RESUMO
Severe hypoxic-ischemic encephalopathy (HIE) is a devastating condition that can lead to mortality and long-term disabilities in term newborns. No rapid and reliable laboratory test exists to assess the degree of neuronal injury in these patients. We propose two possible biomarkers: 1) phosphorylated axonal neurofilament heavy chain (pNF-H) protein, one of the major subunits of neurofilaments, found only in axonal cytoskeleton of neurons and 2) Ubiquitin C-terminal hydrolase 1 (UCHL1 protein) that is heavily and specifically concentrated in neuronal perikarya and dendrites. High-serum pNF-H and UCHL1 levels are reported in subarachnoid hemorrhage and traumatic brain injury, suggesting that they are released into blood following neuronal injury. We hypothesized that serum pNF-H and UCHL1 were higher in neonates with moderate-to-severe HIE than in healthy neonates. A time-limited enrollment of 14 consecutive patients with HIE and 14 healthy controls was performed. UCHL1 and pNF-H were correlated with clinical data and brain MRI. UCHL1 and pNF-H serum levels were higher in HIE versus controls. UCHL1 showed correlation with the 10-min Apgar score, and pNF-H showed correlation with abnormal brain MRI. Our findings suggest that serum UCHL1 and pNF-H could be explored as diagnostic and prognostic tools in neonatal HIE.
Assuntos
Biomarcadores/sangue , Hipóxia-Isquemia Encefálica/sangue , Recém-Nascido/sangue , Animais , Feminino , Humanos , Masculino , Proteínas de Neurofilamentos/metabolismo , Projetos Piloto , Ubiquitina Tiolesterase/metabolismoRESUMO
The neutral amino acid transporters SNAT1-3 and ASCT1 play critical roles in the recycling of glutamine, and subsequently glutamate, via the glutamine-glutamate cycle. Hypoxia-ischemia was induced in rat pups using the Rice-Vannucci model. Brains were harvested at 1 h, 24 h and 7 days after ischemia. The expression of NAATs was evaluated using immunoblotting, real-time PCR, and immunohistochemistry. Results were compared with age-matched controls and shams. SNAT1 mRNA decreased at 1 h after injury in both hemispheres when compared with the control animals and correlated with a decrease in protein expression at 24 h in the hippocampus and cortex. SNAT1 protein expression increased globally at 7 days after injury and specifically in the hippocampus. Finally, SNAT2 and 3 demonstrated subtle changes in various brain regions after injury. These data suggest that neutral amino acid transporters remain largely intact after hypoxia-ischemia.
Assuntos
Sistema A de Transporte de Aminoácidos/metabolismo , Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiologia , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/fisiopatologia , Sistema A de Transporte de Aminoácidos/genética , Sistema ASC de Transporte de Aminoácidos/genética , Sistema ASC de Transporte de Aminoácidos/metabolismo , Sistemas de Transporte de Aminoácidos/genética , Sistemas de Transporte de Aminoácidos/metabolismo , Sistemas de Transporte de Aminoácidos Neutros/genética , Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Aminoácidos Neutros/metabolismo , Animais , Regulação da Expressão Gênica no Desenvolvimento , Immunoblotting , Imuno-Histoquímica , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Hypoxic-ischemic encephalopathy (HIE) in neonates results in long-term disabilities. Stem cell therapy may offer an attractive treatment for HIE. Multipotent astrocytic stem cells (MASCs) from mice transplanted into a rat model of hypoxia-ischemia (HI) survived the transplantation and showed signs of migration towards the injured cortex. Some MASCs around the injured cortex differentiated into neuronal and astrocytic phenotypes. MASCs transplanted into non-ischemic pups survived but retained their astrocytic phenotype. These data suggest that transplanted MASCs can survive and differentiate into neurons and astrocytes in the post-injury milieu of the neonatal brain injured by HI.
