Transient changes of brain-derived neurotrophic factor (BDNF) mRNA expression in hippocampus during moderate ischemia induced by chronic bilateral common carotid artery occlusions in the rat

Chronic bilateral common carotid artery occlusion (BCCAO) induces moderate ischemia (oligemia) in the rat forebrain in the absence of overt neuronal d amage. In situ hybridization for brain-derived neurotrophic factor (BDNF) m RNA was used to search for a molecular response to moderate ischemia. BDNF mRNA was significantly increased in the hippocampal granule cells at 6 h of occlusion (ANOVA, Tukey test P <0.05). At 1, 7 and 14 days BDNF mRNA level s returned to control levels. The frequency of BDNF gene expression at 6 h was 83%, which was significantly higher than the 7% incidence of histologic al injury in the hippocampus (Fisher's exact test, P <0.002). Cerebral bloo d flow was reduced to 75% of control levels in the hippocampus after I week of BCCAO when measured with the autoradiographic method. Measurements of t issue flow with a microprobe for laser Doppler flow excluded decreases into the ischemic range during the period when elevated gene expression was obs erved. Prolonged moderate ischemia (oligemia) is a sufficient stimulus for BDNF gene expression in the hippocampus. These molecular studies provide di rect evidence for an involvement of the hippocampus in the BCCAO model. (C) 2001 Elsevier Science BY All rights reserved.