Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
MECHANISMS OF SECONDARY BRAIN-DAMAGE IN GLOBAL AND FOCAL ISCHEMIA - ASPECULATIVE SYNTHESIS
Autore:
SIESJO BK; KATSURA KI; ZHAO Q; FOLBERGROVA J; PAHLMARK K; SIESJO P; SMITH ML;
Indirizzi:
UNIV LUND HOSP,EXPTL RES CTR,EXPTL BRAIN RES LAB S-22185 LUND SWEDEN
Titolo Testata:
Journal of neurotrauma
fascicolo: 5, volume: 12, anno: 1995,
pagine: 943 - 956
SICI:
0897-7151(1995)12:5<943:MOSBIG>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
MIDDLE CEREBRAL-ARTERY; TRANSIENT FOREBRAIN ISCHEMIA; PYRUVATE-DEHYDROGENASE ACTIVITY; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; NEURONAL DAMAGE; OXYGEN RADICALS; NITRIC-OXIDE; POLYMORPHONUCLEAR LEUKOCYTES; PREISCHEMIC HYPERGLYCEMIA;
Keywords:
SECONDARY BRAIN DAMAGE; ISCHEMIA; MITOCHONDRIAL FAILURE; MICROVASCULAR DYSFUNCTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
112
Recensione:
Indirizzi per estratti:
Citazione:
B.K. Siesjo et al., "MECHANISMS OF SECONDARY BRAIN-DAMAGE IN GLOBAL AND FOCAL ISCHEMIA - ASPECULATIVE SYNTHESIS", Journal of neurotrauma, 12(5), 1995, pp. 943-956

Abstract

The objective of this article is to amalgamate previous results into a speculative synthesis that sheds light on the causes of secondary brain damage following either global/forebrain or focal ischemia. The hypothesis is based on the well-founded assumption that the pathophysiology of the brain damage incurred by global or forebrain ischemia is different from that of focal ischemia. In the former, the ischemia is usually dense and of brief duration and, provided that reperfusion is adequate, cell damage is conspicuously delayed, mostly affecting selectively vulnerable neurons. In contrast, focal ischemia is either long-lasting or permanent, and it is usually less severe, particularly in theperifocal penumbral regions. The lesion is typically pan-necrotic (''infarction''), initially affecting the focus supplied by the occluded artery, later invading the penumbra zone. Available results allow a restatement of the calcium hypothesis of cell death. In global or forebrain ischemia, calcium influx through channels gated by voltage or glutamate receptors is envisaged to trigger reactions that limit the survival of neurons during reperfusion, leading to secondary neuronal deathafter hours or days of survival, It can be hypothesized that the initial insult leads to a sustained alteration of membrane calcium handling, resulting in slow, gradual calcium overload of mitochondria. Alternatively, a sustained perturbation of the intracellular signal transduction pathway leads to changes in transcription or translation, bereaving the cells of heat shock and stress proteins, of trophic factors, orof enzymes required for survival. However, with the possible exception of the gerbil, neither microvascular failure nor primary mitochondrial dysfunction is believed to be involved. In focal ischemia, similar reactions are probably triggered by calcium influx, whether this is sustained (the focus) or intermittent (the penumbra). However, these play a minor role in cell death since they are overridden by reactions producing mediators of rapidly developing secondary damage, affecting either microvessels or mitochondria. Very probably, some of these mediators are free radicals, or nitric oxide, or other reactive metabolites,emanating from lipid hydrolysis and arachidonic acid metabolism. During continuous ischemia, or during recirculation following 1-3 h of ischemia, these mediators activate adhesion molecules in endothelial cells or polymorphonuclear leucocytes, or oxidize key proteins. The resultis either failure of microcirculation (''capillary plugging''), or sustained mitochondrial failure. Since calcium influx is an initial event, agents reducing presynaptic depolarization and calcium entry through glutamate receptor-gated and other calcium channels have predictablya narrow therapeutic window; however, since spin trapping agents of the nitrone dass act many hours after the induction of focal ischemia, their therapeutic window is potentially very wide. This may be becauseexpression of mRNAs for adhesion molecules and their synthesis are relatively slow processes, and because the nitrones act on events that involve adhesion of leukocytes to the endothelial cells, with plugging of capillaries and postcapillary venules, and on the ensuing inflammatory response.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 15:19:22