Inhibition of poly(ADP-ribose) polymerase attenuates cerebral vasospasm after subarachnoid hemorrhage in rabbits.
OBJECTIVE
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.
Satoh
M
M
Department of Neurological Surgery, Okayama University Medical School (Japan).
Date
I
I
Nakajima
M
M
Takahashi
K
K
Iseda
K
K
Tamiya
T
T
Ohmoto
T
T
Ninomiya
Y
Y
Asari
S
S
D000818:Animals; D001488:Basilar Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D001549:Benzamides / Q000008:administration & dosage; D002533:Cerebral Angiography; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D007150:Immunohistochemistry; D007267:Injections; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D020301:Vasospasm, Intracranial / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology
D001549:Benzamides; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases