Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serial sections of cortical resection of 30 patients suffering from drug-resistant epilepsy were processed for parvalbumin and calbindin-D28k immunocytochemistry to determine local circuit neuron populations. Our findings indicate that there is not a simple mechanism to explain neocortical epileptic foci. On the basis of the present results it can be suggested that: (1) reduced percentage of local circuit neurons in the vicinity of neoplasms may account for a decreased intracortical inhibition. (2) Abnormal morphology and distribution of local circuit neurons may result in abnormal cortical inhibition in patients with focal cortical dysplasia, and, probably, in other focal migrational disorders, including neuronal nests in the white matter. (3) Increased percentages of immunoreactive local circuit neurons and fibers in focal neocortical necrosis (cavernous angiomas), diffuse hypoxic encephalopathy, and hippocampus in patients with temporal lobe epilepsy due to mesial sclerosis, may play a role in epilepsy. These neurons can be activated by reduced excitatory inputs, or they may establish abnormal synaptic contacts with other inhibitory neurons. (4) Lack of consistent morphologic abnormalities in the neocortex of patients with temporal lobe epilepsy, and in patients with cryptogenetic frontal lobe epilepsy, suggests that electrically abnormal neocortical foci in these cases are probably epiphenomena.
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PMID:Parvalbumin and calbindin-D28k immunocytochemistry in human neocortical epileptic foci. 806 11

We have immunohistochemically analyzed the marbled state in 8 cases of perinatal hypoxic ischemic encephalopathy and 4 cases of infantile hypoxic encephalopathy, using antibodies against calbindin-D28k (CaBD), glial fibrillary acidic protein (GFAP), methionine-enkephalin (MEnk), myelin basic protein (MBP), neurofilament (NF), parvalbumin (PV), substance-P (SuP) and synaptophysin (SP). The marbled state was found in the thalamus in 11 cases, whose age at death was over 10 years. Four cases demonstrated the marbled state in the cerebral cortex, in addition to the striatum and/or the thalamus. The abnormally myelinated fibers in the marbled state were stained with both Kluver-Barrera and Holzer stainings; however, they were partly immunopositive for MBP and completely immunonegative for GFAP, CaBD, MEnk, PV, SuP and SP, although some of the neurons and/or fibers showed immunoreactivities for those calcium-binding proteins and/or neurotransmitters. The axons were visualized in the abnormally myelinated fibers by Bodian staining and/or anti-NF immunostainings in the cerebral cortex and striatum but not in the thalamus. GFAP-positive astrocytes did not show any continuity with the abnormally myelinated fibers. These histological features were seen in the cerebral cortex, striatum and thalamus. Difference of the etiology did not affect the histological features with the exception of anti-PV staining, in which PV-immunopositive neurons were observed only in aged subjects with infantile hypoxic encephalopathy, and seemed to be more severely affected by hypoxic stress during the perinatal period than the early infantile period. These data suggest that the site of lesion or the length of survival period after brain injury might influence the formation of the marbled state rather than the etiology. And the direct relationship between the abnormally myelinated fiber and astrocytic process was not verified.
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PMID:Immunohistochemical evaluation of the marbled state in childhood hypoxic encephalopathy. 1048 83

Tyrosine hydroxylase (TH) deficiency is an inborn error of dopamine synthesis. Two clinical phenotypes have been described. The THD "B" phenotype produces a severe encephalopathy of early-onset with sub-optimal L-Dopa response, whereas the "A" phenotype has a better L-Dopa response and outcome. The objective of the study is to describe the expression of key synaptic proteins and neurodevelopmental markers in a fetal brain of THD "B" phenotype. The brain of a 16-week-old miscarried human fetus was dissected in different brain areas and frozen until the analysis. TH gene study revealed the p.R328W/p.T399M mutations, the same mutations that produced a B phenotype in her sister. After protein extraction, western blot analyses were performed to assess protein expression. The results were compared to an age-matched control. We observed a decreased expression in TH and in other dopaminergic proteins, such as VMAT 1 and 2 and dopamine receptors, especially D2DR. GABAergic and glutamatergic proteins such as GABA VT, NMDAR1 and calbindin were also altered. Developmental markers for synapses, axons and dendrites were decreased whereas markers of neuronal volume were preserved. Although this is an isolated case, this brain sample is unique and corresponds to the first reported study of a THD brain. It provides interesting information about the influence of dopamine as a regulator of other neurotransmitter systems, brain development and movement disorders with origin at the embryological state. This study could also contribute to a better understanding of the pathophysiology of THD at early fetal stages.
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PMID:Study of a fetal brain affected by a severe form of tyrosine hydroxylase deficiency, a rare cause of early parkinsonism. 2668 76

Prematurity is associated with significantly increased risk of neurobehavioral pathologies, including autism and schizophrenia. A common feature of these psychiatric disorders is prefrontal cortex (PFC) inhibitory circuit disruption due to GABAergic interneuron alteration. Cortical interneurons are generated and migrate throughout late gestation and early infancy, making them highly susceptible to perinatal insults such as preterm birth. Term and preterm PFC pathology specimens were assessed using immunohistochemical markers for interneurons. Based on the changes seen, a new preterm encephalopathy mouse model was developed to produce similar PFC interneuron loss. Maternal immune activation (MIA; modeling chorioamnionitis, associated with 85% of extremely preterm births) was combined with chronic sublethal hypoxia (CSH; modeling preterm respiratory failure), with offspring of both sexes assessed anatomically, molecularly and neurobehaviorally. In the PFC examined from the human preterm samples compared to matched term samples at corrected age, a decrease in somatostatin (SST) and calbindin (CLB) interneurons was seen in upper cortical layers. This pattern of interneuron loss in upper cortical layers was mimicked in the mouse PFC following the combination of MIA and CSH, but not after either insult alone. This persistent interneuron loss is associated with postnatal microglial activation that occurs during CSH only after MIA. The combined insults lead to long-term neurobehavioral deficits which parallel human psychopathologies that may be seen after extremely preterm birth. This new preclinical model supports a paradigm in which specific cellular alterations seen in preterm encephalopathy can be linked with a risk of neuropsychiatric sequela. Specific interneuron subtypes may provide therapeutic targets to prevent or ameliorate these neurodevelopmental risks.
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PMID:Impaired Interneuron Development in a Novel Model of Neonatal Brain Injury. 3080 88