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Titolo:
Broad-spectrum and selective serine protease inhibitors prevent expressionof platelet-derived growth factor-BB and cerebral vasospasm after subarachnoid hemorrhage - Vasospasm caused by cisternal injection of recombinant platelet-derived growth factor-BB
Autore:
Zhang, Z; Nagata, I; Kikuchi, H; Xue, JH; Sakai, N; Sakai, H; Yanamoto, H;
Indirizzi:
Res Inst Natl Cardiovasc Ctr, Lab Cerebrovasc Disorders, Dept Neurosurg, Suita, Osaka 5658565, Japan Res Inst Natl Cardiovasc Ctr Suita Osaka Japan 5658565 aka 5658565, Japan Natl Cardiovasc Ctr, Osaka, Japan Natl Cardiovasc Ctr Osaka JapanNatl Cardiovasc Ctr, Osaka, Japan
Titolo Testata:
STROKE
fascicolo: 7, volume: 32, anno: 2001,
pagine: 1665 - 1672
SICI:
0039-2499(200107)32:7<1665:BASSPI>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
SMOOTH-MUSCLE CELLS; CEREBROSPINAL-FLUID; THROMBIN ACTIVITY; COMPLEMENT; FUT-175; ACTIVATION; ARTERIES; RAT; PROLIFERATION; MECHANISMS;
Keywords:
cerebral vasospasm; growth factors; subarachnoid hemorrhage;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Yanamoto, H Res Inst Natl Cardiovasc Ctr, Lab Cerebrovasc Disorders, Dept Neurosurg, 5-7-1 Fujishiro Dai, Suita, Osaka 5658565, Japan Res Inst Natl Cardiovasc Ctr 5-7-1 Fujishiro Dai Suita Osaka Japan 5658565
Citazione:
Z. Zhang et al., "Broad-spectrum and selective serine protease inhibitors prevent expressionof platelet-derived growth factor-BB and cerebral vasospasm after subarachnoid hemorrhage - Vasospasm caused by cisternal injection of recombinant platelet-derived growth factor-BB", STROKE, 32(7), 2001, pp. 1665-1672

Abstract

Background and Purpose - Plasma serine protease cascade, including the complement system and thrombin, is activated in the subarachnoid space during the acute phase after subarachnoid hemorrhage (SAH). To examine the effect of protease cascade-based inflammation and subsequent vascular repair in the development of cerebral vasospasm, we examined the effect of 2 synthetic serine protease inhibitors - FUT-175, an inhibitor of thrombin and the complement system, and argatroban, a selective inhibitor of thrombin - on the development of cerebral vasospasm in a rabbit SAH model. Methods - One hundred Japanese White male rabbits were used in the study. The SAH was simulated by a single injection of autologous arterial blood into the cisterna magna. To evaluate the development of cerebral vasospasm, the caliber of the basilar artery was measured on x-ray film before and at 2days after SAH. Nine groups of rabbits (n=6 each) were treated with continuous intravenous injection of FUT-175 (2.5, 5, 10, or 20 mg/d), argatroban (1.25, 2.5, or 5 mg/d), or the same amount of saline (vehicle) for 48 hours, starting 40 minutes after SAH. Two days after SAH, the expression of homodimer of platelet-derived growth factor-BE (PDGF-BB) in the basilar artery was examined with immunohistochemical techniques. In 20 normal rabbits, 5 mug of recombinant PDGF-BB or vehicle was injected into the cisterna magna, and the basilar arteries were examined on angiograms for 48 hours. Results-Significant differences were observed in the caliber of the basilar arteries between the vehicle group and the groups with the 3 larger dosesof FUT-175 (vehicle, 52 +/-5.0%; 5 mg, 79 +/-5.7%; 10 mg, 80 +/-2.5%; 20 mg, 80 +/-3.7%) and between the vehicle group and the groups with the 2 larger doses of argatroban (vehicle, 52 +/-6.4%; 2.5 mn, 81 +/-9.0%; 5 mg, 85 +/-4.1%) (P <0.05). In the histological examination, administration of effective doses of FUT-175 or argatroban suppressed the expression of PDGF-BB inthe endothelial and medial smooth muscle cell layers. Exogenous PDGF-BB caused delayed and prolonged vasoconstriction on normal basilar arteries. Conclusions - Activation of the serine protease cascade and/or thrombin after SAH was demonstrated to play an essential role in the development of cerebral vasospasm. The expression of PDGF-BB-like protein in the arterial walls correlated with the development of cerebral vasospasm. Elevated PDGF-BBlevel in the subarachnoid space was found to induce delayed and chronic vasoconstriction.

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Documento generato il 09/07/20 alle ore 17:27:10