Inhibition of poly(ADP-ribose) polymerase attenuates cerebral vasospasm after subarachnoid hemorrhage in rabbits

Motoyoshi Satoh, Isao Date, Masaaki Nakajima, Kenji Takahashi, Keiichi Iseda, Takashi Tamiya, Takashi Ohmoto, Yoshifumi Ninomiya, Shoji Asari

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Background and Purpose - Poly(ADP-ribose) polymerase (PARP) is important in modulating inflammation, which has been implicated in cerebral vasospasm after subarachnoid hemorrhage (SAH). We investigated the role of PARP in vasospasm using 3-aminobenzamide (3-AB), a PARP inhibitor, in a rabbit model. Methods - Twenty-four New Zealand White rabbits were divided into 4 groups: (1) no treatment (control group, n=6); (2) blood injection without pretreatment (SAH-only group, n=6); (3) blood injection with pretreatment by vehicle (SAH+vehicle group, n=6); and (4) blood injection with pretreatment by 3-AB (SAH+3-AB group, n=6). We used the single-hemorrhage model of SAH, injecting autologous arterial blood into the cisterna magna. Angiography was performed before (baseline) and after (day 2) SAH, and the diameter of the basilar artery (BA) was measured. Animals were euthanatized after the second angiogram. After perfusion and fixation, the brains were cut into sections for hematoxylin and eosin and immunohistochemical staining for poly(ADP-ribosyl)ation. Results - In the control group, there were no differences in the BA lumen caliber between baseline and day 2 (96.8 ± 10.4%). Cerebral vasospasm in the SAH+3-AB group (88.2±6.2%) was remarkably attenuated in comparison with that in the SAH-only group (64.9±8.0%) and the SAH + vehicle group (65.6±10.8%). The BA in the SAH + 3-AB group showed less corrugation of the tunica elastica interna than that in the SAH-only and SAH+vehicle groups. Staining for poly(ADP-ribosyl)ation was markedly inhibited in smooth muscle and adventitial cells of the BA in the SAH+3-AB group compared with other groups. Conclusions - Inhibiting ADP-ribosylation attenuates cerebral vasospasm after SAH in rabbits, and PARP activation may play an important role in the development of cerebral vasospasm.

Original languageEnglish
Pages (from-to)225-231
Number of pages7
JournalStroke
Volume32
Issue number1
Publication statusPublished - 2001

Fingerprint

Intracranial Vasospasm
Poly(ADP-ribose) Polymerases
Subarachnoid Hemorrhage
Rabbits
Basilar Artery
Adenosine Diphosphate
Injections
Angiography
Staining and Labeling
Cisterna Magna
Adventitia
Control Groups
Rubber
Hematoxylin
Eosine Yellowish-(YS)

Keywords

  • Nitric oxide synthase
  • Rabbits
  • Subarachnoid hemorrhage
  • Vasospasm

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Satoh, M., Date, I., Nakajima, M., Takahashi, K., Iseda, K., Tamiya, T., ... Asari, S. (2001). Inhibition of poly(ADP-ribose) polymerase attenuates cerebral vasospasm after subarachnoid hemorrhage in rabbits. Stroke, 32(1), 225-231.

Inhibition of poly(ADP-ribose) polymerase attenuates cerebral vasospasm after subarachnoid hemorrhage in rabbits. / Satoh, Motoyoshi; Date, Isao; Nakajima, Masaaki; Takahashi, Kenji; Iseda, Keiichi; Tamiya, Takashi; Ohmoto, Takashi; Ninomiya, Yoshifumi; Asari, Shoji.

In: Stroke, Vol. 32, No. 1, 2001, p. 225-231.

Research output: Contribution to journalArticle

Satoh, M, Date, I, Nakajima, M, Takahashi, K, Iseda, K, Tamiya, T, Ohmoto, T, Ninomiya, Y & Asari, S 2001, 'Inhibition of poly(ADP-ribose) polymerase attenuates cerebral vasospasm after subarachnoid hemorrhage in rabbits', Stroke, vol. 32, no. 1, pp. 225-231.
Satoh, Motoyoshi ; Date, Isao ; Nakajima, Masaaki ; Takahashi, Kenji ; Iseda, Keiichi ; Tamiya, Takashi ; Ohmoto, Takashi ; Ninomiya, Yoshifumi ; Asari, Shoji. / Inhibition of poly(ADP-ribose) polymerase attenuates cerebral vasospasm after subarachnoid hemorrhage in rabbits. In: Stroke. 2001 ; Vol. 32, No. 1. pp. 225-231.
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abstract = "Background and Purpose - Poly(ADP-ribose) polymerase (PARP) is important in modulating inflammation, which has been implicated in cerebral vasospasm after subarachnoid hemorrhage (SAH). We investigated the role of PARP in vasospasm using 3-aminobenzamide (3-AB), a PARP inhibitor, in a rabbit model. Methods - Twenty-four New Zealand White rabbits were divided into 4 groups: (1) no treatment (control group, n=6); (2) blood injection without pretreatment (SAH-only group, n=6); (3) blood injection with pretreatment by vehicle (SAH+vehicle group, n=6); and (4) blood injection with pretreatment by 3-AB (SAH+3-AB group, n=6). We used the single-hemorrhage model of SAH, injecting autologous arterial blood into the cisterna magna. Angiography was performed before (baseline) and after (day 2) SAH, and the diameter of the basilar artery (BA) was measured. Animals were euthanatized after the second angiogram. After perfusion and fixation, the brains were cut into sections for hematoxylin and eosin and immunohistochemical staining for poly(ADP-ribosyl)ation. Results - In the control group, there were no differences in the BA lumen caliber between baseline and day 2 (96.8 ± 10.4{\%}). Cerebral vasospasm in the SAH+3-AB group (88.2±6.2{\%}) was remarkably attenuated in comparison with that in the SAH-only group (64.9±8.0{\%}) and the SAH + vehicle group (65.6±10.8{\%}). The BA in the SAH + 3-AB group showed less corrugation of the tunica elastica interna than that in the SAH-only and SAH+vehicle groups. Staining for poly(ADP-ribosyl)ation was markedly inhibited in smooth muscle and adventitial cells of the BA in the SAH+3-AB group compared with other groups. Conclusions - Inhibiting ADP-ribosylation attenuates cerebral vasospasm after SAH in rabbits, and PARP activation may play an important role in the development of cerebral vasospasm.",
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AU - Satoh, Motoyoshi

AU - Date, Isao

AU - Nakajima, Masaaki

AU - Takahashi, Kenji

AU - Iseda, Keiichi

AU - Tamiya, Takashi

AU - Ohmoto, Takashi

AU - Ninomiya, Yoshifumi

AU - Asari, Shoji

PY - 2001

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N2 - Background and Purpose - Poly(ADP-ribose) polymerase (PARP) is important in modulating inflammation, which has been implicated in cerebral vasospasm after subarachnoid hemorrhage (SAH). We investigated the role of PARP in vasospasm using 3-aminobenzamide (3-AB), a PARP inhibitor, in a rabbit model. Methods - Twenty-four New Zealand White rabbits were divided into 4 groups: (1) no treatment (control group, n=6); (2) blood injection without pretreatment (SAH-only group, n=6); (3) blood injection with pretreatment by vehicle (SAH+vehicle group, n=6); and (4) blood injection with pretreatment by 3-AB (SAH+3-AB group, n=6). We used the single-hemorrhage model of SAH, injecting autologous arterial blood into the cisterna magna. Angiography was performed before (baseline) and after (day 2) SAH, and the diameter of the basilar artery (BA) was measured. Animals were euthanatized after the second angiogram. After perfusion and fixation, the brains were cut into sections for hematoxylin and eosin and immunohistochemical staining for poly(ADP-ribosyl)ation. Results - In the control group, there were no differences in the BA lumen caliber between baseline and day 2 (96.8 ± 10.4%). Cerebral vasospasm in the SAH+3-AB group (88.2±6.2%) was remarkably attenuated in comparison with that in the SAH-only group (64.9±8.0%) and the SAH + vehicle group (65.6±10.8%). The BA in the SAH + 3-AB group showed less corrugation of the tunica elastica interna than that in the SAH-only and SAH+vehicle groups. Staining for poly(ADP-ribosyl)ation was markedly inhibited in smooth muscle and adventitial cells of the BA in the SAH+3-AB group compared with other groups. Conclusions - Inhibiting ADP-ribosylation attenuates cerebral vasospasm after SAH in rabbits, and PARP activation may play an important role in the development of cerebral vasospasm.

AB - Background and Purpose - Poly(ADP-ribose) polymerase (PARP) is important in modulating inflammation, which has been implicated in cerebral vasospasm after subarachnoid hemorrhage (SAH). We investigated the role of PARP in vasospasm using 3-aminobenzamide (3-AB), a PARP inhibitor, in a rabbit model. Methods - Twenty-four New Zealand White rabbits were divided into 4 groups: (1) no treatment (control group, n=6); (2) blood injection without pretreatment (SAH-only group, n=6); (3) blood injection with pretreatment by vehicle (SAH+vehicle group, n=6); and (4) blood injection with pretreatment by 3-AB (SAH+3-AB group, n=6). We used the single-hemorrhage model of SAH, injecting autologous arterial blood into the cisterna magna. Angiography was performed before (baseline) and after (day 2) SAH, and the diameter of the basilar artery (BA) was measured. Animals were euthanatized after the second angiogram. After perfusion and fixation, the brains were cut into sections for hematoxylin and eosin and immunohistochemical staining for poly(ADP-ribosyl)ation. Results - In the control group, there were no differences in the BA lumen caliber between baseline and day 2 (96.8 ± 10.4%). Cerebral vasospasm in the SAH+3-AB group (88.2±6.2%) was remarkably attenuated in comparison with that in the SAH-only group (64.9±8.0%) and the SAH + vehicle group (65.6±10.8%). The BA in the SAH + 3-AB group showed less corrugation of the tunica elastica interna than that in the SAH-only and SAH+vehicle groups. Staining for poly(ADP-ribosyl)ation was markedly inhibited in smooth muscle and adventitial cells of the BA in the SAH+3-AB group compared with other groups. Conclusions - Inhibiting ADP-ribosylation attenuates cerebral vasospasm after SAH in rabbits, and PARP activation may play an important role in the development of cerebral vasospasm.

KW - Nitric oxide synthase

KW - Rabbits

KW - Subarachnoid hemorrhage

KW - Vasospasm

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