Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present knowledge on periventricular leucomalacia is reviewed. Its incidence is about 10% in preterms infants < 32 gestational weeks. By careful ultrasonographic scanning four stages can be distinguished: Prolonged flares, resolution, cystic leucomalacia, ventriculomegaly. Periventricular leucomalacia (PVL) is much more correlated with later neurologic impairment than intraventricular haemorrhage (apart from grade IV). PVL is caused by ischemia of the periventricular white matter mainly due to arterial hypotension and disturbed regulation of cerebral blood flow. The interactions between blood pressure, pCO2, pO2 and cerebral blood flow are complex and poorly understood. Regarding the clinical management it seems important to avoid hypotension, fluctuating pCO2 and hypoxemia/anemia in order to prevent white matter ischemia. Research should be focussed on the development of monitoring methods (doppler sonography, near infrared spectroscopy, time compressed electroencephalography), which allow to detect ischemic events to prevent neurologic impairment in about 1000 preterm infants per year in Germany.
 ...
PMID:[Periventricular leukomalacia]. 841 33

Periventricular leukomalacia is an infrequent but severe lesion in the premature neonate. The presence of positive rolandic sharp waves (PRSW) on the electroencephalogram, regardless of their morphology, is a reliable marker of periventricular ischemia, justifying systematic EEG monitoring during the first three weeks of life for infants born at less than 34 weeks of amenorrhea. A retrospective study of 32 premature neonates with extensive cavitary periventricular leukomalacia confirmed the early occurrence of positive rolandic sharp waves in 84% of premature newborns. The mean rate of PRSW was 1.54/min, but showed great variability. In C(Z), these sharp waves which were more frequent or isolated in one case, had the same value as those recorded in C3 or C4. Four neonates had no PRSW, but late periventricular leukomalacia was diagnosed at one month of age. As all these premature infants were born before 29 weeks of amenorrhea, longer EEG monitoring was justified. The prognosis was very poor: 17 newborns died, 11 had motor, sensory and intellectual impairment, and three had motor lesions.
 ...
PMID:[Severe periventricular leukomalacia: characteristic electroencephalographic features]. 876 23

Periventricular leukomalacia in the premature infant is a lesion of cerebral white matter with its greatest period of risk when white matter is immature, that is, when oligodendrocyte precursors are proliferating and differentiating, and before myelin sheaths are actively synthesized. Although the pathogenesis of perinatal cerebral white matter damage involves multiple factors, the correlation of the timing of the lesion with dominance of oligodendrocyte precursors in cerebral white matter suggests that intrinsic factors related to oligodendrocyte precursors are critical. Ischemia and infection have both been implicated as causes of perinatal white matter damage. Major mechanisms underlying oligodendrocyte injury in ischemia include glutamate toxicity, free-radical injury, and cytokine damage mediated by macrophages accompanying ischemia-induced inflammation. Factors related to a vulnerability of immature oligodendrocytes to ischemia potentially include a developmental lack of antioxidant enzymes to mediate oxidative stress. Cytokine-mediated injury to oligodendrocytes is also potentially important. A complete understanding of the role of immature white matter in the pathogenesis of periventricular leukomalacia is essential for developing strategies to prevent it.
 ...
PMID:Human oligodendroglial development: relationship to periventricular leukomalacia. 977 76

Periventricular leukomalacia (PVL), the principal form of brain injury in the premature infant, is characterized by overt focal necrotic lesions in periventricular white matter and less prominent, more diffuse cerebral white matter injury. The early detection of the latter, diffuse component of PVL is not consistently possible with conventional brain imaging techniques. We demonstrate the early detection of the diffuse component of PVL by diffusion-weighted magnetic resonance imaging (DWI). In a premature infant with no definite cerebral abnormality detectable by cranial ultrasonography or conventional magnetic resonance imaging, DWI showed a striking bilateral decrease in water diffusion in cerebral white matter. The DWI abnormality (ie, decreased apparent diffusion coefficient) was similar to that observed with acute cerebral ischemic lesions in adults. At 10 weeks of age, conventional magnetic resonance imaging and ultrasonography showed striking changes consistent with PVL, including the presence of small cysts. The observations indicate the importance of DWI in the early identification of the diffuse component of PVL and also perhaps the role of ischemia in the pathogenesis of the lesion.
 ...
PMID:Early detection of periventricular leukomalacia by diffusion-weighted magnetic resonance imaging techniques. 1070 Jul 8

The relationship between MR patterns of brain damage and type or timing of perinatal hypoxia-ischemia was studied. MR images of 104 children with evidence of bilateral posthypoxic-ischemic brain damage and neonatal records were reviewed. Three different MR patterns were found. Periventricular leukomalacia occurred in 73 children, in 82% after a history of subacute or chronic hypoxia-ischemia, in 71% after preterm birth. Predominant lesions of basal ganglia and thalamus occurred in 21 children, in 95% preceded by acute profound asphyxia, in 85% after term birth. Multicystic encephalopathy occurred in 10 infants, in 70% preceded by mild signs of hypoxia-ischemia, followed by an unexpectedly severe encephalopathy, in 60% after term birth. Statistical analysis showed that the patterns of injury were primarily related to the type of hypoxia-ischemia. We conclude that the type of hypoxia-ischemia, rather than the postconceptional age at occurrence determines the pattern of brain injury.
 ...
PMID:MR patterns of hypoxic-ischemic brain damage after prenatal, perinatal or postnatal asphyxia. 1096 99

Brain injury in the premature infant is a problem of enormous importance. Periventricular leukomalacia (PVL) is the major neuropathologic form of this brain injury and underlies most of the neurologic morbidity encountered in survivors of premature birth. Prevention of PVL now seems ultimately achievable because of recent neurobiologic insights into pathogenesis. The pathogenesis of this lesion relates to three major interacting factors. The first two of these, an incomplete state of development of the vascular supply to the cerebral white matter, and a maturation-dependent impairment in regulation of cerebral blood flow underlie a propensity for ischemic injury to cerebral white matter. The third major pathogenetic factor is the maturation-dependent vulnerability of the oligodendroglial (OL) precursor cell that represents the major cellular target in PVL. Recent neurobiologic studies show that these cells are exquisitely vulnerable to attack by free radicals, known to be generated in abundance with ischemia-reperfusion. This vulnerability of OLs is maturation-dependent, with the OL precursor cell highly vulnerable and the mature OL resistant, and appears to relate to a developmental window characterized by a combination of deficient antioxidant defenses and active acquisition of iron during OL differentiation. The result is generation of deadly reactive oxygen species and apoptotic OL death. Important contributory factors in pathogenesis interact with this central theme of vulnerability to free radical attack. Thus, the increased likelihood of PVL in the presence of intraventricular hemorrhage could relate to increases in local iron concentrations derived from the hemorrhage. The important contributory role of maternal/fetal infection or inflammation and cytokines in the pathogenesis of PVL could be related to effects on the cerebral vasculature and cerebral hemodynamics, to generation of reactive oxygen species, or to direct toxic effects on vulnerable OL precursors. A key role for elevations in extracellular glutamate, caused by ischemia-reperfusion, is suggested by demonstrations that glutamate causes toxicity to OL precursors by both nonreceptor- and receptor-mediated mechanisms. The former involves an exacerbation of the impairment in antioxidant defenses, and the latter, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptor-mediated cell death. Most importantly, these new insights into the pathogenesis of PVL suggest potential preventive interventions. These include avoidance of cerebral ischemia by detection of infants with impaired cerebrovascular autoregulation, e.g. through the use of in vivo near-infrared spectroscopy, the use of free radical scavengers to prevent toxicity by reactive oxygen species, the administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptor antagonists to prevent glutamate-mediated injury, or the use of maternal antibiotics or anticytokine agents to prevent toxicity from maternal/fetal infection or inflammation and cytokines.
 ...
PMID:Neurobiology of periventricular leukomalacia in the premature infant. 1164 46

The immature visual system is vulnerable to adverse events. Periventricular leukomalacia (PVL), an end-stage lesion after hypoxia-ischemia at gestational age 24-34 weeks affecting the visual radiation, has become a principal cause of visual impairment in children. Cerebral visual dysfunction caused by PVL is characterized by delayed visual maturation, subnormal visual acuity, crowding, visual field defects, and visual perceptual-cognitive problems. Magnetic resonance imaging is the method of choice for diagnosing this brain lesion, which is associated with optic disk abnormalities, strabismus, nystagmus, and deficient visually guided eye movements. Children with PVL may present to the ophthalmologist within a clinical spectrum from severe visual impairment in combination with cerebral palsy to only early-onset esotropia, normal intellectual level and no cerebral palsy. Optimal educational and habilitational strategies need to be developed to meet the needs for this group of children.
 ...
PMID:Visual and perceptual characteristics, ocular motility and strabismus in children with periventricular leukomalacia. 1222 99

Periventricular leukomalacia (PVL), the major lesion underlying cerebral palsy in survivors of prematurity, is characterized by focal periventricular necrosis and diffuse gliosis of immature cerebral white matter. Causal roles have been ascribed to hypoxiaischemia and maternal-fetal infection, leading to cytokine responses, inflammation, and oligodendrocyte cell death. Because interferon-gamma (IFN-gamma) is directly toxic to immature oligodendrocytes, we tested the hypothesis that it is expressed in PVL (N = 13) compared to age-adjusted controls (N = 31) using immunocytochemistry. In PVL, IFN-gamma immunopositive macrophages were clustered in necrotic foci, and IFN-gamma immunopositive reactive astrocytes were present throughout the surrounding white matter (WM). The difference in the number of IFN-gamma immunopositive glial cells/high power field (IFN-gamma score, Grades 0-3) between PVL cases (age-adjusted mean 2.59+/-0.25) and controls (age-adjusted mean 1.39+/-0.16) was significant (p<0.001). In the gliotic WM, the IFN-gamma score correlated with markers for lipid peroxidation, but not nitrative stress. A subset of premyelinating (04+) oligodendrocytes expressed IFN-gamma receptors in PVL and control cases, indicating that these cells are vulnerable to IFN-gamma toxicity via receptor-mediated interactions. In PVL, IFN-gamma produced by macrophages and reactive astrocytes may play a role in cytokine-induced toxicity to premyelinating oligodendrocytes as part of a cytokine response stimulated by ischemia and/or infection.
 ...
PMID:Interferon-gamma expression in periventricular leukomalacia in the human brain. 1577 42

Periventricular leukomalacia (PVL) involves free radical injury to developing oligodendrocytes (OLs), resulting from ischemia/reperfusion, particularly between 24 and 32 gestational weeks. Using immunocytochemistry and Western blots, we tested the hypothesis that this vulnerability to free radical toxicity results, in part, from developmental lack of superoxide dismutases (SOD)-1 and -2, catalase, and glutathione peroxidase (GPx) in the telencephalic white matter of the human fetus. During the period of greatest PVL risk and through term (> or = 37 weeks), expression of both SODs (for conversion of O2- to H2O2) significantly lagged behind that of catalase and GPx (for breakdown of H2O2), which, in contrast, superseded adult levels by 30 gestational weeks. Our data indicate that a developmental "mismatch" in the sequential antioxidant enzyme cascade likely contributes to the vulnerability to free radical toxicity of the immature cerebral white matter, which is "unprepared" for the transition from a hypoxic intrauterine to an oxygen-rich postnatal environment. All enzymes, localized to astrocytes and OLs, had higher-than-adult expression at 2 to 5 postnatal months (peak of myelin sheath synthesis), suggesting an adaptive mechanism to protect against lipid peroxidation during myelin sheath (lipid) synthesis. The previously unrecognized dissociation between the expression of the SODs and that of catalase and GPx in the fetal period has potential implications for future antioxidant therapy in PVL.
 ...
PMID:Developmental lag in superoxide dismutases relative to other antioxidant enzymes in premyelinated human telencephalic white matter. 1545 97

Periventricular leukomalacia (PVL) is the major substrate of cerebral palsy in survivors of prematurity. Its pathogenesis is complex and likely involves ischemia/reperfusion in the critically ill premature infant, with impaired regulation of cerebral blood flow, as well as inflammatory mechanisms associated with maternal and/or fetal infection. During the peak period of vulnerability for PVL, developing oligodendrocytes (OLs) predominate in the white matter. We hypothesize that free radical injury to the developing OLs underlies, in part, the pathogenesis of PVL and the hypomyelination seen in long-term survivors. In human PVL, free radical injury is supported by evidence of oxidative and nitrative stress with markers to lipid peroxidation and nitrotyrosine, respectively. Evidence in normal human cerebral white matter suggests an underlying vulnerability of the premature infant to free radical injury resulting from a developmental mismatch of antioxidant enzymes (AOE) and subsequent imbalance in oxidant metabolism. In vitro studies using rodent OLs suggest that maturational susceptibility to reactive oxygen species is dependent, not only on levels of individual AOE, but also on specific interactions between these enzymes. Rodent in vitro data further suggest 2 mechanisms of nitric oxide damage: one involving the direct effect of nitric oxide on OL mitochondrial integrity and function, and the other involving an activation of microglia and subsequent release of reactive nitrogen species. The latter mechanism, while important in rodent studies, remains to be determined in the pathogenesis of human PVL. These observations together expand our knowledge of the role that free radical injury plays in the pathogenesis of PVL, and may contribute to the eventual development of therapeutic strategies to alleviate the burden of oxidative and nitrative injury in the premature infant at risk for PVL.
 ...
PMID:Oxidative and nitrative injury in periventricular leukomalacia: a review. 1619 89


1 2 3 Next >>