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Titolo:
Cellular mechanisms of hypoxic injury in the developing brain
Autore:
Mishra, OP; Delivoria-Papadopoulos, M;
Indirizzi:
MCP Hahneman Sch Med, Dept Pediat, Philadelphia, PA USA MCP Hahneman Sch Med Philadelphia PA USA pt Pediat, Philadelphia, PA USA St Christophers Hosp Children, Philadelphia, PA USA St Christophers Hosp Children Philadelphia PA USA , Philadelphia, PA USA
Titolo Testata:
BRAIN RESEARCH BULLETIN
fascicolo: 3, volume: 48, anno: 1999,
pagine: 233 - 238
SICI:
0361-9230(199902)48:3<233:CMOHII>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
GUINEA-PIG BRAIN; NUCLEAR-ENVELOPE BREAKDOWN; EXCITATORY AMINO-ACIDS; NEWBORN PIGLET; NMDA RECEPTOR; FREE-RADICALS; LIPID-PEROXIDATION; MATERNAL HYPOXIA; CEREBRAL HYPOXIA; CALCIUM;
Keywords:
hypoxia; brain; development; oxygen; free radicals; peroxidation; Ca++; NMDA receptor; programmed cell death;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Mishra, OP Penn,Hosp, Coll Med, Dept Pediat, Ann Preston Hall,2nd Floor,3300 Henry Ave Penn Hosp Ann Preston Hall,2nd Floor,3300 Henry Ave Philadelphia PA USA 19129
Citazione:
O.P. Mishra e M. Delivoria-Papadopoulos, "Cellular mechanisms of hypoxic injury in the developing brain", BRAIN RES B, 48(3), 1999, pp. 233-238

Abstract

The susceptibility of the developing brain to hypoxia should depend on thelipid composition of the brain cell membrane; the rate of lipid peroxidation; the presence of antioxidant defenses; and the development and modulation of the excitatory neurotransmitter receptors such as the N-methyl-D-aspartate (NMDA) receptor, the intracellular Ca++ and intranuclear Ca++-dependent mechanisms. In addition to the developmental status of these cellular components, the response of these potential mechanisms to hypoxia determines the fate of the hypoxic brain cell in the developing brain. In the fetal guinea pig and newborn piglet models, studies have demonstrated that brain tissue hypoxia results in brain cell membrane damage as evidenced by increasedmembrane lipid peroxidation and decreased Na+,K+-ATPase activity. Using electron spin resonance spectroscopy of alpha-phenyl-N-tert-butyl-nitrone spin-adducts, studies from our laboratory have demonstrated that tissue hypoxia results in increased free radical generation in the cortex of fetal guinea pigs and newborn piglets. We have also shown that brain tissue hypoxia modifies the N-methyl-D-aspartate receptor-ion channel, recognition and modulatory sites. Furthermore, a higher increase in NMDA receptor agonist-dependent Ca++ in synaptosomes of hypoxic as compared to normoxic fetuses was demonstrated. The increase in intracellular Ca++ may activate several enzymatic pathways such as phospholipase A(2) and metabolism of arachidonic acid bycyclooxygenase and lipoxygenase, conversion of xanthine dehydrogenase to xanthine oxidase by proteases and activation of nitric oxide synthase. Usingspecific inhibitors of each of these enzymes such as cyclooxygenase (indomethacin), lipoxygenase (nordihydroguaiaretic acid), xanthine oxidase (allopurinol) and nitric oxide synthase (N-nitro-L-arginine), studies have shown that these enzyme reactions result in oxygen free radical generation, membrane lipid peroxidation and cell membrane dysfunction in the hypoxic brain. We suggest that, during hypoxia, the increased intracellular Ca++ may lead to an increased intranuclear Ca++ concentration and alter nuclear events including transcription of specific genes responsible for programmed cell death. In view of the developmental studies presented, the susceptibility of the fetal brain to hypoxia appears to increase with brain development as gestation approaches term. (C) 1999 Elsevier Science Inc.

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Documento generato il 29/03/20 alle ore 17:48:47