Bilateral induction of the S-100A9 gene in response to spreading depression is modulated by the cyclooxygenase-2 activity

Cyclooxygenase-2 (COX-2) was reported to be induced in the infarcted human brain. Spreading depression (SD) is thought to play a role in this induction. In this study, we correlated the expression of SD-associated genes with COX-2 production in brains after SD. Rats were divided into 3 groups: rats that did not undergo SD (group I saline controls, n = 7), rats that underwent unilateral SD as a result of KCl application (group II, n = 9), and rats that were pretreated with the selective COX-2 inhibitor, JTE-522 3 h before the induction of SD (group III, n = 7). The expression of the SD-associated genes, S-100A9, and mitogen-activated proteinkinase phosphatase (cpg21) was analyzed 2 h later using a cDNA array. In group II, COX-2 and cpg21 mRNA expression, as determined by RT-PCR, were significantly upregulated in the hemisphere undergoing SD. While the expression of S-100A9 mRNA was bilaterally upregulated in these animals, this expression was significantly reduced in group III, and was accompanied by reduced bilateral production of PGE2. Thus, the bilateral induction of expression of the S-100A9 gene in response to SD was associated with COX-2 activation.