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

Abstract

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.

Gene expression profiles and related immune-inflammatory factors in the cerebral arteries in mouse models of subarachnoid haemorrhage

“…Rasmussen et al [12] found that the occurrence of CVS in SAH animal models was associated with the increase of tumour necrosis factor-a (TNF-a) level. Inhibition of the TNF-a level rescued the brain injury and alleviated the occurrence of cerebrovascular events [13]. Therefore, TNF-a may be a new intervention target for the prevention and treatment of CVS [14].…”

Characterization and ACE Inhibitory Activity of Fermented Milk with Probiotic Lactobacillus plantarum K25 as Analyzed by GC-MS-Based Metabolomics Approach

“…Alanine could prevent kidney stones, assist glucose metabolism, help ease hypoglycemia, and improve physical energy [ 52 ]. Furthermore, an increased level of ribose in the probiotic L. plantarum K25 fermented milk might be beneficial since oral administration of ribose was reported to improve athletic performance by boosting muscle energy and making it readily available, and also to improve symptoms of diseases such as chronic fatigue syndrome, fibromyalgia and coronary artery disease [ 53 ]. Finally, 1,3-dihydroxyacetone was a three-carbon compound in glycolysis that promoted athletic performance [ 54 ].…”

Dysregulation of Serum MicroRNA after Intracerebral Hemorrhage in Aged Mice

“…Our findings show the increased level of miR-137-3p in the serum of aged mice after ICH in comparison to sham. Upregulation of miR-137-3p inhibited neuronal death, parthanatos, a type of programmed cell necrosis associated with ICH [ 52 , 146 , 147 , 148 , 149 ]. In addition, upregulation of miR-137-3p resulted in neuroprotective effects by decreasing neuronal nitric oxide synthase-positive cells and the death of motor neurons after avulsion injury to the spinal cord in rats [ 53 ].…”