caa a22 4500 606213937 CHVBK 20210128101049.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s00701-015-2399-3 doi (NATIONALLICENCE)springer-10.1007/s00701-015-2399-3 Preconditioning with pitavastatin, an HMG-CoA reductase inhibitor, attenuates C-Jun N-terminal kinase activation in experimental subarachnoid hemorrhage-induced apoptosis [Elektronische Daten] [Chih-Zen Chang, Shu-Chuan Wu, Aij-Lie Kwan, Chih-Lung Lin] Background: Accumulating results have disclosed that early brain injury (EBI) may play a major role in the determination of the outcome of aneurysmal subarachnoid hemorrhage (SAH) patients. This study is of interest to examine the efficacy of pitavastatin, a 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase) inhibitor, on SAH-induced apoptosis. Methods: A rodent double SAH model was employed. Pitavastatin was administered orally. CSF IL-1β, IL-6, IL-8 and TNF-α were measured (rt-PCR). Basilar arteries were harvested for C-Jun N-terminal kinase p46/p55 (cJNK (p46/p55)), matrix metallopeptidase-9 (MMP-9) (Western blot), caspase and Bcl-2 (rt-PCR) evaluation. Results: Pitavastatin reduced the bioexpression of cJNK p55 compared with the SAH groups. Cleaved caspase-9a was significantly reduced in the pitavastatin-preconditioned group compared with the SAH group (p > 0.05). IL-1β and TNF-α levels were reduced in the pitavastatin-preconditioned group. Pretreatment with pitavastatin significantly reduced activated MMP-9, capsase-9a and B-cell lymphoma 2(Bcl) mRNA. Conclusion: Preconditioning with pitavastatin exerts its neuroprotective effect through the dual action of inhibiting cJNK(p46/p55) activation and reducing cleaved caspase-9a expression. Besides, the bioinhibition of MMP-9 may partially contribute to the neuroprotective effect. This study lends credence to the theory that statins, especially in the preconditioning status, may attenuate SAH-induced neuron apoptosis. Springer-Verlag Wien, 2015 Pitavastatin nationallicence Early brain injury nationallicence cJNK p46/p55 nationallicence HMG-CoA reductase nationallicence Matrix metallopeptidase-9 nationallicence Subarachnoid hemorrhage nationallicence BA : Basilar artery nationallicence Caspases : Cysteine-requiring aspartate proteases nationallicence Bcl : B-cell lymphoma 2 nationallicence CSF : Cerebrospinal fluid nationallicence EBI : Early brain injury nationallicence ET : Endothelin nationallicence HMG-CoA reductase : 3-Hydroxy-3-methyl-glutaryl-CoA reductase nationallicence HRP : Horseradish peroxidase nationallicence IEL : Internal elastic lamina nationallicence IL-1 and -6 : Interleukin 1 and 6 nationallicence cJNK1/2 : C-Jun N-terminal kinase 1/2 nationallicence MMP-9 : Matrix metallopeptidase-9 nationallicence PBS : Phosphate-buffered saline nationallicence PGE2 : Prostaglandin E2 nationallicence SAH : Subarachnoid hemorrhage nationallicence MCP-1 : Monocyte chemotactic protein 1 nationallicence Chang Chih-Zen Department of Surgery, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan aut Wu Shu-Chuan Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung, Taiwan, Republic of China aut Kwan Aij-Lie Department of Surgery, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan aut Lin Chih-Lung Department of Surgery, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan aut Acta Neurochirurgica Springer Vienna 157/6(2015-06-01), 1031-1041 0001-6268 157:6<1031 2015 157 701 https://doi.org/10.1007/s00701-015-2399-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00701-015-2399-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chang Chih-Zen Department of Surgery, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan aut NATIONALLICENCE 700 1- Wu Shu-Chuan Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung, Taiwan, Republic of China aut NATIONALLICENCE 700 1- Kwan Aij-Lie Department of Surgery, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan aut NATIONALLICENCE 700 1- Lin Chih-Lung Department of Surgery, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan aut NATIONALLICENCE 773 0- Acta Neurochirurgica Springer Vienna 157/6(2015-06-01), 1031-1041 0001-6268 157:6<1031 2015 157 701