Brain-derived neurotrophic factor improves long-term potentiation and cognitive functions after transient forebrain ischemia in the rat

We investigated the effect of brain-derived neurotrophic factor (BDNF) on h ippocampal long-term potentiation (LTP) and cognitive functions after globa l cerebral ischemia in the rat. After four-vessel occlusion, BDNF was admin istered via an osmotic minipump continuously over 14 days intracerebroventr icularly. Electrophysioloscal experiments were performed 14 days after cere bral ischemia, Test stimuli and tetanization were delivered to the Schaffer collaterals of the hippocampus and field excitatory postsynaptic potential s (fEPSP) were recorded in the CA1 region. Cognitive impairment was analyze d repeatedly with a passive avoidance test, a hole-board test, and with an activity center on the same animal. In sham-operated animals, LTP was consi stantly induced after delivering a tetanus (increase of initial slope of fE PSP to 173 +/- 12% of baseline; n = 6). After transient forebrain ischemia LTP could not be induced (117 +/- 4% of baseline; n = 7), In ischemic anima ls treated with BDNF, LTP could be induced (168 +/- 28% of baseline; n = 8) . Transient forebrain ischemia resulted in a significant decrease in spatia l discrimination performance but not of associative memory. The ratios for working memory (WM) and reference memory (RIM) 15 days after ischemia were lower in the ischemic rats (n = 10) than in the sham-operated control anima ls (n = 10; WM: 22 +/- 6 vs 72 +/- 7; RM: 30 +/- 7 vs 72 +/- 5). Postischem ic intracerebroventricular BDNF infusion increased both WM (63 +/- 4; n = 1 0) and RM (58 +/- 5; n = 10). The spontaneous locomotor activity did not di ffer significantly in the three groups. These data indicate a protective ef fect of BDNF for synaptic transmission and cognitive functions after transi ent forebrain ischemia. (C) 1999 Academic Press.