Chih-Zen Chang, Shu-Chuan Wu, Chih-Lung Lin and Aij-Lie Kwan
Background: Increased evidence has disclosed early brain injury (EBI) might determine the outcome of patients
suffering from aneurismal subarachnoid hemorrhage (SAH). This study is of interest to examine the efficacy of
parecoxib, a cyclooxygenase-2(COX-2) inhibitor, on SAH-induced EBI.
Methods: The rodent SAH model was employed. 500/1000/2000ug/kg/day parecoxib was administered via
osmotic mini-pump. CSF samples were collected to examine IL-1β, IL-6, IL-8 and TNF-α. Cerebral cortex was
harvested for C-Jun N-terminal kinase (cJNK), NMDARs (western blot), B-cell lymphoma 2 (Bcl-2), caspases (rt-
PCR) measurement.
Results: Parecoxib dose-dependently reduced the bio-expression of cJNK when compared with the SAH groups.
No significant differences were found in the levels of IL-8 among the experimental groups. The levels of IL-1β, IL-6
and TNF-α were increased in animals subjected to SAH, compared with healthy controls, but not in the medium- and
high-dose parecoxib treatment group. Moreover, the levels of TNF-α in the SAH-only and SAH-plus vehicle groups
were significantly elevated, and treatment with parecoxib (1000ug/kg) reduced the level of healthy controls. Cleaved
caspase-3 and -9a were both significantly reduced in 2000ug/kg parecoxib treatment groups. Likewise, NMDAR-2a
was significantly suppressed in parecoxib treatment SAH groups (p <0.01).
Conclusion: Treatment with parecoxib exerts its neuroprotective effect through the dual effect of inhibiting cJNKactivated
neuro-inflammation and reduced mitochondrion-related caspase-9a expression. Besides, parecoxib
decreased CSF levels of TNF-α and IL-1β, which contributes to the anti-delayed vasoconstriction effect. This study
lends credence to support the COX-2 inhibitor could attenuate SAH-induced EBI.