The role of statins in neurosurgery

Neurosurgical Review

Volumn 33, Issue 3, 2010, Pages 259-270

  Tapia Pérez, Jorge Humberto ^a   Sanchez Aguilar, Martin ^b   Schneider, Thomas ^a  

^a OTTO VON GUERICKE UNIVERSITY   (Germany)

^b UNIVERSIDAD AUTÓNOMA DE SAN LUIS POTOSÍ   (Mexico)

Author keywords

Apoptosis; Immunomodulation; Intracerebral hemorrhage; Statins; Subarachnoidal hemorrhage; Traumatic brain injury

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ATORVASTATIN; BETA INTERFERON; CARBOPLATIN; CARMUSTINE; FLUINDOSTATIN; GEFITINIB; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; MEVINOLIN; PLACEBO; ROSUVASTATIN; SIMVASTATIN; THALIDOMIDE; VINCRISTINE;

APOPTOSIS; BRAIN ANGIOGRAPHY; BRAIN HEMORRHAGE; BRAIN STEM TUMOR; CELL DEATH; CLINICAL TRIAL; DOPPLER ECHOGRAPHY; DRUG ACTIVITY; DRUG DOSE REDUCTION; DRUG MEGADOSE; GLIOBLASTOMA; GLIOMA; HUMAN; INCIDENCE; LOW DRUG DOSE; MEDLINE; MEDULLOBLASTOMA; MENINGIOMA; MORTALITY; MULTIPLE CYCLE TREATMENT; NEUROPROTECTION; NEUROSURGERY; NONHUMAN; PRIORITY JOURNAL; REVIEW; SUBARACHNOID HEMORRHAGE; SYSTEMATIC REVIEW; TRAUMATIC BRAIN INJURY; VASOSPASM;

BRAIN INJURIES; BRAIN NEOPLASMS; CEREBRAL HEMORRHAGE; GLIOBLASTOMA; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; NEUROSURGERY; NEUROSURGICAL PROCEDURES; SUBARACHNOID HEMORRHAGE;

EID: 77956465545     PISSN: 03445607     EISSN: None     Source Type: Journal    
DOI: 10.1007/s10143-010-0259-4     Document Type: Review

References (113)

1. Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE, Sillesen H, Simunovic L, Szarek M, Welch KM, Zivin JA, The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators (2006) High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 355:549-559
2. Arai Y, Yasuma T, Shitoto K, Yamauchi Y, Suzuki G (2000) Immunohistopathological study of intervertebral herniation of lumbar spine. J Orthop Sci 5:229-231
3. Asahi M, Huang Z, Thomas S, Yoshimura S, Sumii T, Mori T, Qiu J, Amin-Hanjani S, Huang PL, Liao JK, Lo EH, Moskowitz MA (2005) Protective effects of statins involving both eNOS and tPA in focal cerebral ischemia. J Cereb Blood Flow Metab 25:722-729
4. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R, Cholesterol Treatment Trialists' (CTT) Collaborators (2005) Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90, 056 participants in 14 randomised trials of statins. Lancet 366:1267-1278
5. Blanco M, Nombela F, Castellanos M, Rodriguez-Yáñez M, García-Gil M, Leira R, Lizasoain I, Serena J, Vivancos J, Moro MA, Dávalos A, Castillo J (2007) Statin treatment withdrawal in ischemic stroke: a controlled randomized study. Neurology 69:904-910
6. Bösel J, Gandor F, Harms C, Synowitz M, Harms U, Djoufack PC, Megow D, Dirnagl U, Hörtnagl H, Fink KB, Endres M (2005) Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neurones. J Neurochem 92:1386-1398
7. Bouterfa HL, Sattelmeyer V, Czub S, Vordermark D, Roosen K, Tonn JC (2000) Inhibition of Ras farnesylation by lovastatin leads to downregulation of proliferation and migration in primary cultured human glioblastoma cells. Anticancer Res 20:2761-2771
8. Cemeus C, Zhao TT, Barrett GM, Lorimer IA, Dimitroulakos J (2008) Lovastatin enhances gefitinib activity in glioblastoma cells irrespective of EGFRvIII and PTEN status. J Neurooncol 90:9-17
9. Chan DY, Chen GG, Poon WS, Liu PC (2008) Lovastatin sensitized human glioblastoma cells to TRAIL-induced apoptosis. J Neurooncol 86:273-283
10. Chen SF, Hung TH, Chen CC, Lin KH, Huang YN, Tsai HC, Wang JY (2007) Lovastatin improves histological and functional outcomes and reduces inflammation after experimental traumatic brain injury. Life Sci 81:288-298
11. Cheng G, Wei L, Zhi-Dan S, Shi-Guang Z, Xiang-Zhen L (2009) Atorvastatin ameliorates cerebral vasospasm and early brain injury after subarachnoid hemorrhage and inhibits caspasedependent apoptosis pathway. BMC Neurosci 10:7
12. Chou SH, Smith EE, Badjatia N, Nogueira RG, Sims JR 2nd, Ogilvy CS, Rordorf GA, Ayata C (2008) A randomized, doubleblind, placebo-controlled pilot study of simvastatin in aneurysmal subarachnoid hemorrhage. Stroke 39:2891-2893
13. http://clinicaltrials.gov/ct2/show/NCT00718328. Accessed 06 Jan 2009.
14. Déry MA, Rousseau G, Benderdour M, Beaumont E (2009) Atorvastatin prevents early apoptosis after thoracic spinal cord contusion injury and promotes locomotion recovery. Neurosci Lett 453:73-76
15. Eichel R, Khoury ST, Ben-Hur T, Keidar M, Paniri R, Leker RR (2010) Prior use of statins and outcome in patients with intracerebral haemorrhage. Eur J Neurol 17:78-83
16. Endres M, Laufs U, Liao JK, Moskowitz MA (2004) Targeting eNOS for stroke protection. Trends Neurosci 27:283-289
17. Fandino J, Fathi AR, Graupner T, Jacob S, Landolt H (2007) Perspectives in the treatment of subarachnoid hemorrhageinduced cerebral vasospasm. Neurocirugía 18:16-27, Spanish
18. FitzMaurice E, Wendell L, Snider R, Schwab K, Chanderraj R, Kinnecom C, Nandigam K, Rost NS, Viswanathan A, Rosand J, Greenberg SM, Smith EE (2008) Effect of statins on intracerebral hemorrhage outcome and recurrence. Stroke 39:2151-2154
19. Fletcher B, Berra K, Ades P, Braun LT, Burke LE, Durstine JL, Fair JM, Fletcher GF, Goff D, Hayman LL, Hiatt WR, Miller NH, Krauss R, Kris-Etherton P, Stone N, Wilterdink J, Winston M, Council on Cardiovascular Nursing, Council on Arteriosclerosis, Thrombosis, and Vascular Biology, Council on Basic Cardiovascular Sciences, Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Epidemiology and Prevention, Council on Nutrition, Physical Activity, and Metabolism, Council on Stroke, Preventive Cardiovascular Nurses Association (2005) Managing abnormal blood lipids: a collaborative approach. Circulation 112:3184-3209
20. Gabryś D, Dörfler A, Yaromina A, Hessel F, Krause M, Oertel R, Baumann M (2008) Effects of lovastatin alone or combined with irradiation on tumor cells in vitro and in vivo. Strahlenther Onkol 84:48-53
21. Gliemroth J, Zulewski H, Arnold H, Terzis AJ (2003) Migration, proliferation, and invasion of human glioma cells following treatment with simvastatin. Neurosurg Rev 26:117-124
22. Goldstein LB, Amarenco P, Szarek M, Callahan A 3rd, Hennerici M, Sillesen H, Zivin JA, Welch KM, SPARCL Investigators (2008) Hemorrhagic stroke in the stroke prevention by aggressive reduction in cholesterol levels study. Neurology 70:2364-2370
23. Gomis M, Ois A, Rodríguez-Campello A, Cuadrado-Godia E, Jiménez-Conde J, Subirana I, Dávalos A, Roquer J (2009) Outcome of intracerebral haemorrhage patients pre-treated with statins. Eur J Neurol 17:443-448
24. Greenwood J, Steinman L, Zamvil SS (2006) Statin therapy and autoimmune disease: from protein prenylation to immunomodulation. Nat Rev Immunol 6:358-370
25. Habtemariam A, Grönblad M, Virri J, Seitsalo S, Karaharju E (1998) Comparative immunohistochemical study of inflammatory cells in acute-stage and chronic-stage disc herniations. Spine 23:2159-2165
26. Hindler K, Cleeland CS, Rivera E, Collard CD (2006) The role of statins in cancer therapy. Oncologist 11:306-315
27. Hong H, Zeng JS, Kreulen DL, Kaufman DI, Chen AF (2006) Atorvastatin protects against cerebral infarction via inhibiting NADPH oxidase-derived superoxide in ischemic stroke. Am J Physiol Heart Circ Physiol 291: H2210-H2215
28. Iso H, Jacobs DR Jr, Wentworth D, Neaton JD, Cohen JD (1989) Serum cholesterol levels and six-year mortality from stroke in 350, 977 men screened for the Multiple Risk Factor Intervention Trial. N Engl J Med 320:904-910
29. Jiang Z, Zheng X, Lytle RA, Higashikubo R, Rich KM (2004) Lovastatin-induced up-regulation of the BH3-only protein, Bim, and cell death in glioblastoma cells. J Neurochem 89:168-178
30. Johnson MD, Woodard A, Okediji EJ, Toms SA, Allen GS (2002) Lovastatin is a potent inhibitor of meningioma cell proliferation: evidence for inhibition of a mitogen associated protein kinase. J Neurooncol 56:133-142
31. Jones KD, Couldwell WT, Hinton DR, Su Y, He S, Anker L, Law RE (1994) Lovastatin induces growth inhibition and apoptosis in human malignant glioma cells. Biochem Biophys Res Commun 205:1681-1687
32. Jung KH, Chu K, Jeong SW, Han SY, Lee ST, Kim JY, Kim M, Roh JK (2004) HMG-CoA reductase inhibitor, atorvastatin, promotes sensorimotor recovery, suppressing acute inflammatory reaction after experimental intracerebral hemorrhage. Stroke 35:1744-1749
33. Karki K, Knight RA, Han Y, Yang D, Zhang J, Ledbetter KA, Chopp M, Seyfried DM (2009) Simvastatin and atorvastatin improve neurological outcome after experimental intracerebral hemorrhage. Stroke 40:3384-3389
34. Karppinen J, Korhonen T, Malmivaara A, Paimela L, Kyllönen E, Lindgren KA, Rantanen P, Tervonen O, Niinimäki J, Seitsalo S, Hurri H (2003) Tumor necrosis factor-alpha monoclonal antibody, infliximab, used to manage severe sciatica. Spine 28:750-754
35. Kawaguchi S, Yamashita T, Yokogushi K, Murakami T, Ohwada O, Sato N (2001) Immunophenotypic analysis of the inflammatory infiltrates in herniated intervertebral discs. Spine 26:1209-1214
36. Kearney D, Fitzgerald D (1999) The anti-thrombotic effects of statins. J Am Coll Cardiol 33:1305-1307
37. Kern M, Lam MM, Knuckey NW, Lind CR (2009) Statins may not protect against vasospasm in subarachnoid haemorrhage. J Clin Neurosci 16:527-530
38. Koike Y, Uzuki M, Kokubun S, Sawai T (2003) Angiogenesis and inflammatory cell infiltration in lumbar disc herniation. Spine 28:1928-1933
39. Kopterides P, Falagas ME (2009) Statins for sepsis: a critical and updated review. Clin Microbiol Infect 15:325-334
40. Korhonen T, Karppinen J, Paimela L (2006) The treatment of disc-herniation-induced sciatica with infliximab-one year follow up results of FIRST II, a randomized clinical trial. Spine 31:2759-2766
41. Koyuturk M, Ersoz M, Altiok N (2004) Simvastatin induces proliferation inhibition and apoptosis in C6 glioma cells via c-jun N-terminal kinase. Neurosci Lett 370:212-217
42. Kramer AH, Fletcher JJ (2009) Statins in the management of patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. Neurocrit Care 42 (12):285-296
43. Kramer AH, Gurka MJ, Nathan B, Dumont AS, Kassell NF, Bleck TP (2008) Statin use was not associated with less vasospasm or improved outcome after subarachnoid hemorrhage. Neurosurgery 62:422-430
44. Lamprecht J, Wojcik C, Jakobisiak M, Stoehr M, Schrorter D, Paweletz N (1999) Lovastatin induces mitotic abnormalities in various cell lines. Cell Biol Int 23:51-60
45. Larner J, Jane J, Laws E, Packer R, Myers C, Shaffrey M (1998) A phase I-II trial of lovastatin for anaplastic astrocytoma and glioblastoma multiforme. Am J Clin Oncol 21:579-583
46. Laufs U, Endres M, Stagliano N, Amin-Hanjani S, Chui DS, Yang SX, Simoncini T, Yamada M, Rabkin E, Allen PG, Huang PL, Böhm M, Schoen FJ, Moskowitz MA, Liao JK (2000) Neuroprotection mediated by changes in the endothelial actin cytoskeleton. J Clin Invest 106:15-24
47. Lee SH, Bae HJ, Yoon BW, Kim H, Kim DE, Roh JK (2002) Low concentration of serum total cholesterol is associated with multifocal signal loss lesions on gradient-echo magnetic resonance imaging: analysis of risk factors for multifocal signal loss lesions. Stroke 33:2845-2849
48. Leker RR, Khoury ST, Rafaeli G, Shwartz R, Eichel R, Tanne D, NASIS Investigators (2009) Prior use of statins improves outcome in patients with intracerebral hemorrhage. Prospective data from the National Acute Stroke Israeli Surveys (NASIS). Stroke 40:2581-2584
49. Li B, Mahmood A, Lu D, Wu H, Xiong Y, Qu C, Chopp M (2009) Simvastatin attenuates microglial cells and astrocyte activation and decreases interleukin-1beta level after traumatic brain injury. Neurosurgery 65:179-186
50. López-Aguilar E, Sepúlveda-Vildósola AC, Betanzos-Cabrera Y, Rocha-Moreno YG, Gascón-Lastiri G, Rivera-Márquez H, Wanzke-del-Angel V, Cerecedo-Díaz F, de la Cruz-Yañez H (2008) Phase II study of metronomic chemotherapy with thalidomide, carboplatin-vincristine-fluvastatin in the treatment of brain stem tumors in children. Arch Med Res 39:655-662
51. Lu D, Goussev A, Chen J, Pannu P, Li Y, Mahmood A, Chopp M (2004) Atorvastatin reduces neurological deficit and increases synaptogenesis, angiogenesis, and neuronal survival in rats subjected to traumatic brain injury. J Neurotrauma 21:21-32
52. Lu D, Mahmood A, Goussev A, Schaller T, Qu C, Zhnag ZG, Li Y, Lu M, Chopp M (2004) Atorvastatin reduction of intravascular thrombosis, increase in cerebral microvascular patency and integrity, and enhancement of spatial learning in rats subjected to traumatic brain injury. J Neurosurg 101:813-821
53. Lu D, Mahmood A, Qu C, Goussev A, Lu M, Chopp M (2004) Atorvastatin reduction of intracranial hematoma volume in rats subjected to controlled cortical impact. J Neurosurg 101:822-825
54. Lu D, Qu C, Goussev A, Jiang H, Lu C, Schallert T, Mahmood A, Chen J, Li Y, Chopp M (2007) Statins increase neurogenesis in the dentate gyrus, reduce delayed neuronal death in the hippocampal CA3 region, and improve spatial learning in rat after traumatic brain injury. J Neurotrauma 24:1132-1146
55. Lynch JR, Wang H, McGirt MJ, Floyd J, Friedman AH, Coon AL (2005) Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage results of a pilot randomized clinical trial. Stroke 36:2024-2026
56. Macaulay RJ, Wang W, Dimitroulakos J, Becker LE, Yeger H (1999) Lovastatin-induced apoptosis of human medulloblastoma cell lines in vitro. J Neurooncol 42:1-11
57. MacDonald JS, Gerson RJ, Kornbrust DJ, Kloss MW, Prahalada S, Berry PH, Alberts AW, Bokelman DL (1988) Preclinical evaluation of lovastatin. Am J Cardiol 62:16J-27J
58. Maksymowych WP (2008) Do bisphosphonates and statins have a role in spondyloarthritis management? Curr Rheumatol Rep 10:364-370
59. Mason RP, Walter MF, Day CA, Jacob RF (2005) Intermolecular differences of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors contribute to distinct pharmacologic and pleiotropic actions. Am J Cardiol 96 (suppl): 11F-23F
60. McGirt MJ, Blessing R, Alexander MJ, Nimjee SH, Woodworth GF, Friedman AH, Graffagnino C, Laskowitz DT, Lynch JR (2006) Risk of cerebral vasopasm after subarachnoid hemorrhage reduced by statin therapy: a multivariate analysis of an institutional experience. J Neurosurg 105:671-674
61. McGirt MJ, Garces Ambrossi GL, Huang J, Tamargo RJ (2009) Simvastatin for the prevention of symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage: a singleinstitution prospective cohort study. J Neurosurg 110:968-974
62. McGirt MJ, Lynch JR, Parra A, Sheng H, Pearlstein RD, Laskowitz DT, Pelligrino DA, Warner DS (2002) Simvastatin increases endothelial nitric oxide synthase and ameliorates cerebral vasospasm resulting from subarachnoid hemorrhage. Stroke 33:2950-2956
63. McGirt MJ, Pradilla G, Legnani FG, Thai QA, Recinos PF, Tamargo RJ, Clatterbuck RE (2006) Systemic administration of simvastatin after the onset of experimental subarachnoid hemorrhage attenuates cerebral vasospasm. Neurosurgery 58:945-951
64. Meroni PL, Ventura D (2004) Statins and autoimmune diseases. APLAR J Rheumatol 7:278-284
65. Moskowitz SI, Ahrens C, Provencio JJ, Chow M, Rasmussen PA (2009) Prehemorrhage statin use and the risk of vasospasm after aneurysmal subarachnoid hemorrhage. Surg Neurol 71 (3):311-317
66. Murakami M, Goto T, Saito Y, Goto S, Kochi M, Ushio Y (2001) The inhibitory effect of simvastatin on growth in malignant gliomas-with special reference to its local application with fibrin glue spray in vivo. Int J Oncol 19:525-531
67. Narisawa T, Fukaura Y, Terada K, Umezawa A, Tanida N, Yazawa K, Ishikawa C (1994) Prevention of 1,2-dimethylhydrazineinduced colon tumorigenesis by HMG-CoA reductase inhibitors, pravastatin and simvastatin, in ICR mice. Carcinogenesis 15:2045-2048
68. Naval NS, Abdelhak TA, Urrunaga N, Zeballos P, Mirski MA, Carhuapoma JR (2008) An association of prior statin use with decreased perihematomal edema. Neurocrit Care 8:13-18
69. Naval NS, Abdelhak TA, Zeballos P, Urrunaga N, Mirski MA, Carhuapoma JR (2008) Prior statin use reduces mortality in intracerebral hemorrhage. Neurocrit Care 8:6-12
70. Obara S, Nakata M, Takeshima H, Kuratsu J, Maruyama I, Kitajima I (2002) Inhibition of migration of human glioblastoma cells by cerivastatin in association with focal adhesion kinase (FAK). Cancer Lett 185:153-161
71. Pannu R, Barbosa E, Singh AK, Singh I (2005) Attenuation of acute inflammatory response by atorvastatin after spinal cord injury in rats. J Neurosci Res 79:340-350
72. Pannu R, Christie DK, Barbosa E, Singh I, Singh AK (2007) Post-trauma Lipitor treatment prevents endothelial dysfunction, facilitates neuroprotection, and promotes locomotor recovery following spinal cord injury. J Neurochem 101:182-200
73. Parra A, Kreiter KT, Williams S, Sciacca R, Mack WJ, Naidech AM (2005) Effect of prior statin use on functional outcome and delayed vasospasm after acute aneurysmal subarachnoid hemorrhage: a matched controlled cohort study. Neurosurgery 56:476-484
74. Paul F, Waiczies S, Wuerfel J, Bellmann-Strobl J, Dörr J, Waiczies H, Haertle M, Wernecke KD, Volk HD, Aktas O, Zipp F (2008) Oral high-dose atorvastatin treatment in relapsing-remitting multiple sclerosis. PLoS ONE 3: e1928
75. Prasanna P, Thibault A, Liu L, Samid D (1996) Lipid metabolism as a target for brain cancer therapy: synergistic activity of lovastatin and sodium phenylacetate against human glioma cells. J Neurochem 66:710-716
76. Risselada R, Straatman H, van Kooten F, Dippel DW, van der Lugt A, Niessen WJ, Firouzian A, Herings RM, Sturkenboom MC (2009) Withdrawal of statins and risk of subarachnoid hemorrhage. Stroke 40:2887-2892
77. Robison RL, Suter W, Cox RH (1994) Carcinogenicity and mutagenicity studies with fluvastatin, a new, entirely synthetic HMG-CoA reductase inhibitor. Fundam Appl Toxicol 23:9-20
78. Rothoerl R, Woertgen C, Holzschuh M, Brehme K, Rüschoff J, Brawanski A (1998) Macrophage tissue infiltration, clinical symptoms, and signs in patients with lumbar disc herniation. A clinicopathological study on 179 patients. Acta Neurochir (Wien) 140:1245-1248
79. Scheen AJ, Radermecker RP, Sadzot B (2008) Statin for the brain: update in 2008. Rev Méd Liège 63:287-292, French
80. Seyfried D, Han Y, Lu D, Chen J, Bydon A, Chopp M (2004) Improvement in neurological outcome after administration of atorvastatin following experimental intracerebral hemorrhage in rats. J Neurosurg 101:104-107
81. Sillberg VA, Wells GA, Perry JJ (2008) Do statins improve outcomes and reduce the incidence of vasospasm after aneurysmal subarachnoid hemorrhage: a meta-analysis. Stroke 39:2622-2626
82. Smith PF, Grossman SJ, Gerson RJ, Gordon LR, Deluca JG, Majka JA, Wang RW, Germershausen JI, MacDonald JS (1991) Studies on the mechanism of simvastatin-induced thyroid hypertrophy and follicular cell adenoma in the rat. Toxicol Pathol 19:197-205
83. Soma MR, Baetta R, Bergamaschi S, De Renzis MR, Davegna C, Battaini F, Fumagalli R, Govoni S (1994) PKC activity in rat C6 glioma cells: changes associated with cell cycle and simvastatin treatment. Biochem Biophys Res Commun 200:1143-1149
84. Soma MR, Baetta R, De Renzis MR, Mazzini G, Davegna C, Magrassi L, Butti G, Pezzotta S, Paoletti R, Fumagalli R (1995) In vivo enhanced antitumor activity of carmustine [N, N′-bis (2-chloroethyl)-N-nitrosourea] by simvastatin. Cancer Res 55:597-602
85. Soma MR, Pagliarini P, Butti G, Paoletti R, Paoletti P, Fumagalli R (1992) Simvastatin, an inhibitor of cholesterol biosynthesis, shows a synergistic effect with N, N′-bis (2-chloroethyl)-N-nitrosourea and beta-interferon on human glioma cells. Cancer Res 52:4348-4355
86. http://www.stashtrial.com/home.html. Accessed 12 Sep. 2009
87. Sugawara T, Ayer R, Jadhav V, Chen W, Tsubokawa T, Zhang JH (2008) Simvastatin attenuation of cerebral vasospasm after subarachnoid hemorrhage in rats via increased phosphorylation of Akt and endothelial nitric oxide synthase. J Neurosci Res 86:3635-3643
88. Szapary L, Horvath B, Marton Z, Alexy T, Kesmarky G, Habon T, Szots M, Koltai K, Juricskay I, Czopf J, Toth K (2004) Shortterm effect of low-dose atorvastatin on haemorrheological parameters, platelet aggregation and endothelial function in patients with cerebrovascular disease and hyperlipidaemia. CNS Drugs 18:165-172
89. Tapia-Pérez H (2008) Intervertebral disc pathologies from an immunological perspective. Rev Neurol 46:751-757, Spanish
90. Tapia-Pérez JH, Sánchez-Aguilar M, Torres-Corzo JG, González-Aguirre D, Gordillo-Moscoso A, Rodríguez-Leyva I, Chalita-Williams JC (2009) Use of statins for the treatment of spontaneous intracerebral hemorrhage: results of a pilot study. Cen Eur Neurosurg 70:15-20
91. Tapia-Pérez JH, Sanchez-Aguilar M, Torres-Corzo JG, Gordillo-Moscoso A, Martinez-Perez P, Madeville P, de la Cruz-Mendoza E, Chalita-Williams J (2008) Effect of rosuvastatin on amnesia and disorientation after traumatic brain injury (NCT003229758). J Neurotrauma 25:1011-1017
92. Tapia-Pérez H, Sanchez-Aguilar M, Torres-Corzo J, Rodriguez-Leyva I, Herrera-Gonzalez LB (2007) Statins and brain protection mechanisms. Rev Neurol 45:359-364, Spanish
93. Tatsuta M, Iishi H, Baba M, Iseki K, Yano H, Uehara H, Yamamoto R, Nakaizumi A (1998) Suppression by pravastatin, an inhibitor of p21ras isoprenylation, of hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats. Br J Cancer 77:581-587
94. Terblanche M, Almog Y, Rosenson RS, Smith TS, Hackam DG (2006) Statins: panacea for sepsis? Lancet Infect Dis 6:242-248
95. Terblanche M, Almog Y, Rosenson RS, Smith TS, Hackam DG (2007) Statins and sepsis: multiple modifications at multiple levels. Lancet Infect Dis 7:358-368
96. Tseng MY, Czosnyka M, Richards H, Pickard JD, Kirkpatrick PJ (2005) Effects of acute treatment with pravastatin on cerebral vasospasm, autoregulation, and delayed ischemic deficits after aneurysmal subarachnoid hemorrhage: a phase II randomized placebo-controlled trial. Stroke 36:1627-1632
97. Tseng MY, Hutchinson PJ, Czosnyka M, Richards H, Pickard JD, Kirkpatrick PJ (2007) Effects of acute pravastatin treatment on intensity of rescue therapy, length of inpatient stay, and 6-month outcome in patients after aneurysmal subarachnoid hemorrhage. Stroke 38:1545-1550
98. Tseng MY, Hutchinson PJ, Turner CL, Czosnyka M, Richards H, Pickard JD, Kirkpatrick PJ (2007) Biological effects of acute pravastatin treatment in patients after aneurysmal subarachnoid hemorrhage: a double-blind, placebo-controlled trial. J Neurosurg 107:1092-1100 (Pubitemid 350255169)
99. Ulrich JA, Liebenberg EC, Thuillier DU, Lotz JC (2007) ISSLS prize winner: repeated disc injury causes persistent inflammation. Spine 32:2812-2819
100. van Denderen JC, Peters MJ, van Halm VP, van der Horst-Bruinsma IE, Dijkmans BA, Nurmohamed MT (2006) Statin therapy might be beneficial for patients with ankylosing spondylitis. Ann Rheum Dis 65:695-696
101. Vergouwen MD, Meijers JC, Geskus RB, Coert BA, Horn J, Stroes ES, van der Poll T, Vermeulen M, Roos YB (2009) Biologic effects of simvastatin in patients with aneurysmal subarachnoid hemorrhage: a double-blind, placebo-controlled randomized trial. J Cereb Blood Flow Metab 29:1444-1453
102. Virri J, Grönblad M, Seitsalo S, Habtemariam A, Kääpä E, Karaharju E (2001) Comparison of the prevalence of inflammatory cells in subtypes of disc herniations and associations with straight leg raising. Spine 26:2311-2315
103. Wang H, Lynch JR, Song P, Yang HJ, Yates RB, Mace B, Warner DS, Guyton JR, Laskowitz DT (2007) Simvastatin and atorvastatin improve behavioral outcome, reduce hippocampal degeneration, and improve cerebral blood flow after experimental traumatic brain injury. Exp Neurol 206:59-69
104. Wang W, Macaulay RJ (1999) Mevalonate prevents lovastatininduced apoptosis in medulloblastoma cell lines. Can J Neurol Sci 26:305-310
105. Wang W, Macaulay RJ (2003) Cell-cycle gene expression in lovastatin-induced medulloblastoma apoptosis. Can J Neurol Sci 30:349-357
106. Waters DD (2005) Safety of high-dose atorvastatin therapy. Am J Cardiol 96(suppl):69F-75F
107. Weitz-Schmidt G, Welzenbach K, Dawson J, Kallen J (2004) Improved lymphocyte function-associated antigen-1 (LFA-1) inhibition by statin derivatives: molecular basis determined by x-ray analysis and monitoring of LFA-1 conformational changes in vitro and ex vivo. J Biol Chem 279:46764-46771
108. Wiviott SD, Cannon CP, Morrow DA, Ray KK, Pfeffer MA, Braunwald E, PROVE IT-TIMI 22 Investigators (2005) Can lowdensity lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy. J Am Coll Cardiol 46:1411-1416
109. Woo D, Kissela BM, Khoury JC, Sauerbeck LR, Haverbusch MA, Szaflarski JP, Gebel JM, Pancioli AM, Jauch EC, Schneider A, Kleindorfer D, Broderick JP (2004) Hypercholesterolemia, HMG-CoA reductase inhibitors, and risk of intracerebral hemorrhage: a case-control study. Stroke 35:1360-1364
110. Wu H, Lu D, Jiang H, Xiong Y, Qu C, Li B, Mahmood A, Zhou D, Chopp M (2008) Simvastatin-mediated upregulation of VEGF and BDNF, activation of the PI3K/Akt pathway, and increase of neurogenesis are associated with therapeutic improvement after traumatic brain injury. J Neurotrauma 25:130-139
111. Yano K, Reed DM, MacLean CJ (1989) Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program. Stroke 20:1460-1465
112. Yao CJ, Lai GM, Chan CF, Cheng AL, Yang YY, Chuang SE (2006) Dramatic synergistic anticancer effect of clinically achievable doses of lovastatin and troglitazone. Int J Cancer 118:773-779
113. Zhang X, Patel A, Horibe H, Wu Z, Barzi F, Rodgers A, MacMahon S, Woodward M, Asia Pacific Cohort Studies Collaboration (2003) Cholesterol, coronary heart disease, and stroke in the Asia Pacific region. Int J Epidemiol 32:563-572