Detailed account of spinal cord injury pathogeny, primary and secondary, and the OEC mechanisms for the regeneration effects that have been described in the literature. DEVELOPMENT: After the trauma, spinal cord injury develops in two phases, the primary injury with characteristics compression lesions, and the secondary produce for several factors that occur in parallel and include: vascular, cellular and molecular factors, and glial scar formation. The most of spinal cord models and OEC transplants have been reported functional recovery, remielinization and axonal regeneration. These cells exert their action in a direct way by producing grow factors and in an indirect way inducing directly neuronal an axonal regeneration and remielinization. CONCLUSIONS: OEC are a therapeutic option in patients with spinal cord injury, because they induce in a direct or indirect way, neuronal and axonal regeneration, remielinization, decrease the glial scar and produce other effects that conduce a functional recovery.

TITLE: Patogenia de la lesion medular y mecanismos de reparacion inducidos por las celulas de la glia envolvente olfatoria.Introduccion. La lesion medular es un evento catastrofico, cuyas consecuencias persisten durante toda la vida del paciente. La investigacion en tratamiento se ha basado principalmente en el desarrollo de terapias que reduzcan la discapacidad, pero desde los anos noventa hay un avance significativo y se han probado varios trasplantes celulares en modelos animales de lesion medular, celulas de Schwann, astrocitos y celulas de la glia envolvente olfatoria (CGEO). Objetivo. Hacer un recuento detallado de la patogenia de la lesion medular primaria y secundaria y de los mecanismos por los cuales las CGEO inducirian sus posibles efectos regenerativos descritos en la bibliografia. Desarrollo. Despues del traumatismo, la lesion se desarrolla en dos fases, la primaria se caracteriza por las lesiones de compresion y la secundaria se produce por una serie de factores que se dan en paralelo y que incluyen factores vasculares, celulares, moleculares y formacion de cicatriz glial. La mayoria de los modelos de lesion medular y trasplante con CGEO han comunicado recuperacion funcional, remielinizacion y regeneracion axonal. Estas celulas ejercen su accion de manera indirecta a traves de la produccion de factores de crecimiento y de manera directa induciendo regeneracion neuronal, axonal y remielinizacion. Conclusiones. Las CGEO son una opcion terapeutica en pacientes con lesion medular debido a que inducen de modo directo o indirecto regeneracion neuronal, axonal, remielinizacion de axones, disminucion de cicatriz glial y otros efectos que conducen a la recuperacion funcional.

Efectos de múltiples exposiciones a sevoflurano a dosis sub-CAM en la neuroapoptosis y la función cognitiva en el periodo neonatal / Effects of multiple exposures to sevoflurane at sub-MAC doses on neuroapoptosis and cognitive function during the neonatal period

Introducción: Recientes estudios han sugerido que los niños con múltiples exposiciones anestésicas tienen un mayor riesgo de deterioro neurocognitivo. Objetivo: Analizar los efectos neurodegenerativos a nivel histológico, cognitivo y del comportamiento posterior a exposiciones repetidas al sevoflurano a dosis inferiores a la concentración alveolar minina en ratas neonatales. Métodos: Se expusieron ratas Wistar de 5-7 días durante una hora a sevoflurano al 2,3%; una, 2 o 3 veces con intervalos de 24 h entre exposición. Posteriormente se determinó el efecto del anestésico en la neuroapoptosis mediante marcación inmunohistoquímica con caspasa-3, Fox-3 y CD95. El aprendizaje fue evaluado con el laberinto acuático de Morris, y el comportamiento relacionado a ansiedad, con laberinto elevado en cruz. Resultados: En todos los grupos experimentales se evidenció apoptosis neuronal medida por caspasa-3, siendo más marcada en el grupo de sevoflurano y en grupos de primera exposición. En laberinto elevado en cruz se encontró un tiempo total de permanencia en brazos abiertos (t test p = 0,113) estadísticamente no significativo con respecto al grupo control. En el laberinto acuático de Morris se encontró diferencia estadísticamente significativa (t test p < 0,001) cuando se compara el tiempo de realización de la prueba con respecto al grupo control. Conclusiones: La exposición a sevoflurano en ratas neonatales durante periodos cortos y repetidos induce muerte neuronal posiblemente por apoptosis a través de la activación de caspasa-3. Como consecuencia produce déficit de aprendizaje, principalmente en la adquisición de memoria espacial.

Introduction: Recent studies have suggested that children who are exposed multiple times to anesthesia have an increased risk of neurocognitive impairment. Objective: To analyze at a histological level the neurodegenerative, cognitive and behavioral effects following repeated exposures to sevoflurane at doses below the minimum alveolar concentration in neonatal rats. Methods: Wistar rats were exposed to 2.3% sevoflurane, one, two or three times for 1 h, in the course of 5-7 days, with 24-h intervals between each exposure. The neuroapoptotic effect of the anesthetic agent was subsequently determined using immunohistochemical labeling with caspase-3, Fox-3 and CD95. Learning was assessed with the Morris Water Maze, and the anxiety-related behavior was assessed with the Elevated Plus-Maze. Results: Every experimental group showed evidence of neuronal apoptosis measured withcaspase-3; however, the apoptosis was more evident in the sevoflurane group and in the first exposure groups. The total time spent in the open arms of the Elevated Plus-Maze (t test p = 0.113) was not statistically significant as compared to the control group. When comparing the test time vs. the control group, the Morris Water Maze showed a statistically significant difference (t test p < 0.001). Conclusions: Sevoflurane exposure of neonate rats for short and repeated time intervals induces neuronal death probably due to apoptosis, through caspase-3 activation. This results in learning deficit, particularly in terms of spatial memory acquisition.