Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoxic encephalopathy during the late gestation and perinatal period occupies a large part as a cause of mentally and physically handicaps. An extensive study on the pathogenesis and pathophysiology of the hypoxic brain damage is, therefore, the matter of urgency to minimize the occurrence of handicapped children. The main factors and/or processes relating to hypoxic or hypoxic-ischemic brain damage are (1) structural and functional immaturity of the brain vascular system and (2) a metabolic cascade triggered by hypoxia. As the following metabolic cascade subsequent to hypoxia has been partly made clear; (a) disturbance of the energy metabolism, (b) excessive release of excitatory amino acids and subsequent activation of NMDA and K/Q receptors at the cell membrane, (c) collapse of the membrane ion pump, and (d) increase in turnover of membrane phospholipids.
 ...
PMID:[Pathogenesis of hypoxic encephalopathy during pre- and peri-natal periods]. 813 81

The distribution of [3H]glutamate binding sites was studied in a model of altered cerebellar development obtained by injecting methylazoxymethanol (MAM) in 5-day-old mice. In these mice, at the 25th postnatal day, cerebella were smaller than normal, stratification was normal except for the presence in some lobes of a thin ectopic granule cell layer in the middle of the molecular layer, the proportion of the distribution of [3H]glutamate binding sites between molecular and internal granule cell layers was maintained but site density of both quisqualate- and NMDA-sensitive types was increased in the two layers. In the molecular layer, this increase was uniform in spite of the presence of the ectopic cell layer. In the internal granular layer, the increase of quisqualate-sensitive and NMDA-sensitive [3H]glutamate binding sites is topographically segregated and the first corresponds to areas of lesser cellular density. These results show that MAM treatment induces persistent alterations of the cerebellar glutamatergic system, which consist of receptor over-expression, possibly due to deficit of innervation, reactive gliosis and immaturity of surviving granule cells.
 ...
PMID:Autoradiographic localization of [3H]-L-glutamate binding sites in a model of cerebellar granule cell ectopia generated by methylazoxymethanol treatment. 827 41

We determined the conditions (immaturity, species, anesthesia, receptor blockade selectivity) under which glutamate receptor blockade produces respiratory depression in mammals. In unrestrained 0- to 2-day-old neonate and adult mice and cats, ventilation was measured by the barometric method, before and after separate or sequential administration of a non-NMDA receptor antagonist, NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline, 2-200 mg kg(-1) in mice, 10-40 mg kg(-1) in cats), and a NMDA receptor antagonist, dizocilpine (3 mg kg(-1) in mice, 0.15-1.0 mg kg(-1) in cats). NBQX or dizocilpine alone did not decrease ventilation in awake adults, but NBQX strongly depressed ventilation in neonate awake mice and in adult anesthetized animals. Given together, dizocilpine and NBQX always profoundly depressed ventilation by producing a lethal apnea in neonate mice, and an apneustic pattern of breathing in adults of both species and in neonate cats. We conclude that blockade of either NMDA or non-NMDA receptors is innocuous in awake adults. The factors which may potentiate respiratory depression are (1) anesthesia, (2) immaturity, and (3) combined blockade of both receptors types. The mechanism of depression is species-dependent and age-dependent.
 ...
PMID:Respiratory effects of glutamate receptor antagonists in neonate and adult mammals. 965 39

The particularities in the medical treatment of children, especially those concerning premature infants, new-borns and babies, do not only stem from the immaturity of the organs (kidneys, liver etc.) but also from pharmacokinetic factors which are result of the immaturity of the brain. There are maturation deficits on all levels of transmission, from the nerve with electric transmission to the synapsis with neurotransmitter propagation, even though the whole system is basically laid out. The presented paper concerns itself mainly with the ontogenesis of the receptor-systems, a small part is dedicated to the question of myelination. Number and distribution of the receptors in premature or new-born infants and babies should not only be viewed in the context of the future function in mature humans (i.e. transmission and modification of information) - the receptors themselves are important factors in the maturing process of neuronal pathways, synapses and the differentiation of the neuronal cells themselves. Basically the number of receptors can change as follows: 1. Continuous increase until maturity, 2. Increase to a maximum during maturation with slight or stronger decrease after, 3. High initial number with following distinct decrease, 4. Even number throughout maturation, 5. Passing expression during maturation. The aim of this paper is to present an overview on the ontogenesis of opioid-, NMDA-, GABA-, dopamine-, acetylcholine- and serotoninreceptors. The data derived from animal and human-pharmacological experiments will be used to carefully conclude how the particularities of drug reactions of children (i.e. increased respiratory depression after opioid application in premature and newborn infants, higher incidence of paradox reactions to benzodiazepines etc.) can be explained.
 ...
PMID:[Ontogenesis of anesthesia-relevant receptors]. 1170 92

While studying the brain function of the human partial epilepsy gene, leucine-rich glioma-inactivated 1 (LGI1), a new mechanism of human epileptogenesis was revealed-persistent immaturity of glutamatergic circuitries. LGI1, a novel secreted protein, was found to be increased during the postnatal period; when glutamatergic synapses both downregulate their presynaptic vesicular release probability and reduce their postsynaptic NMDA-receptor subunit NR2B. During this same period, the dendritic arbor and spines are pruned and remodeled. Using bacterial artificial chromosome transgenic mouse techniques, excess wild-type LGI1 was shown to magnify these critical brain developmental events in the hippocampal dentate gyrus; while an epilepsy-associated, truncated, dominant-negative form of LGI1 blocked them. By contrast, the hippocampal dentate granule neuron GABAergic synapses and intrinsic excitability were unaltered. A role for LGI1 in downregulating glutamate synapse function was confirmed by germline gene deletion; this intervention also revealed a selective increase of glutamatergic synaptic transmission with unaltered GABAergic synapses and intrinsic excitability of hippocampal CA1 pyramidal neurons. Interestingly, the role of LGI1 in neurological disease was further expanded when a subset of patients with limbic encephalitis (an autoimmune disorder with memory loss in 100% and seizures in 80% of individuals) were discovered to carry autoantibodies to LGI1.
 ...
PMID:Arrested glutamatergic synapse development in human partial epilepsy. 2115 44