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Titolo:
A selective cysteine protease inhibitor is non-toxic and cerebroprotectivein rats undergoing transient middle cerebral artery ischemia
Autore:
Seyfried, DM; Veyna, R; Han, YX; Li, KQ; Tang, NM; Betts, RL; Weinsheimer, S; Chopp, M; Anagli, J;
Indirizzi:
Henry Ford Hosp, Dept Neurosurg, Editorial Off, Detroit, MI 48202 USA Henry Ford Hosp Detroit MI USA 48202 Editorial Off, Detroit, MI 48202 USA Henry Ford Hosp, Dept Pathol, Detroit, MI 48202 USA Henry Ford Hosp Detroit MI USA 48202 , Dept Pathol, Detroit, MI 48202 USA Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA Henry Ford Hosp Detroit MI USA 48202 , Dept Neurol, Detroit, MI 48202 USA
Titolo Testata:
BRAIN RESEARCH
fascicolo: 1-2, volume: 901, anno: 2001,
pagine: 94 - 101
SICI:
0006-8993(20010518)901:1-2<94:ASCPII>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
DELAYED NEURONAL DEATH; CATHEPSIN-B; CALPAIN INHIBITORS; LYSOSOMAL-ENZYMES; HUMAN PLATELETS; BRAIN ISCHEMIA; CELL-DAMAGE; OCCLUSION; PROTEINASES; IMMUNOLOCALIZATION;
Keywords:
cathepsin B; cysteine protease; middle cerebral artery occlusion; focal cerebral ischemia; cathepsin L; protease inhibitor; rat;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Seyfried, DM Henry Ford Hosp, Dept Neurosurg, Editorial Off, 2799 W Grand Blvd, Detroit, MI 48202 USA Henry Ford Hosp 2799 W Grand Blvd Detroit MI USA 48202 02 USA
Citazione:
D.M. Seyfried et al., "A selective cysteine protease inhibitor is non-toxic and cerebroprotectivein rats undergoing transient middle cerebral artery ischemia", BRAIN RES, 901(1-2), 2001, pp. 94-101

Abstract

Ischemic neuronal injury mediated by cysteine proteases such as calpains and caspases has been demonstrated in various experimental models. Cathepsins B and L are also cysteine proteases which may contribute to neuronal death after ischemia. The authors measured in vitro and in vivo toxicity and post-ischemic cytoprotective effects of a cysteine protease inhibitor which does not block calpain or caspase but, rather, is relatively selective for cathepsins B and L. The compound belongs to the peptidyl-diazomethane family(cysteine protease inhibitor 1, termed CP-1). In vitro toxicity was measured using an assay of cell viability, and in vivo toxicity was measured by histological tissue analysis after infusion of CP-1 in rats. Two hours of middle cerebral artery (MCA) occlusion in rats was performed by the intravascular suture method. Immediately following reperfusion, intravenous infusionof CP-1 or vehicle was performed for 4 h at 0.9 ml/h. After a 7-day survival, the infarct volumes were measured. CP-1 was non-toxic to cultured glialcells to a local concentration of 200 muM, and relatively non-toxic to cultured endothelial cells at concentrations of 100-200 muM. No animal exhibited toxic effects at any of the doses used. Histologic comparisons revealed no signs of tissue toxicity. CP-1 significantly reduced hemispheric infarctvolume compared to control (37+/-8.2%) at concentrations of 10, 50, and 250 muM [22+/-15%, P = 0.008; 20+/-13%. P = 0.002; 23+/-15%, P = 0.022, respectively (mean+/-standard deviation: N = 7-10 per group)]. CP-1. at the concentration of 50 muM, improved the functional score of the animals, but did not significantly alter cerebral blood flow. This study supports the hypothesis that the lysosomal cathepsins B and/or L contribute to cerebral injuryafter focal ischemia with reperfusion. Cysteine protease inhibitors which are relatively selective for cathepsins B and L, but not the calpains or caspases, are effective at reducing infarct volume after intravenous post-ischemic administration. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/07/20 alle ore 09:11:34