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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fetal ischemia or hypoxia can lead to cerebral palsy, mental retardation and epilepsy. We propose that the production of nitric oxide and oxygen radicals by neurons when ischemic or hypoxic brain is reperfused may contribute to cerebral injury. Ischemia will depolarize neuronal membranes causing the synaptic discharge of the excitatory neurotransmitter glutamate, which in turn opens the voltage-dependent, N-methyl-D-aspartic acid-specific glutamate receptor/ionophore, allowing calcium to accumulate in the neuron. Calcium in turn activates an oxygen-dependent neuronal nitric oxide synthetase, which oxidizes arginine to produce nitric oxide (.NO) when oxygen is readmitted to brain by reperfusion. Nitric oxide reacts with the oxygen radical superoxide (O2-), also produced by reperfusion, to form peroxynitrite (ONOO-). Peroxynitrite can diffuse for several micrometers before decomposing to form the powerful and cytotoxic oxidants hydroxyl radical and nitrogen dioxide. The hypothesis is consistent with available evidence on the protective action of glutamate antagonists and of oxygen radical scavengers for limiting cerebral infarction following focal ischemia.
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PMID:The double-edged role of nitric oxide in brain function and superoxide-mediated injury. 167 55

Cerebral hypoxia-ischemia remains a major cause of acute perinatal brain injury, leading ultimately to neurologic dysfunction manifest as cerebral palsy, mental retardation, and epilepsy. Research in experimental animals over the past 10 or more years has expanded greatly our understanding of the cellular and molecular events that occur during a hypoxic-ischemic insult to brain, and recent discoveries have suggested that metabolic perturbations arising in the recovery period after resuscitation contribute substantially to the nature and extent of neuronal destruction. The review focuses on those neurochemical processes responsible for the maintenance of cellular homeostasis and how these mechanisms fail in hypoxia-ischemia to culminate in brain damage. Knowledge of these critical events has opened new avenues of potential therapy for the fetus and newborn infant subjected to cerebral hypoxia-ischemia to prevent the serious delayed effects of perinatal brain injury.
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PMID:Experimental biology of cerebral hypoxia-ischemia: relation to perinatal brain damage. 197 36

The epidermal nevus syndrome (ENS) is a sporadic neurocutaneous disorder that consists of epidermal nevi and congenital anomalies involving the brain and other systems. From among over 60 patients with ENS presenting with neurologic manifestations, we identified 17 who had hemimegalencephaly based on pathologic or radiologic studies. Associated brain and neurologic abnormalities included gyral malformations in 12 of 12, mental retardation in 13 of 14, seizures in 16 of 17 (including 9 with infantile spasms), and contralateral hemiparesis in 7 of 12. All had ipsilateral epidermal nevi of the head, and several had ipsilateral facial hemihypertrophy. We concluded that these abnormalities comprise a recognizable neurologic variant of ENS that we believe represents the full expression of primary brain involvement. Several patients also had evidence of acquired brain lesions such as infarcts, atrophy, porencephaly, and calcifications, which are best explained by prior ischemia or hemorrhage. Given repeated observations of blood vessel anomalies in ENS patients, we hypothesize that underlying vascular dysplasia predisposes to these acquired lesions. The same cause may be invoked to explain the wide variety of neurologic symptoms reported in ENS patients without hemimegalencephaly. While the cause of ENS remains unknown, several observations suggest a somatic mutation.
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PMID:Epidermal nevus syndrome: a neurologic variant with hemimegalencephaly, gyral malformation, mental retardation, seizures, and facial hemihypertrophy. 199 73

Basic fibroblast growth factor (bFGF) has shown a neurotrophic effect in the neurons of several CNS areas. In vivo, it contributes to restore neurochemical and morphological deficits in different rodent models of brain damage, including rats with brain damage induced by hypoxia/ischemia when FGF was intramuscularly (i.m.) administered. Toxicological and immunological studies performed in rats, mice and volunteers showed no evidence of side-effects. Bovine FGF was i.m. administered in children with mental retardation caused by perinatal hypoxia, aged 1-15 years, at dosages of 0.4 or 0.28 microgram kg-1, once or twice a month, over 7-12 months. Group A [n = 12; 6 treated (T), 6 controls (Ct)], group B (n = 16; 8 T, 8 Ct) and group C (n = 67; 45 T, 22 Ct) were evaluated with the P. A. R. scale, the WISC-RM and the Gesell scale, respectively. Development increased significantly in treated children from groups A (P < 0.02) and C (P < 0.001), and IQ rose by more than 10 points (P < 0.001) in group B patients.
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PMID:Psychometric analysis in children with mental retardation due to perinatal hypoxia treated with fibroblast growth factor (FGF) and showing improvement in mental development. 812 97

Cortical heterotopia is defined as the misplacement of a group of neurons displaced to a precise localization in the neocortex and results from perturbed migration along the glial guide, either because of glial destruction or molecular anomalies. Heterotopic neurons are rarely dispersed but are rather grouped in nodules or bands. Heterotopic masses may lie in an ependymal or subcortical localization depending on whether they result from lack of migration or an arrested migration. Heterotopias can also occur in intra-cortical or extra-cortical localizations. The cause of heterotopia remains to be elucidated. Two genes situated on chromosome X have been implicated but non-genetic forms attributable to antenatal ischemia or toxic aggression during fetal development have also been observed. The presence of heterotopia is usually associated with epilepsy and sometimes with mental retardation. Seizures may be initiated within the heterotopic region then propagate via long projections to the neocortex which may also be malformed.
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PMID:[Cortical heterotopias: animal models and human disease]. 1009 50

The survival rate of very preterm, low birth weight infants (weighing less than 1500 g) is 85 per cent in the USA and is ever increasing, while 42 to 75 per cent of extremely premature infants (weighing 751-1000 g) survive. Of great concern is the lack of consistent decrease in neurological syndromes and associated visual impairments. Because of short gestations, these infants have not had time to accrue up to 80 per cent of magnesium normally present at term. These very preterm infants are at highest risk for cerebral hypoxia/ischemia (H/I), intracranial hemorrhage (ICH), periventricular leukomalacia (PVL) or cystic PVL (CPVL), and possible sequelae, cerebral palsy (CP) and mental retardation (MR). These syndromes are associated with damage to optic structures and the visual pathways which traverse the brain. Visual defects are common in surviving preterm infants. Increased levels of harmful neurochemical mediators that have been reported in these conditions include oxygen free radicals, excitatory amino acids, tumor necrosis factor-alpha (TNF-a), and thromboxane A2 (TXA2) which are aggravated in magnesium deficiency and may be ameliorated by magnesium. We review the published data concerning the effects of prenatal magnesium supplementation on ICH, CPVL, CP and MR and available reports concerning survival. Further considerations on the safety and efficacy of magnesium sulphate administration given prenatally to the preterm neonate await the outcome of three trials that are continuing for more than a year on three continents.
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PMID:The possible role of magnesium in protection of premature infants from neurological syndromes and visual impairments and a review of survival of magnesium-exposed premature infants. 1048 76

Twenty-nine high-risk preterm born children, from a cohort with cerebral blood flow (CBF) measurements in the first 2 d of life, were examined prospectively at the age of 5.5-7 y neurologically, neuropsychologically and by magnetic resonance imaging (MRI). They were compared to 57 control children in terms of neurology and neuropsychology. Abnormal MRI was found in 19 children. Low oxygen delivery to the brain was found in 63% of them, in contrast to 12.5% in those with normal MRI, indicating neonatal hypoxia-ischemia as an important factor. The MRI abnormalities were mainly periventricular lesions (n = 19), especially periventricular leucomalacia (PVL, n = 17). Three of the very preterm children had severe cerebellar atrophy in addition to relatively mild periventricular abnormalities. MRI showed specific morphological correlates for the major disabilities, e.g. spastic CP (involvement of motor tracts), mental retardation (bilateral extensive white matter reduction or cerebellar atrophy) and severe visual impairment (severe optic radiation involvement). A morphological correlate for minor disabilities, i.e. functional variations in motor performance or intelligence, was not found, with the exception that symptoms of attention deficit hyperactivity disorder were related to mild MRI abnormalities. This could mean that with respect to cognitive functions, mild or unilateral periventricular MRI lesions could be compensated. However, as among preterms without mental retardation (n = 19), IQ was generally and significantly lower than in the control group; other, more chronic pathogenetic factors, not detectable by MRI alone, may play a role.
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PMID:Brain lesions in preterms: origin, consequences and compensation. 1050 92

The 48,XXYY syndrome is a form of hypergonadotropic hypogonadism, characterized by tall statures, aggressive behavior, mental retardation, and stasis changes reflecting vascular insufficiency. We report a 25-year-old male with this syndrome showing a peripheral neuropathy and stasis dermatitis which were both reversed by administration of testosterone. Electrophysiologic studies, plethysmography, and thermography indicated that this treatment improved nerve conductivity and peripheral circulation. We postulate that in 48,XXYY syndrome a decrease in testosterone may result in peripheral neuropathy via nerve ischemia.
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PMID:Improvement of peripheral neuropathy by testosterone in a patient with 48,XXYY syndrome. 1112 5

Hypoxic-ischemic injury to the prenatal and perinatal brain is a major contributor to morbidity and mortality to infants, often leading to mental retardation, seizures, and cerebral palsy. The susceptibility of the immature CNS to hypoxia-ischemia is largely dependent on the temporal and regional status of critical developmental processes, as well as on the regulation of cerebral blood flow and metabolism. The molecular and biochemical mechanisms of acute injury to the neonatal brain in experimental rodent and murine models of hypoxic-ischemic and ischemic injury, including disturbances of intracellular homeostasis, role of glutamate receptors, free radicals and transitional ions, as well as the modifying role of gene expression to cell death/survival will be reviewed in this chapter.
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PMID:Molecular and biochemical mechanisms of perinatal brain injury. 1148 16

Cerebral hypoxia/ischemia of the newborn has a frequency of 4/1,000 births and remains a major cause of cerebral palsy, epilepsy, and mental retardation. Despite progress in understanding the pathogenesis of hypoxic-ischemic injury, the data are incomplete regarding the mechanisms leading to permanent brain injury. Here we tested the hypothesis that cerebral hypoxia/ischemia damages stem/progenitor cells in the subventricular zone (SVZ), resulting in a permanent depletion of oligodendrocytes. We used a widely accepted rat model and examined animals at recovery intervals ranging from 4 h to 3 weeks. Within hours after the hypoxic-ischemic insult 20% of the total cells were deleted from the SVZ. The residual damaged cells appeared necrotic. During 48 h of recovery deaths accumulated; however, these later deaths were predominantly apoptotic. Many apoptotic SVZ cells stained with a marker for immature oligodendrocytes. At 3 weeks survival, the SVZ was smaller and markedly less cellular, and it contained less than 1/4 the normal complement of neural stem cells. The corresponding subcortical white matter was dysmyelinated, relatively devoid of oligodendrocytes and enriched in astrocytes. We conclude that neural stem cells and oligodendrocyte progenitors in the SVZ are vulnerable to hypoxia/ischemia. Consequently, the developmental production of oligodendrocytes is compromised and regeneration of damaged white matter oligodendrocytes does not occur resulting in failed regeneration of CNS myelin in periventricular loci. The resulting dysgenesis of the brain that occurs subsequent to perinatal hypoxic/ischemic injury may contribute to the cognitive and motor dysfunction that results from asphyxia of the newborn.
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PMID:Hypoxia/ischemia depletes the rat perinatal subventricular zone of oligodendrocyte progenitors and neural stem cells. 1159 26


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