Effect of Cortical Spreading Depression on the Levels of mRNA Coding for Putative Neuroprotective Proteins in Rat Brain

Abstract

Previous studies have demonstrated that cortical spreading depression (CSD) induces neuronal tolerance to a subsequent episode of ischemia. The objective of the present investigation was to determine whether CSD alters levels of mRNA coding for putative neuroprotective proteins. Unilateral CSD was evoked in male Wistar rats by applying 2 mol/L KCl over the frontal cortex for 2 hours. After recovery for 0, 2, or 24 hours, levels of several mRNA coding for neuroprotective proteins were measured bilaterally in parietal cortex using Northern blot analysis. Levels of c-fos mRNA and brain-derived neurotrophic factor (BDNF) mRNA were markedly elevated at 0 and 2 hours, but not 24 hours after CSD. Tissue plasminogen activator (tPA) mRNA levels were also significantly increased at 0 and 2 hours, but not 24 hours after CSD. Levels of the 72-kDa heat-shock protein (hsp72) mRNA were not significantly increased by CSD, except for a small elevation (20%) at 2 hours recovery. Levels of the 73-kDa heat-shock cognate (hsc73) mRNA were slightly, but significantly, increased at 2 and 24 hours of recovery. Finally, levels of mRNA for protease nexin-1 and glutamine synthetase were not significantly altered by CSD at any time studied. The current results support the hypothesis that neuronal tolerance to ischemia after CSD may be mediated by increased expression of FOS, BDNF, or tPA, but not by increased expression of hsp72, hsc73, nexin-1, or glutamine synthetase.

Induction of Tolerance to Focal Ischemia in Rat Brain: Dissociation between Cortical Lesioning and Spreading Depression

“…The occurrence of CSD at later times is also unlikely because of the absence of changes in gene expression that are normally associated with CSD. Previous studies have shown that CSD triggers a robust elevation of c-fos mRNA in the ipsilateral cortex (Karikó et al, 1998;Rangel et al, 2001). In the present study, changes in c-fos mRNA or BDNF mRNA levels were not detected at 2 hours or 24 hours after application of 5-mol/L NaCl.…”

“…Physiologic saline (0.15-mol/L NaCl) was applied in a similar fashion in controls (n ‫ס‬ 8). The occurrence of CSD was monitored through the thinned skull over the ipsilateral cortex (2 mm caudal to bregma, 4 mm lateral to the midline) using laser-Doppler flowmetry as described previously (Karikó et al, 1998;Rangel et al, 2001). …”

Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

“…Following focal ischemia, multiple episodes of cortical spreading depression have been demonstrated in the penumbra as well as more remote regions of the brain (Back, 1998;Dietrich et al, 2000;Hossman, 1996). These propogating waves are caused by intracellular calcium that depolarizes cells and cause metabolic stress and the induction of a variety of genes and proteins in areas away from the infarct (Kariko et al, 1998).…”

Neural Activity-Dependent Cellular Proliferation in the Rat Cerebral Cortex

“…The cellular proliferation observed here is thought to be induced by several cytokines or growth factors, as SD is known to induce production of basic fibroblast growth factor [22], tissue plasminogen activator [16], brain-derived neurotrophic factor [7,16,22], interleukin 1b, tumor necrosis factor-a [15], and prostaglandins [18]. The substances mediating neural activity and cellular proliferation in the present animal model remain to be identified.…”