Bilateral ischemic tolerance of rat hippocampus induced by prior unilateral transient focal ischemia: Relationship to c-fos mRNA expression

The purpose of this study was to determine whether transient unilateral (2 h) middle cerebral artery occlusion (MCAo) is capable of inducing bilateral ischemic tolerance in hippocampal CA1 neurons when temporary bilateral forebrain ischemia by two-vessel occlusion (2VO) is carried out 3 days later, and to explore the relationship of this tolerance to the regional expression of c-fos and hsp-70 mRNA. Rats were sacrificed 4 days after 2VO, and normal-appearing neurons in CA1 subregions were counted. Rats subjected to MCAo and 2VO showed significant protection of CA1 neurons in both hippocampi, whereas rats which underwent sham MCAo and 2VO typically had severe bilateral destruction of CA1 neurons (normal neuron counts, ipsilateral medial CA1: 59.8 ± 7.2 vs 16.6 ± 7.8 (mean ± s.e.m.); middle CA1: 50.0 ± 4.7 vs 16.0 ± 8.8; lateral CA1: 43.5 ± 5.7 vs 13.8 ± 6.3; contralateral, medial CA1: 52.3 ± 6.3 vs 17.0 ± 6.4; middle CA1: 43.3 ± 4.7 vs 19.8 ± 8.1; lateral CA1: 45.5 ± 4.6 vs 26.0 ± 10.3, respectively). This neuronal tolerance was preceded by the early bilateral induction of c-fos mRNA, which may in turn lead to expression of critical target genes that promote cell recovery.