Prophylactic but not delayed administration of simvastatin protects against long-lasting cognitive and morphological consequences of neonatal hypoxic-ischemic brain injury, reduces interleukin-1β and tumor necrosis factor-α mRNA induction, and does not affect endothelial nitric oxide synthase expression

Stroke

Volumn 34, Issue 8, 2003, Pages 2007-2012

  Balduini, Walter ^a   Mazzoni, Erika ^a   Carloni, Silvia ^a   De Simoni, Maria Grazia ^b   Perego, Carlo ^b   Sironi, Luigi ^c   Cimino, Mauro ^a  

^a UNIVERSITY OF URBINO   (Italy)

^b MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

^c UNIVERSITY OF MILAN   (Italy)

Author keywords

Cerebral ischemia; HMG CoA reductase inhibitors; Neuroprotection; Newborn; Rats

Indexed keywords

INTERLEUKIN 1BETA; NITRIC OXIDE SYNTHASE; SIMVASTATIN; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BEHAVIOR; BRAIN HYPOXIA; BRAIN INJURY; BRAIN ISCHEMIA; COGNITIVE DEFECT; CONTROLLED STUDY; DRUG EFFECT; HISTOLOGY; INFLAMMATION; MAZE TEST; MORPHOLOGY; NEUROPROTECTION; NEWBORN; NONHUMAN; PRIORITY JOURNAL; PROPHYLAXIS; PROTEIN EXPRESSION; PROTEIN INDUCTION; RAT; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; STROKE; WESTERN BLOTTING;

ANIMALS; ANIMALS, NEWBORN; BODY WEIGHT; BRAIN; BRAIN CHEMISTRY; CHOLESTEROL; COGNITION DISORDERS; DISEASE MODELS, ANIMAL; DRUG ADMINISTRATION SCHEDULE; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPOXIA-ISCHEMIA, BRAIN; INTERLEUKIN-1; MALE; MAZE LEARNING; NEUROPROTECTIVE AGENTS; NITRIC OXIDE SYNTHASE; NITRIC OXIDE SYNTHASE TYPE III; RATS; RATS, SPRAGUE-DAWLEY; RNA, MESSENGER; SIMVASTATIN; TIME FACTORS; TREATMENT OUTCOME; TUMOR NECROSIS FACTOR-ALPHA;

EID: 0042122374     PISSN: 00392499     EISSN: None     Source Type: Journal    
DOI: 10.1161/01.STR.0000080677.24419.88     Document Type: Article

References (21)

1. Blauw GJ, Lagaay AM, Smelt AH, Westendorp RG. Stroke, statins, and cholesterol: a meta-analysis of randomized, placebo-controlled, double-blind trials with HMG-CoA reductase inhibitors. Stroke. 1997;28:946-950.
2. Weitz-Schmidt G. Statins as anti-inflammatory agents. Trends Pharmacol Sci. 2002;23:482.
3. Vaughan CJ, Delanty N. Neuroprotective properties of statins in cerebral ischemia and stroke. Stroke. 1999;30:1969-1973.
4. Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arterioscler Thromb Vasc Biol. 2001;21:1712-1719.
5. Endres M, Laufs U, Huang Z, Nakamura T, Huang P, Moskowitz MA, Liao JK. Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 1998;95:8880-8885.
6. Yamada M, Huang Z, Dalkara T, Endres M, Laufs U, Waeber C, Huang PL, Liao JK, Moskowitz MA. Endothelial nitric oxide synthase-dependent cerebral blood flow augmentation by L-arginine after chronic statin treatment. J Cereb Blood Flow Metab. 2000;20:709-717.
7. Pruefer D, Scalia R, Lefer AM, Simvastatin inhibits leukocyte-endothelial cell interactions and protects against inflammatory processes in normocholesterolemic rats. Arterioscler Thromb Vasc Biol. 1999;19:2894-2900.
8. Pahan K, Sheikh FG, Namboodiri AM, Singh I, Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages. J Clin Invest. 1997;100:2671-2679.
9. Kureishi Y, Luo Z, Shiojima I, Bialik A, Fulton D, Lefer DJ, Sessa WC, Walsh K. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase akt and promotes angiogenesis in normocholesterolemic animals. Nat Med. 2000;6:1004-1010.
10. Lynch JK, Nelson KB. Epidemiology of perinatal stroke. Curr Opin Pediatr. 2001;13:499-505.
11. Rice JED, Vannucci RC, Brierley JB. The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol. 1981;9:131-141.
12. Balduini W, De Angelis V, Mazzoni E, Cimino M. Simvastatin protects against long-lasting behavioral and morphological consequences of neonatal hypoxic/ischemic brain injury. Stroke. 2001;32:2185-2191.
13. Balduini W, De Angelis V, Mazzoni E, Cimino M. Long-lasting behavioral alterations following a hypoxic/ischemic brain injury in neonatal rats. Brain Res. 2000;859:318-325.
14. De Simoni MG, Perego C, Ravizza T, Moneta D, Conti M, Marchesi F, De Luigi A, Garattini S, Vezzani A. Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. Eur J Neurosci. 2000;12:2623-2633.
15. Amin-Hanjani S, Stagliano NE, Yamada M, Huang PL, Liao JK, Moskowitz MA. Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice. Stroke. 2001;32:980-986.
16. Sironi L, Cimino M, Guerrini U, Calvio AM, Lodetti B, Asdente M, Balduini W, Paoletti R, Tremoli E. Treatment with statins after induction of focal ischemia in rats reduces the extent of brain damage. Arterioscler Thromb Vasc Biol. 2003;23:322-327.
17. Aden U, Dahlberg V, Fredholm BB, Lai LJ, Chen Z, Bjelke B. MRI evaluation and functional assessment of brain injury after hypoxic ischemia in neonatal mice. Stroke. 2002;33:1405-1410.
18. Liao JK. Statins and ischemic stroke. Atheroscler Suppl. 2002;3:21-25.
19. Szaflarski J, Burtrum D, Silverstein FS. Cerebral hypoxia-ischemia stimulates cytokine gene expression in perinatal rats. Stroke. 1995;26:1093-1100.
20. Martin D, Chinookoswong N, Miller G. The interleukin-1 receptor antagonist (rhil-1ra) protects against cerebral infarction in a rat model of hypoxia-ischemia. Exp Neurol. 1994;130:362-367.
21. Pruefer D, Makowski J, Schnell M, Buerke U, Dahm M, Oelert H, Sibelius U, Grandel U, Grimminger F, Seeger W, et al. Simvastatin inhibits inflammatory properties of Staphylococcus aureus α-toxin. Circulation. 2002;106:2104-2110.