Assuntos
Homocistinúria/complicações , Hiper-Homocisteinemia/etiologia , Complicações Cardiovasculares na Gravidez/etiologia , Trombose dos Seios Intracranianos/etiologia , Adulto , Anticoagulantes/uso terapêutico , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/etiologia , Feminino , Ácido Fólico/uso terapêutico , Homocistinúria/diagnóstico , Homocistinúria/tratamento farmacológico , Homocistinúria/genética , Humanos , Hiper-Homocisteinemia/diagnóstico , Hiper-Homocisteinemia/tratamento farmacológico , Imageamento por Ressonância Magnética , Período Pós-Parto , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Piridoxina/uso terapêutico , Recidiva , Trombose dos Seios Intracranianos/diagnóstico , Trombose dos Seios Intracranianos/tratamento farmacológico , Terapia Trombolítica , Resultado do Tratamento , Complexo Vitamínico B/uso terapêutico , Vitamina K/antagonistas & inibidoresRESUMO
Hyperammonemia in neonates and infants affects brain development and causes mental retardation. We report that ammonium impaired cholinergic axonal growth and altered localization and phosphorylation of intermediate neurofilament protein in rat reaggregated brain cell primary cultures. This effect was restricted to the phase of early maturation but did not occur after synaptogenesis. Exposure to NH4Cl decreased intracellular creatine, phosphocreatine, and ADP. We demonstrate that creatine cotreatment protected axons from ammonium toxic effects, although this did not restore high-energy phosphates. The protection by creatine was glial cell-dependent. Our findings suggest that the means to efficiently sustain CNS creatine concentration in hyperammonemic neonates and infants should be assessed to prevent impairment of axonogenesis and irreversible brain damage.