Preconditioning with pitavastatin, an HMG-CoA reductase inhibitor, attenuates C-Jun N-terminal kinase activation in experimental subarachnoid hemorrhage-induced apoptosis.

Abstract:

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.

journal_name

Acta Neurochir (Wien)

journal_title

Acta neurochirurgica

authors

Chang CZ,Wu SC,Kwan AL,Lin CL

doi

10.1007/s00701-015-2399-3

subject

Has Abstract

pub_date

2015-06-01 00:00:00

pages

1031-41; discussion 1041

issue

6

eissn

0001-6268

issn

0942-0940

journal_volume

157

pub_type

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