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Titolo:
Selective antagonism of endothelin-A-receptors improves outcome in both head trauma and focal stroke in rat
Autore:
Barone, FC; Ohlstein, EH; Hunter, AJ; Campbell, CA; Hadingham, SH; Parsons, AA; Yang, Y; Shohami, E;
Indirizzi:
SmithKline Beecham Pharmaceut, Dept Cardiovasc Pharmacol, King Of Prussia,PA 19406 USA SmithKline Beecham Pharmaceut King Of Prussia PA USA 19406 a,PA 19406 USA SmithKline Beecham Pharmaceut, Dept Neurosci Res, Harlow CM19 5AD, Essex, England SmithKline Beecham Pharmaceut Harlow Essex England CM19 5AD ssex, England Hebrew Univ Jerusalem, Sch Pharm, IL-91120 Jerusalem, Israel Hebrew Univ Jerusalem Jerusalem Israel IL-91120 -91120 Jerusalem, Israel
Titolo Testata:
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
, volume: 36, anno: 2000, supplemento:, 1
pagine: S357 - S361
SICI:
0160-2446(2000)36:<S357:SAOEIO>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
CEREBRAL-ARTERY OCCLUSION; BRAIN-BARRIER PERMEABILITY; PHARMACOLOGICAL CHARACTERIZATION; ISCHEMIA; INJURY; MODEL; IMMUNOREACTIVITY; SB-209670; DAMAGE; MOTOR;
Keywords:
closed head injury (CHI); focal stroke; neuroprotection; neurological deficits; brain edema; brain injury; endothelin antagonists; SE 234551; SE 209670;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Barone, FC SmithKline Beecham Pharmaceut, Dept Cardiovasc Pharmacol, 709 Swedeland Rd,POB 1539, King Of Prussia, PA 19406 USA SmithKline Beecham Pharmaceut 709 Swedeland Rd,POB 1539 King Of Prussia PA USA 19406
Citazione:
F.C. Barone et al., "Selective antagonism of endothelin-A-receptors improves outcome in both head trauma and focal stroke in rat", J CARDIO PH, 36, 2000, pp. S357-S361

Abstract

Increased levels of endothelin (ET) have been demonstrated in the ischemicbrain, and ET receptor antagonism has been shown to improve outcome in cerebral ischemia. However, no previous work has been carried out evaluating the role of ET and its antagonism in brain trauma as compared to experimental stroke. In this study, we evaluated changes in brain ET levels following closed head injury (CHI) and the effects of SB 234551, an endothelin-A- (ETA) selective antagonist, and SE 209670, a mixed endothelin-A and -B- (ETA/ETB) antagonist, on outcome in CHI and focal stroke. Male Sabra rats were subjected to CHI (weight drop model). Male Sprague Dawley rats were subjectedto focal stroke (intraluminal suture model). Motor function(s) were assessed and immunoreactive ET (irET) and the degree of cerebral edema were measured for 24 h after CHI. Brain swelling (edema), neurological deficits and forebrain infarct volumes were measured 24 h after focal stroke. Antagonists(total doses of 7.5, 15, 30 or 60 mg/kg) were administered intravenously fur 6-24 h (beginning 15 min after injury). Control rats were infused with vehicle. CHI resulted in increased ET levels in the directly contused hemisphere at 12 and 24 h. In addition, SB 234551 significantly reduced neurological deficits (decreased 30%) and brain edema (decreased 40%) following CHI (p < 0.05 at 60 mg/kg dose). SE 209670 had no effects on CHI outcome. Focalstroke studies yielded similar results. SE 234551 reduced focal stroke-induced neurological deficits by 50%, brain swelling by 54% and the degree of infarction by 36% (p < 0.05 at 30 mg/kg). SE 209670 did not provide any neuroprotection in focal stroke. These data indicate that ET plays a significant role in the pathophysiology of CHI, and that selectively targeting ETA-receptors similarly in both CHI and stroke might be a therapeutic opportunity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 19:32:07