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      Neuropatía óptica inducida por exposición prenatal a drogas o alcohol Translated title: Optic neuropathy induced by prenatal drug or alcohol exposure

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          Abstract

          Objetivo: Nos proponemos analizar los mecanismos celulares y moleculares implicados en el desarrollo de la retina y el nervio óptico, y las consecuencias de un consumo abusivo de metanfetamina (MA) o alcohol (EtOH) durante la gestación sobre el sistema visual en desarrollo. Material y métodos: Ratas Wistar fueron expuestas a MA o EtOH durante la gestación y lactancia para obtener su descendencia. Los globos oculares y nervios ópticos de neonatos (días 7, 14, 21 postnatales) fueron procesados para técnicas morfológicas, morfométricas y Western Blot, utilizando anticuerpos frente a la proteína fibrilar ácida de la glía (GFAP) y proteína básica de la mielina (MBP) y proteína de los neurofilamentos (NFP). Resultados: Observamos diferencias estadísticamente significativas entre el grupo expuesto a MA y expuesto a EtOH frente a los controles. El tamaño de la sección transversal del nervio óptico fue inferior en relación a la exposición a drogas o alcohol. La expresión de GFAP y MBP está alterada en los animales expuestos a drogas o alcohol, respecto a los controles. Conclusiones: La exposición prenatal a psicoestimulantes o alcohol altera el desarrollo de la retina y nervio óptico.

          Translated abstract

          Purpose: The main aim of this work was to analyse the cellular and molecular mechanisms involved in retinal and optic nerve development, and the consequences of methamphetamine «ice» (MA) or alcohol (EtOH) abuse during pregnancy on the developing visual system. Material and methods: Wistar rats were exposed to MA or EtOH during gestation and lactation and their offspring studied. Control isocaloric rats were maintained in parallel. The eyes and optic nerves from pups (at 7, 14 and 21 postnatal days) were processed using morphologic, morphometric and western blot approaches using antibodies against glial fibrillary acidic protein (GFAP), myelin basic protein (MBP) and neurofilament protein (NFP). Results: Statistically significant differences were observed between the methamphetamine-exposed and the alcohol-exposed rats, as compared to the controls. The optic nerve cross-sectional area was smaller in the drug or alcohol-exposed animals. The expression of developmental protein markers (GFAP and MBP) in the retina and optic nerve displayed striking alterations related to drug or alcohol abuse during gestation and lactation. Conclusions: Psychostimulant and alcohol exposure alters the development of the retina and optic nerve.

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          Alcohol-induced neuronal loss in developing rats: increased brain damage with binge exposure.

          A rat model of third trimester fetal alcohol exposure was used to determine whether a smaller daily dose of alcohol can induce more severe microencephaly and neuronal loss than a larger dose, if the small dose is consumed in such a way that it produces higher blood alcohol concentrations (BACs). The possibility of regional differences within the developing brain to alcohol-induced neuronal loss was also investigated. Sprague-Dawley rat pups were reared artificially over postnatal Days 4-10 (a period of rapid brain growth similar to that of the human third trimester). Two groups received a daily alcohol dose of 4.5 g/kg, administered either as a 5.1% solution in four of the 12 daily feedings or as a 10.2% solution in two of the 12 feedings. A third group received a higher daily dose (6.6 g/kg) administered as a 2.5% solution in every feeding. Gastrostomy and suckle controls were also reared. On postnatal Day 10, the animals were perfused, and brain weights were obtained. In the hippocampal formation, cell counts were made of the pyramidal cells of fields CA1 and CA2/3, the multiple cell types of CA4 and the granule cells of the dentate gyrus. In the cerebellum, Purkinje cells and granule cells were counted in each of the ten lobules of the vermis. The lower daily dose (4.5 g/kg) condensed into two or four feedings produced high maximum BACs (means of 361.6 and 190.7 mg/dl, respectively) and significant microencephaly and cell loss, relative to controls. The higher daily dose (6.6 g/kg), administered continuously, resulted in low BACs (mean of 39.2 mg/dl) and induced no microencephaly or cell loss. Regional differences in neuronal vulnerability to alcohol were evident. In the hippocampus, CA1 neuronal number was significantly reduced only by the most condensed alcohol treatment, while CA3, CA4, and the dentate gyrus populations were not reduced with any alcohol treatment. In the cerebellum, some lobules suffered significantly greater Purkinje cell loss and granule cell loss than did others. The regions in which Purkinje cells were most mature at the time of the alcohol exposure were the most vulnerable to Purkinje cell loss.
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            OPHTHALMIC INVOLVEMENT IN THE FETAL ALCOHOL SYNDROME: CLINICAL AND ANIMAL MODEL STUDIES

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              Expression of MBP, PLP, MAG, CNP, and GFAP in the Human Alcoholic Brain.

              Chronic and excessive alcohol misuse results in neuropathological damage in the cerebral cortex. The damage includes white matter loss, brain atrophy, and selective loss of neurons in the superior frontal gyrus. Chronic alcohol misuse also results in alterations in the expression of a number of genes, including a selective reprogramming of myelin gene expression in the frontal cortex. The expression of cyclic nucleotide phosphodiesterase, glial fibrillary acidic protein, myelin-associated glycoprotein, myelin basic protein, and myelin proteolipid protein were assessed in the superior frontal gyrus and the primary motor cortex of control, uncomplicated alcoholic, and cirrhotic alcoholic cases. Overall, the expression of cyclic nucleotide phosphodiesterase, glial fibrillary acidic protein, myelin-associated glycoprotein, and myelin basic protein were significantly lower in the cirrhotic alcoholic cases compared with controls, with a similar tendency for myelin proteolipid protein. There was a strong correlation between the expression of the proteins studied and the brain weight of the individual case, but this interaction did not confound the overall analysis. There was no significant difference between controls and uncomplicated alcoholics. The loss of myelin proteins occurred without gross changes in brain pathology or brain weight and was not restricted to pathologically susceptible brain regions. It is not possible to determine whether the loss of myelin proteins in cirrhotic alcoholics is the result of cirrhosis per se or the combination of alcohol misuse and liver cirrhosis. Future studies comparing cases with alcoholic and nonalcoholic cirrhosis of the liver disease are required to elucidate this further.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                aseo
                Archivos de la Sociedad Española de Oftalmología
                Arch Soc Esp Oftalmol
                Sociedad Española de Oftalmología (, , Spain )
                0365-6691
                January 2007
                : 82
                : 1
                : 21-26
                Affiliations
                [02] Algeciras orgnameHospital Universitario Punta de Europa orgdiv1Departamento de Oftalmología España
                [01] Valencia orgnameUnidad de Investigación Oftalmológica Santiago Grisolía España
                Article
                S0365-66912007000100005
                10.4321/s0365-66912007000100005
                fe38507f-2d56-4121-ad08-d58f4475918e

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 International License.

                History
                : 17 January 2007
                : 05 April 2006
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 16, Pages: 6
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                SciELO Spain


                Neuropatía óptica,metanfetamina,psicoestimulantes,alcohol,síndrome tóxico gestacional,Optic neuropathy,methamphetamine,psychostimulants,gestational toxic syndrome

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