Cortical Gene Expression after Spreading Depression

Cortical spreading depression (SD) plays an important role during migraine aura and stroke. In focal cerebral ischemia, peri-infarct depolarizations (PD), a phenomenon consistent with SD in normal brain, cause expansion of the infarct size within the ischemic penumbra. Otherwise, preconditioning with SD can modulate the outcome of an ischemic injury: when SD occurs more than a day before ischemia, injury is reduced. A number of previous studies showed that gene expression changed after experimentally induced stroke. The aim of this study was to investigate the impact of SDs on the pathophysiological processes after ischemic brain injury at the gene expression level. 7±2 repetitive SDs were induced in rat occipital cortex by topical application of 3 M KCl. Control animals were treated with 3 M NaCl which does not induce SDs. Gene expression has been analyzed in ipsilateral hindlimb cortex 3h, 24h, 7d and 30d after first KCl/NaCl application using Affymetrix RAE230 arrays. Time-dependent gene expression profiles showed highest differential gene expression at 3h, decreasing successively at later time points. Some of the 3h and 24h data are in agreement with previously published PCR studies of single genes after SD and studies concerning post-stroke gene expression changes: among others immediate early genes, genes for neurotrophic factors and their receptors, stress response proteins and genes involved in inflammatory response are regulated. Surprisingly, we found various genes that are differently expressed 30d after SD, indicating an influence of PD on delayed processes in non-infarcted ipsilateral cortex. At present the impact of this late differential gene expression is ambiguous. Nevertheless, one possible mechanism may be an influence on cortical reorganization. For further evaluation of the microarray data a representative selection of genes will be verified by real-time RT-PCR.