Importance of Schedule of Administration in the Therapeutic Efficacy of Guanosine: Early Intervention After Injury Enhances Glutamate Uptake in Model of Hypoxia-ischemia |
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Authors: | M B Moretto B Boff D Lavinsky C A Netto J B T Rocha D O Souza S T Wofchuk |
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Institution: | (1) Departamento de Análises Clínicas e Toxicológicas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil;(2) Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil;(3) Departamento de Química, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil |
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Abstract: | Perinatal cerebral hypoxia–ischemia (HI) is an important cause of mortality and neurological disabilities such as cerebral
palsy, epilepsy, and mental retardation. The potential for neuroprotection in HI can be achieved mainly during the recovery
period. In previous work, we demonstrated that guanosine (Guo) prevented the decrease of glutamate uptake by hippocampal slices
of neonatal rats exposed to a hypoxic-ischemic (HI) insult in vivo when administrated before and after insult. In the present
study, we compared the effect of Guo administration only after HI using various protocols. When compared with the control,
a decrease of 3H] glutamate uptake was avoided only when three doses of Guo were administered immediately, 24 h and 48 h after insult, or
at 3 h, 24 h, and 48 h after injury or at 6 h, 24 h, and 48 h after HI. These findings indicate that early Guo administration
(until 6 h) after HI, in three doses may enhance glutamate uptake into brain slices after hypoxia/ischemia, probably resulting
in decreased excitotoxicity. |
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Keywords: | Glutamate uptake Hypoxic ischemic neonatal Brain Guanosine |
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