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)

The pattern of ischemia-induced cell death was examined with histochemical methods in the striatum of adult gerbils 4 and 7 days after transient forebrain ischemia. The results showed a massive loss of immunoreactivity to enkephalin and tachykinins, peptides present in striatal efferent neurons. In contrast, neurons expressing acetylcholinesterase activity, or choline acetyltransferase immunoreactivity, as well as neurons immunoreactive for somatostatin, were relatively preserved in areas of severe neuronal loss. The selective vulnerability of subpopulations of striatal neurons to transient ischemia in the adult is similar to that observed in the neonate and after local injections of agonists of N-methyl-D-aspartate receptors, but not of agonists of other glutamate receptor subtypes. It also presents striking similarities to the pattern of neuronal death observed in Huntington's disease. The results further support a role for overstimulation of a subtype of excitatory amino acid receptor in ischemia-induced cell death and show that the selective sparing of subpopulations of striatal interneurons after ischemic injury is not related to immaturity of these neurons but also occurs in the adult.
 ...
PMID:Ischemic damage in the striatum of adult gerbils: relative sparing of somatostatinergic and cholinergic interneurons contrasts with loss of efferent neurons. 197 9

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

To assess the influence of brain immaturity on the effects of oxygen deprivation and the participation of excitotoxicity, the consequences of a 6-h exposure to either hypoxia (95% N2/5% CO2) or 100 microM glutamate were studied in cultured fetal rat forebrain neurons taken at two maturational stages, i.e., 6 and 13 days in vitro. Cells were examined for their morphology, viability, energy metabolism reflected by 2-D-[3H]deoxyglucose uptake, and protein synthesis assessed by [3H]leucine incorporation. Apoptosis and necrosis were scored using the fluorescent dye 4,6-diamidino-2-phenylindole. Whereas 6-day-old neurons responded to a 6-h hypoxia by transient hypermetabolism, biphasic increase in protein synthesis, and cycloheximide-sensitive apoptotic death within 72 h postexposure, glutamate did not affect cell characteristics by the same time. In 13-day-old neurons, hypoxia induced both apoptosis (8.2%) and necrosis (22.3%). At this age, glutamate definitely reduced energy metabolism (26%) and protein synthesis (17%) by the end of exposure. The percentage of necrotic neurons reached 40.7%, but the rate of apoptosis was unchanged compared with controls. Therefore, excitotoxicity cannot account for hypoxia-induced injury in immature neurons, but its participation is suggested in older cells by the suppression of the necrotic component of hypoxia by glutamate receptor antagonists at 13 days.
 ...
PMID:Lack of correlation between the effects of transient exposure to glutamate and those of hypoxia/reoxygenation in immature neurons in vitro. 972 43

Cerebral white matter injury, characterised by loss of premyelinating oligodendrocytes (pre-OLs), is the most common form of injury to the preterm brain and is associated with a high risk of neurodevelopmental impairment. The unique cerebrovascular anatomy and physiology of the premature baby underlies the exquisite sensitivity of white matter to the abnormal milieu of preterm extrauterine life, in particular ischaemia and inflammation. These two upstream mechanisms can coexist and amplify their effects, leading to activation of two principal downstream mechanisms: excitotoxicity and free radical attack. Upstream mechanisms trigger generation of reactive oxygen and nitrogen species. The pre-OL is intrinsically vulnerable to free radical attack due to immaturity of antioxidant enzyme systems and iron accumulation. Ischaemia and inflammation trigger glutamate receptor-mediated injury leading to maturation-dependent cell death and loss of cellular processes. This review looks at recent evidence for pathogenetic mechanisms in white matter injury with emphasis on targets for prevention and treatment of injury.
 ...
PMID:Pathogenesis of cerebral white matter injury of prematurity. 1829 74