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.
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: Lukas Andereggen; Volker Neuschmelting; Michael von Gunten; Hans Rudolf Widmer; Jukka Takala; Stephan M Jakob; Javier Fandino; Serge Marbacher Journal: J Vis Exp Date: 2014-10-02 Impact factor: 1.355
Authors: Davide M Croci; Stefan Wanderer; Fabio Strange; Basil E Grüter; Sivani Sivanrupan; Lukas Andereggen; Daniela Casoni; Michael von Gunten; Hans Rudolf Widmer; Stefano Di Santo; Javier Fandino; Luigi Mariani; Serge Marbacher Journal: Transl Stroke Res Date: 2021-01-06 Impact factor: 6.829
Authors: Davide Marco Croci; Stefan Wanderer; Fabio Strange; Basil E Grüter; Daniela Casoni; Sivani Sivanrupan; Hans Rudolf Widmer; Stefano Di Santo; Javier Fandino; Luigi Mariani; Serge Marbacher Journal: Brain Sci Date: 2019-09-24