Document Detail


Platelet-derived growth factor-induced severe and chronic vasoconstriction of cerebral arteries: proposed growth factor explanation of cerebral vasospasm.
MedLine Citation:
PMID:  20305494     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: After subarachnoid hemorrhage (SAH), platelet-derived growth factor-BB (PDGF-BB) is secreted in and around the cerebral arteries. To clarify the role of PDGF-BB in the development of vasospasm after SAH, we determined whether PDGF-BB alone can cause long-lasting vasoconstriction of a severity similar to that of vasospasm. In addition, the anti-vasospastic effect of trapidil, an antagonist of PDGF-BB function, was investigated. METHODS: We infused recombinant PDGF-BB (10 microg/mL saline as the vehicle) (n = 14) into the subarachnoid space of rabbits and analyzed alterations in the caliber of the basilar artery using repeated angiography. To study the role of PDGF-BB on the development of vasospasm, trapidil was administered continuously starting 1 hour after SAH, on day 0 (0.63-1.25 mg/kg /h or vehicle) for 47 hours (n = 24), or after the full development of cerebral vasospasm on day 2 (3.0 mg/kg/h or vehicle) for 0.5 hours (n = 17), and alterations in the caliber of the basilar artery were monitored. RESULTS: PDGF-BB caused long-lasting vasoconstriction, with maximum constriction of 56% (P < .001) of the control value (= 100%) on day 2, resembling vasospasm seen after SAH. Prolonged administration of intravenous trapidil, starting soon after SAH, prevented the development of vasospasm in a dose-dependent manner (P < .05, .01, or .001). Intravenous or intra-arterial administration of trapidil significantly dilated vasospasm (P < .01) on day 2, at least transiently. CONCLUSION: PDGF-BB, a growth factor synthesized in the subarachnoid space after SAH, can cause severe and long-lasting vasoconstriction. Significant prevention and resolution of vasospasm can be achieved by the PDGF-BB antagonist trapidil. We propose that excessive production of PDGF-BB, essentially aiming to repair injured arteries, causes cerebral vasospasm. Although the half-life of trapidil in serum may be shorter than that of PDGFG-BB-derived spasmogenic signaling, trapidil is a candidate drug for constructing a new therapeutic modality for preventing and resolving vasospasm.
Authors:
Zhi-Wen Zhang; Hiroji Yanamoto; Izumi Nagata; Susumu Miyamoto; Yukako Nakajo; Jing-Hui Xue; Koji Iihara; Haruhiko Kikuchi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neurosurgery     Volume:  66     ISSN:  1524-4040     ISO Abbreviation:  Neurosurgery     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-22     Completed Date:  2010-06-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7802914     Medline TA:  Neurosurgery     Country:  United States    
Other Details:
Languages:  eng     Pagination:  728-35; discussion 735     Citation Subset:  IM    
Affiliation:
Laboratory for Cerebrovascular Disorders, Research Institute of National Cardiovascular Center, Suita, Osaka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cerebral Angiography / methods
Cerebral Arteries / drug effects*
Disease Models, Animal
Dose-Response Relationship, Drug
Male
Platelet-Derived Growth Factor / adverse effects*,  metabolism*
Rabbits
Subarachnoid Hemorrhage / chemically induced,  physiopathology*
Time Factors
Trapidil / adverse effects
Vasoconstriction / drug effects*
Vasodilator Agents / adverse effects
Vasospasm, Intracranial / etiology*
Chemical
Reg. No./Substance:
0/Platelet-Derived Growth Factor; 0/Vasodilator Agents; 15421-84-8/Trapidil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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