CORTICAL SPREADING DEPRESSION ACTIVATES TROPHIC FACTOR EXPRESSION, INNEURONS AND ASTROCYTES AND PROTECTS AGAINST SUBSEQUENT FOCAL BRAIN ISCHEMIA

We recently reported that cortical spreading depression (CSD), used to precondition rat brain, reduced cortical infarction volume resulting from focal cerebral ischemia by middle cerebral artery occlusion (MCAO ) 3 days later. The mechanisms underlying this protective effect by CS D remains to be explored. In this study, we confirm that CSD is neurop rotective when KCl is applied epidurally rather than intracortically. Neocortical infarct volume was 101.3 +/- 48.5 mm(3) and 45.3 +/- 44.1 mm(3) in the ham and CSD group, respectively (p < 0.05). Using image a nalysis, we identified the cortical region spared from infarction by t he prior CSD. We then determined the distribution of brain-derived neu rotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) mRNA and the time course of their expression in groups of animals treated with CSD and their controls. We also examined the response of astrocyt es to CSD using glial fibrillary acidic protein (GFAP) as a marker. In situ hybridization (done at 0, 3, 12, 24, 72 or 168 h after CSD) show ed significant elevation of BDNF mRNA in the cortex immediately after CSD in a distribution surrounding the spared cortex, while bFGF mRNA r ose 12 h after CSD and appeared more within the core of the ischemic r egion. Immunohistochemistry (done at 1, 3 or 7 days after CSD) demonst rated GFAP in the neocortex, with a peak at 3 days after CSD. Heat sho ck protein 72 (HSP72) expression was not affected by CSD. We concluded that upregulation of trophic factors and activation of glial cells ma y contribute to the neuroprotection induced by CSD. (C) 1998 Elsevier Science B.V. All rights reserved.