Effects of simvastatin and taurine on delayed cerebral vasospasm following subarachnoid hemorrhage in rabbits

Lin,Cheng; Zhao,Yuanli; Wan,Gang; Zhu,Anlin; Wang,Hao

doi:10.3892/etm.2016.3082

Effects of simvastatin and taurine on delayed cerebral vasospasm following subarachnoid hemorrhage in rabbits

Authors:
- Cheng Lin
- Yuanli Zhao
- Gang Wan
- Anlin Zhu
- Hao Wang
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Affiliations: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China, Department of Neurosurgery, Civil Aviation General Hospital, Beijing 100123, P.R. China
Published online on: February 16, 2016 https://doi.org/10.3892/etm.2016.3082
Pages: 1355-1360

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Abstract

The aim of the current study was to observe the effects of simvastatin and taurine on delayed cerebral vasospasm (DCVS) following experimental subarachnoid hemorrhage (SAH) in rabbits. A total of 48 New Zealand white rabbits were allocated at random into four groups (control, SAH, SAH + simvastatin and SAH + taurine groups; n=12 each). The rabbit model of DCVS was established using a double hemorrhage method, which involved injecting autologous arterial blood into the cisterna magna in the SAH groups. The SAH + simvastatin group was administered oral simvastatin (5 mg/kg) daily between days 0‑6. The SAH + taurine group was administered oral taurine (50 mg/kg) daily between days 0‑6. Starch (50 mg/kg) was administered orally to the animals in the other two groups (control and SAH groups). The control group were not subjected to any other injections or treatment. The internal diameter and internal diameter/wall thickness of the basilar artery (BA) were measured. The expression levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β and IL‑6 were determined using immunohistochemical and quantitative polymerase chain reaction methods following the sacrifice of all animals on day 7. The activity of nuclear factor (NF)‑κB in the BA was also measured using an electrophoretic mobility shift assay. The BA walls in the SAH + simvastatin and SAH + taurine groups exhibited reduced narrowing and corrugation of the tunica elastica interna compared with the SAH group. At the protein and cDNA levels, it was found that cerebral vasospasm of the BA in the SAH + simvastatin and SAH + taurine groups was alleviated, as indicated by the reduced expression of TNF‑α, IL‑1β, IL‑6 and NF‑κB compared with the SAH group (P<0.05). In conclusion, simvastatin and taurine reduced DCVS following SAH in rabbits, which suggests that these compounds may exert anti-inflammatory effects.

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1	Kerz T, Victor A, Beyer C, Trapp I, Heid F and Reisch R: A case control study of statin and magnesium administration in patients after aneurysmal subarachnoid hemorrhage: Incidence of delayed cerebral ischemia and mortality. Neurol Res. 30:893–897. 2008. View Article : Google Scholar : PubMed/NCBI
2	Suzuki H, Kanamaru K, Shiba M, Fujimoto M, Kawakita F, Imanaka-Yoshida K, Yoshida T and Taki W: Tenascin-C is a possible mediator between initial brain injury and vasospasm-related and -unrelated delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Acta Neurochir Suppl. 120:117–121. 2015.PubMed/NCBI
3	da Costa L, Fisher J, Mikulis DJ, Tymianski M and Fierstra J: Early identification of brain tissue at risk for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Acta Neurochir Suppl. 120:105–109. 2015.PubMed/NCBI
4	Hirashima Y, Endo S, Kato R and Takaku A: Prevention of cerebrovasospasm following subarachnoid hemorrhage in rabbits by the platelet-activating factor antagonist, E5880. J Neurosurg. 84:826–830. 1996. View Article : Google Scholar : PubMed/NCBI
5	Dumont AS, Dumont RJ, Chow MM, Lin CL, Calisaneller T, Ley KF, Kassell NF and Lee KS: Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation. Neurosurgery. 53:123–133; discussion 133–125. 2003. View Article : Google Scholar : PubMed/NCBI
6	Lin CL, Dumont AS, Calisaneller T, Kwan AL, Hwong SL and Lee KS: Monoclonal antibody against E selectin attenuates subarachnoid hemorrhage-induced cerebral vasospasm. Surg Neurol. 64:201–205; discussion 205–206. 2005. View Article : Google Scholar : PubMed/NCBI
7	Kim E, Kim HC, Park SY, Lim YJ, Ro SH, Cho WS, Jeon YT, Hwang JW and Park HP: Effect of red blood cell transfusion on unfavorable neurological outcome and symptomatic vasospasm in patients with cerebral aneurysmal rupture: Old versus fresh blood. World Neurosurg. Aug 28–2015.(Epub ahead of print).
8	Nickele C, Muro K, Getch CC, Walker MT and Bernstein RA: Severe reversible cerebral vasoconstriction syndrome mimicking aneurysmal rupture and vasospasm. Neurocrit Care. 7:81–85. 2007. View Article : Google Scholar : PubMed/NCBI
9	Salunke P, Patra DP and Mukherjee KK: Delayed cerebral vasospasm and systemic inflammatory response syndrome following intraoperative rupture of cerebral hydatid cyst. Acta Neurochir (Wien). 156:613–614. 2014. View Article : Google Scholar : PubMed/NCBI
10	Li W, Zheng T, Altura BT and Altura BM: Antioxidants prevent elevation in [Ca(2+)](i) induced by low extracellular magnesium in cultured canine cerebral vascular smooth muscle cells: Possible relationship to Mg(2+) deficiency-induced vasospasm and stroke. Brain Res Bull. 52:151–154. 2000. View Article : Google Scholar : PubMed/NCBI
11	Heffren J, McIntosh AM and Reiter PD: Nimodipine for the prevention of cerebral vasospasm after subarachnoid hemorrhage in 12 children. Pediatr Neurol. 52:356–360. 2015. View Article : Google Scholar : PubMed/NCBI
12	Munakata A, Ohkuma H and Shimamura N: Effect of a free radical scavenger, edaravone, on free radical reactions: Related signal transduction and cerebral vasospasm in the rabbit subarachnoid hemorrhage model. Acta Neurochir Suppl. 110:17–22. 2011.PubMed/NCBI
13	Nishziawa S: Roles of signal transduction mechanisms in cerebral vasospasm following subarachnoid hemorrhage: Overview. Acta Neurochir Suppl. 110:27–30. 2011.PubMed/NCBI
14	Zubkov AY, Nanda A and Zhang JH: Signal transduction pathways in cerebral vasospasm. Pathophysiology. 9:47–61. 2003. View Article : Google Scholar : PubMed/NCBI
15	Jośko J, Hendryk S, Jedrzejowska-Szypułka H, Słowiński J, Gwóźdź B, Lange D, Snietura M, Zwirska-Korczala K and Jochem J: Cerebral angiogenesis after subarachnoid hemorrhage (SAH) and endothelin receptor blockage with BQ-123 antagonist in rats. J Physiol Pharmacol. 52:237–248. 2001.PubMed/NCBI
16	Zhou ML, Zhu L, Wang J, Hang CH and Shi JX: The inflammation in the gut after experimental subarachnoid hemorrhage. J Surg Res. 137:103–108. 2007. View Article : Google Scholar : PubMed/NCBI
17	Sarrafzadeh A, Copin JC, Bengualid DJ, Turck N, Vajkoczy P, Bijlenga P, Schaller K and Gasche Y: Matrix metalloproteinase-9 concentration in the cerebral extracellular fluid of patients during the acute phase of aneurysmal subarachnoid hemorrhage. Neurol Res. 34:455–461. 2012. View Article : Google Scholar : PubMed/NCBI
18	De Martin R, Hoeth M, Hofer-Warbinek R and Schmid JA: The transcription factor NF-kappa B and the regulation of vascular cell function. Arterioscler Thromb Vasc Biol. 20:E83–E88. 2000. View Article : Google Scholar : PubMed/NCBI
19	Song YS, Lee YS and Chan PH: Oxidative stress transiently decreases the IKK complex (IKKalpha, beta, and gamma), an upstream component of NF-kappaB signaling, after transient focal cerebral ischemia in mice. J Cereb Blood Flow Metab. 25:1301–1311. 2005. View Article : Google Scholar : PubMed/NCBI
20	Huang CY, Fujimura M, Noshita N, Chang YY and Chan PH: SOD1 down-regulates NF-kappaB and c-Myc expression in mice after transient focal cerebral ischemia. J Cereb Blood Flow Metab. 21:163–173. 2001. View Article : Google Scholar : PubMed/NCBI
21	Wu W, Guan Y, Zhao G, Fu XJ, Guo TZ, Liu YT, Ren XL, Wang W, Liu HR and Li YQ: Elevated IL-6 and TNF-α levels in cerebrospinal fluid of subarachnoid hemorrhage patients. Mol Neurobiol. Jun 11–2015.(Epub ahead of print). View Article : Google Scholar
22	Young AM, Karri SK, You W and Ogilvy CS: Specific TNF-alpha inhibition in cerebral aneurysm formation and subarachnoid hemorrhage. Curr Drug Saf. 7:190–196. 2012. View Article : Google Scholar : PubMed/NCBI
23	Hanafy KA, Grobelny B, Fernandez L, Kurtz P, Connolly ES, Mayer SA, Schindler C and Badjatia N: Brain interstitial fluid TNF-alpha after subarachnoid hemorrhage. J Neurol Sci. 291:69–73. 2010. View Article : Google Scholar : PubMed/NCBI
24	Pinchuk TV, Fedulaev YN, Khairetdinova GA, Denisova NN, Chura OV and Logunova IY: Anti-inflammatory effects of simvastatin in patients with chronic heart failure. Bull Exp Biol Med. 157:552–554. 2014. View Article : Google Scholar : PubMed/NCBI
25	Sun M, Zhao Y, Gu Y and Xu C: Anti-inflammatory mechanism of taurine against ischemic stroke is related to down-regulation of PARP and NF-κB. Amino Acids. 42:1735–1747. 2012. View Article : Google Scholar : PubMed/NCBI
26	Seiyama A, Yoshikawa N and Imamura Y: Ischemic pretreatment delays ischemic brain vasospasm injury in gerbils. Adv Exp Med Biol. 812:247–252. 2014. View Article : Google Scholar : PubMed/NCBI
27	Zhang H, Zhang B and Li S, Liang C, Xu K and Li S: Whole brain CT perfusion combined with CT angiography in patients with subarachnoid hemorrhage and cerebral vasospasm. Clin Neurol Neurosurg. 115:2496–2501. 2013. View Article : Google Scholar : PubMed/NCBI
28	Suarez JI, Tarr RW and Selman WR: Aneurysmal subarachnoid hemorrhage. N Engl J Med. 354:387–396. 2006. View Article : Google Scholar : PubMed/NCBI
29	Miyazaki T and Matsuzaki Y: Taurine and liver diseases: A focus on the heterogeneous protective properties of taurine. Amino Acids. 46:101–110. 2014. View Article : Google Scholar : PubMed/NCBI
30	Juvela S: Nonsteroidal anti-inflammatory drugs as risk factors for spontaneous intracerebral hemorrhage and aneurysmal subarachnoid hemorrhage. Stroke. 34:e34–e36. 2003. View Article : Google Scholar : PubMed/NCBI
31	Joo K, Lee Y, Choi D, Han J, Hong S, Kim YM and Jung Y: An anti-inflammatory mechanism of taurine conjugated 5-aminosalicylic acid against experimental colitis: Taurine chloramine potentiates inhibitory effect of 5-aminosalicylic acid on IL-1beta-mediated NFkappaB activation. Eur J Pharmacol. 618:91–97. 2009. View Article : Google Scholar : PubMed/NCBI
32	Marcinkiewicz J, Kurnyta M, Biedroń R, Bobek M, Kontny E and Maśliński W: Anti-inflammatory effects of taurine derivatives (taurine chloramine, taurine bromamine, and taurolidine) are mediated by different mechanisms. Adv Exp Med Biol. 583:481–492. 2006. View Article : Google Scholar : PubMed/NCBI
33	Quinn MR, Barua M, Liu Y and Serban V: Taurine chloramine inhibits production of inflammatory mediators and iNOS gene expression in alveolar macrophages; a tale of two pathways: Part I, NF-kappaB signaling. Adv Exp Med Biol. 526:341–348. 2003. View Article : Google Scholar : PubMed/NCBI
34	Buechler C, Ullrich H, Aslanidis C, Bared SM, Lingenhel A, Ritter M and Schmitz G: Lipoprotein (a) downregulates lysosomal acid lipase and induces interleukin-6 in human blood monocytes. Biochim Biophys Acta. 1642:25–31. 2003. View Article : Google Scholar : PubMed/NCBI
35	Coppack SW: Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc. 60:349–356. 2001. View Article : Google Scholar : PubMed/NCBI
36	Hotamisligil GS, Arner P, Caro JF, Atkinson RL and Spiegelman BM: Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest. 95:2409–2415. 1995. View Article : Google Scholar : PubMed/NCBI
37	Asahi M, Huang Z, Thomas S, Yoshimura S, Sumii T, Mori T, Qiu J, Amin-Hanjani S, Huang PL, Liao JK, et al: Protective effects of statins involving both eNOS and tPA in focal cerebral ischemia. J Cereb Blood Flow Metab. 25:722–729. 2005. View Article : Google Scholar : PubMed/NCBI
38	Kramer AH: Statins in the management of aneurysmal subarachnoid hemorrhage: An overview of animal research, observational studies, randomized controlled trials and meta-analyses. Acta Neurochir Suppl. 110:193–201. 2011.PubMed/NCBI
39	Sabri M and Macdonald RL: Statins: A potential therapeutic addition to treatment for aneurysmal subarachnoid hemorrhage? World Neurosurg. 73:646–653. 2010. View Article : Google Scholar : PubMed/NCBI
40	Rasmussen LM, Hansen PR, Nabipour MT, Olesen P, Kristiansen MT and Ledet T: Diverse effects of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase on the expression of VCAM-1 and E-selectin in endothelial cells. Biochem J. 360:363–370. 2001. View Article : Google Scholar : PubMed/NCBI
41	Zelvyte I, Dominaitiene R, Crisby M and Janciauskiene S: Modulation of inflammatory mediators and PPARgamma and NFkappaB expression by pravastatin in response to lipoproteins in human monocytes in vitro. Pharmacol Res. 45:147–154. 2002. View Article : Google Scholar : PubMed/NCBI
42	Kaji H, Kanatani M, Sugimoto T and Chihara K: Statins modulate the levels of osteoprotegerin/receptor activator of NFkappaB ligand mRNA in mouse bone-cell cultures. Horm Metab Res. 37:589–592. 2005. View Article : Google Scholar : PubMed/NCBI
43	Ahn KS, Sethi G and Aggarwal BB: Reversal of chemoresistance and enhancement of apoptosis by statins through down-regulation of the NF-kappaB pathway. Biochem Pharmacol. 75:907–913. 2008. View Article : Google Scholar : PubMed/NCBI