THE ROLE OF EXTRACELLULAR IONIC CHANGES IN UP-REGULATING THE MESSENGER-RNA FOR GLIAL FIBRILLARY ACIDIC PROTEIN FOLLOWING SPREADING DEPRESSION

While spreading depression has been shown to be a powerful stimulus in upregulating glial fibrillary acidic protein (GFAP) mRNA expression, the specific physiological signal underlying the upregulation is unkno wn. During spreading depression, extracellular ionic concentrations ar e altered markedly. The present study evaluates the role of these chan ges in extracellular ionic concentrations as potential signals influen cing GFAP mRNA expression. Gel foam pledgets saturated with artificial cerebrospinal fluid (CSF) solutions in which [Na+], [Ca2+], [K+] and [H+] were altered one at a time to match concentrations seen in spread ing depression were applied to exposed parietal cortex for one hour. D ot blot and in situ hybridization techniques were used to evaluate GFA P mRNA levels. We found that CSF containing 60 mM KCl produced a drama tic upregulation of GFAP mRNA levels throughout the cerebral cortex of the ipsilateral hemisphere without causing detectable tissue damage. The pattern and time course of the change were similar to those follow ing application of 3 M KCl. Alteration of other ionic species did not affect GFAP mRNA levels. However, the upregulation of GFAP mRNA was no t likely due directly to the increased [K+], but rather to the spreadi ng depression that the elevated [K+] induced. This was demonstrated by the finding that the upregulation in GFAP mRNA induced by the potassi um exposure was totally blocked by prior administration of MK-801, an NMDA antagonist that blocks spreading depression. These results demons trate that an upregulation in GFAP mRNA can occur in the absence of de generation debris and that the initiating events can be related to phy siological changes, but that changes in extracellular ionic concentrat ions are not the likely molecular signals underlying the upregulation.