Potential role of poly (ADP-ribose) polymerase in delayed cerebral vasospasm following subarachnoid hemorrhage in rats.

Poly (ADP-ribose) polymerase (PARP) serves a key role in several neurological disorders, however, the specific role of PARP in delayed cerebral vasospasm (DCVS) following subarachnoid hemorrhage (SAH) remains unclear. The present study was conducted to clarify the possible mechanism of PARP in DCVS with the treatment of 3-aminobenzamide (3-AB), a PARP inhibitor. In the preliminary experiment, an internal carotid artery puncture SAH model, a cisterna magna double injection SAH model and prechiasmatic cistern single injection SAH model were compared with respect to mortality and neurobehavioral test results. The prechiasmatic cistern single injection SAH model was chosen to induce DCVS in the formal experiment. In the formal experiment, a total of 96 Sprague Dawley rats were randomly allocated into the sham group, the SAH group and the SAH+3-AB group and then each group was further subdivided into days 3, 5, 7 and 14 post-SAH subgroups (n=8 for each subgroup). The prechiasmatic cistern single injection SAH model was established to induce DCVS. Neurobehavioral testing and HE staining were conducted to evaluate the degree of cerebral vasospasm. PARP activity was assessed by ELISA and immunohistochemistry. An electrophoretic mobility shift assay was used to detect nuclear factor (NF)-κB DNA-binding activity. The expression of monocyte chemotactic protein 1 (MCP-1) and C-reactive protein (CRP) were measured by western blotting. Cerebral vasospasm occurred following SAH and became most severe on around day 7 post-SAH. NF-κB activity, PARP activity, the expression of MCP-1 and CRP exhibited a similar time course to cerebral vasospasm. Treatment with 3-AB alleviated the degree of cerebral vasospasm. NF-κB activity, PARP activity and the expression of MCP-1 and CRP were also suppressed by 3-AB treatment. In conclusion, PARP may serve an important role in regulating the inflammatory response and ultimately contribute to DCVS. Therefore 3-AB may be a potential therapeutic agent for DCVS.