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01.06.2007 | Research Article

Plasticity of basal ganglia neurocircuitries following perinatal asphyxia: effect of nicotinamide

verfasst von: Verena Klawitter, Paola Morales, Diego Bustamante, Sonia Gomez-Urquijo, Tomas Hökfelt, Mario Herrera-Marschitz

Erschienen in: Experimental Brain Research | Ausgabe 1/2007

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Abstract

The potential neuroprotection of nicotinamide on the consequences of perinatal asphyxia was investigated with triple organotypic cultures. Perinatal asphyxia was induced in vivo by immersing foetuses-containing uterine horns removed from ready-to-deliver rats into a water bath for 20 min. Sibling caesarean-delivered pups were used as controls. Three days later tissue from substantia nigra, neostriatum and neocortex was dissected and placed on a coverslip. After a month, the cultures were processed for immunocytochemistry and phenotyped with markers against the NMDA receptor subunit NR1, tyrosine hydroxylase (TH), or neuronal nitric oxide synthase (nNOS). Some cultures were analysed for cell viability. Nicotinamide (0.8 mmol/kg, i.p.) or saline was administered to asphyxia-exposed and caesarean-delivered control pups 24, 48 and 72 h after birth. Perinatal asphyxia produced a decrease of cell viability in substantia nigra, but not in neostriatum or neocortex. Immunocytochemistry confirmed the vulnerability of the substantia nigra, demonstrating that there was a significant decrease in the number of NR1 and TH-positive (+) cells/mm², as well as a decrease in the length of TH⁺ processes, suggesting neurite atrophy. In control cultures, many nNOS⁺ cells were seen, with different features, regional distribution and cell body sizes. Following perinatal asphyxia, there was an increase in the number of nNOS⁺ cells/mm² in substantia nigra, versus a decrease in neostriatum including reduced neurite length, and no apparent changes in neocortex. The main effect of nicotinamide was seen in the neostriatum, preventing the asphyxia-induced decrease in the number of nNOS⁺ cells and neurite length. Nicotinamide also prevented the effect of perinatal asphyxia on TH-positive neurite length. The present results support the idea that nicotinamide can prevent the effects produced by a sustained energy-failure condition, as occurring during perinatal asphyxia.

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Titel: Plasticity of basal ganglia neurocircuitries following perinatal asphyxia: effect of nicotinamide
verfasst von: Verena Klawitter
Paola Morales
Diego Bustamante
Sonia Gomez-Urquijo
Tomas Hökfelt
Mario Herrera-Marschitz
Publikationsdatum: 01.06.2007
Verlag: Springer-Verlag
Erschienen in: Experimental Brain Research / Ausgabe 1/2007
Print ISSN: 0014-4819
Elektronische ISSN: 1432-1106
DOI: https://doi.org/10.1007/s00221-006-0842-7

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