Analysis of c-Fos and glial fibrillary acidic protein (GFAP) expression following topical application of potassium chloride (KCl) to the brain surface

Abstract

Application of high K + concentrations to a limited area of the brain surface is known to trigger spreading depression. We used this model to observe the response of cortical areas, distant to the exposed site, at the cellular level. Immunostaining of glial fibrillary acidic protein (GFAP) and of the proto-oncogene c-Fos was analyzed in brain sections at different times after K + application. Piriform and parietal cortices, as observed in coronal sections located 3 mm rostrally from the center of the stimulated area and ipsilateral to it, showed a dramatic increase in immunostaining for both markers. However, the time course for such increments was different. c-Fos protein(s) expression was high at 1.5 h and decreased at 24 h after K + exposure and c- fos mRNA expression correlated with the immunohistochemical results. At these initial times GFAP immunoreactivity was still low but began to rise between 2 and 7 days after treatment in exactly the same areas where c-Fos expression had been up-regulated. No significant effect, for either marker, was evident in the contralateral piriform or parietal cortices. In addition, we studied the effects of the NMDA antagonist MK-801 (4 mg/kg i.p.) on the expression of mRNA for GFAP and c- fos and demonstrated a marked reduction in the upregulation of these genes.