Oxidative stress in the human fetal brain: an immunohistochemical study

Yamamoto, Tomoko; Shibata, Noriyuki; Muramatsu, Fumiaki; Sakayori, Noriko; Kobayashi, Makio

doi:10.1016/s0887-8994(01)00369-1

Cited by 13 publications

(8 citation statements)

References 29 publications

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“…Double labeling with specific markers for neurons (anti-MAP2), astrocytes (anti-GFAP), and oligodendrocytes (anti-CNPase) confirmed that 4-HNE immunoreactivity was present in a large number of neurons and astrocytes in all brain regions examined, but relatively small numbers of oligodendrocytes were immunopositive for 4-HNE in the UCO fetal brain. Thus, after this brief asphyctic insult lipid peroxidation appears to occur preferentially in neurons and astrocytes, consistent to some extent with the previous study of human fetal brain that showed 4-HNE immunoreactivity only in astrocytes and neurons (18). …”

supporting

confidence: 91%

“…Nuclear and cytoplasmic 4-HNE staining in Purkinje cells has been observed previously in the human fetal cerebellum and attributed to a unique aspect of metabolism of the developing brain (18). The absence of any significant 4-HNE immunoreactivity in control fetal sheep brains in the present study suggests that 4-HNE is not normally produced in appreciable amounts by the developing brain, and, thus, oxidative (or other) stresses may have been present during the collection of this human fetal material.…”

Section: Discussionsupporting

confidence: 57%

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Lipid Peroxidation, Caspase-3 Immunoreactivity, and Pyknosis in Late-Gestation Fetal Sheep Brain after Umbilical Cord Occlusion

2004

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Umbilical cord occlusion (UCO), a known risk factor for perinatal brain damage, causes severe fetal asphyxia leading to oxidative stress, lipid peroxidation, and cell death. We have determined the effects of two 10-min UCO on the distribution of the lipid peroxidation marker 4-hydroxynonenal (4-HNE) and the activated form of the apoptosis marker caspase-3 in the brains of late-gestation fetal sheep. UCO caused asphyxia, hypertension, and bradycardia, but these parameters normalized 2 h after the occlusion. At postmortem, 48 h after the second UCO there were significantly higher numbers of 4-HNE-positive cells in all layers of the hippocampus and cerebellum, the parietal cortex, substantia nigra, caudate nucleus, putamen, and thalamus compared with control brains. 4-HNE immunoreactivity was also found in white matter tracts of the subcallosal bundle, external medullary lamina, reticular thalamic nucleus, and cerebellar fiber tracts only in UCO brains. Double-labeling identified these cells as predominantly neurons and astrocytes, with oligodendrocytes showing lower levels of 4-HNE immunoreactivity. After UCO, the number of caspase-3-immunoposotive cells was increased significantly in the hippocampal CA1, molecular layer and dentate gyrus, ventrolateral thalamic nucleus, substantia nigra, putamen, and cerebellar granular and molecular layers compared with controls. Double-labeling revealed caspase-3 immunoreactivity was mainly in neurons, and to lesser extent in astrocytes and oligodendrocytes. Pyknotic cell numbers were significantly increased in hippocampal CA1 and CA3, parietal cortex, caudate nucleus, putamen, and cerebellar Purkinje cells after UCO. These data indicate that brief asphyxia induces widespread lipid peroxidation involving all cell types of the fetal brain and apoptosis in both neurons and glia. Abbreviations UCO, umbilical cord occlusion 4-HNE, 4-hydroxynonenal ROS, reactive oxygen species TBARS, thiobarbituric acid-reactive substances PFA, paraformaldehyde NGS, normal goat serum GFAP, glial fibrillary acidic protein CNPase, 2', 3'-cyclic nucleotide 3'-phosphodiesterase MAP-2, microtubule associated protein Asphyxia and hypoxia are threats faced by the fetus in utero and are implicated in long-term postnatal sequelae such as mental retardation, seizure disorders and cerebral palsy (1). In particular, white matter injury is thought to result from insults that cause CNS inflammation and oxidative stress (2, 3). The brain is relatively deficient in oxidative defenses and highly susceptible to free radical damage (4). ROS alter the structure and function of proteins and DNA, and activate cysteine proteases (caspases), leading to apoptotic cell death (5). Hydroxyl radical, in particular, causes lipid peroxidation by rearranging double bonds in fatty acid side chains, and other radicals trigger the destruction of adjacent fatty acid molecules (4). Peroxidation of lipids leads to formation of cytotoxic reactive aldehydes, including malondialdehyde and 4-HNE (6). Cell membrane lipid composition makes so...

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supporting

confidence: 91%

Section: Discussionsupporting

confidence: 57%

Lipid Peroxidation, Caspase-3 Immunoreactivity, and Pyknosis in Late-Gestation Fetal Sheep Brain after Umbilical Cord Occlusion

2004

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“…Assessment is currently made by measuring advanced glycation end products from oxidation of proteins, carbohydrates and lipids in cytoplasm, nucleus and membranes [109] . The results of studies using these methods may help to determine the timing of the brain injury, since oxidation products appear to vary in relation to gestational age.…”

Section: Biomarkersmentioning

confidence: 99%

The Timing of Neonatal Brain Damage

Bracci¹,

Perrone²,

Buonocore³

2006

Neonatology

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Although neonatal morbidity and mortality are less than in the past, the risk of pre-natal and neonatal brain damage has not been eliminated. In order to optimize pre-natal, perinatal and neonatal care, it is necessary to detect factors responsible for brain damage and obtain information about their timing. Knowledge of the timing of asphyxia, infections and circulatory abnormalities would enable obstetricians and neonatologists to improve prevention in pre-term and full-term neonates. Cardiotocography has been criticized as being too indirect a sign of fetal condition and as having various technical pitfalls, though its reliability seems to be improved by association with pulse oximetry, fetal blood pH and electrocardiography. Neuroimaging is particularly useful to determine the timing of hypoxic-ischemic brain damage. Cranial ultrasound has been used to determine the type and evolution of brain damage. Magnetic resonance has also been used to detect antenatal, perinatal and neonatal abnormalities and timing on the basis of standardized assessment of brain maturation. Advances in the interpretation of neonatal electroencephalograms have also made this technique useful for determining the timing of brain lesions. Nucleated red blood cell count in cord blood has been recognized as an important indication of the timing of pre-natal hypoxia, and even abnormal lymphocyte and thrombocyte counts may be used to establish pre-natal asphyxia. Cord blood pH and base excess are well-known markers of fetal hypoxia, but are best combined with heart rate and blood pressure. Other markers of fetal and neonatal hypoxia useful for determining the timing of brain damage are assays of lactate and markers of oxidative stress in cord blood and neonatal blood. Cytokines in blood and amniotic fluid may indicate chorioamnionitis or post-natal infections. The determination of activin and protein S100 has also been proposed. Obstetricians and neonatologists can therefore now rely on various methods for monitoring the risk of brain damage in the antenatal and post-natal periods.

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“…Recent functional MRI studies of medication-naive children with ADHD have revealed inferior frontal and temporalparietal brain region dysfunctions related to learning, memory, attention and impulsivity problems [95][96][97]. Neural networks in brain regions mediating these executive processes are especially vulnerable to hypoglycemic coma, BBB compromise and hypoxic-ischemic crisis in children [98][99][100]. All of these events can play a role in the brain pathology following CM [90].…”

Section: Neuroanatomical Basis Of CM Cognitive Sequelaementioning

confidence: 99%

Pediatric Cerebral Malaria: A Scourge of Africa

et al. 2012

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Cerebral malaria, defined as an otherwise unexplained coma in a patient with Plasmodium falciparum parasitemia, affects up to 1 million people per year, the vast majority of them being children living in sub-Saharan Africa. Despite optimal treatment, this condition kills 15% of those affected and leaves 30% of survivors with neurologic sequelae. The clinical diagnosis is hampered by its poor specificity, but the presence or absence of a malarial retinopathy in cerebral malaria has proven to be important in the differentiation of underlying coma etiology. Both antimalarials and intense supportive care are necessary for optimal treatment. As of yet, clinical trials of adjunctive therapies have not improved the high rates of mortality and morbidity. Survivors are at high risk of neurologic sequelae including epilepsy, neurodisabilities and cognitive–behavioral problems. The neuroanatomic and functional bases of these sequelae are being elucidated. Although adjunctive therapy trials continue, the best hope for African children may lie in disease prevention. Strategies include bednets, chemoprophylaxis and vaccine development.

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Oxidative stress in the human fetal brain: an immunohistochemical study

Cited by 13 publications

References 29 publications

Lipid Peroxidation, Caspase-3 Immunoreactivity, and Pyknosis in Late-Gestation Fetal Sheep Brain after Umbilical Cord Occlusion

Lipid Peroxidation, Caspase-3 Immunoreactivity, and Pyknosis in Late-Gestation Fetal Sheep Brain after Umbilical Cord Occlusion

The Timing of Neonatal Brain Damage

Pediatric Cerebral Malaria: A Scourge of Africa

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