PMID- 10506522 OWN - NLM STAT- MEDLINE DCOM- 19991119 LR - 20220318 IS - 0014-4886 (Print) IS - 0014-4886 (Linking) VI - 159 IP - 2 DP - 1999 Oct TI - Brain-derived neurotrophic factor improves long-term potentiation and cognitive functions after transient forebrain ischemia in the rat. PG - 511-9 AB - We investigated the effect of brain-derived neurotrophic factor (BDNF) on hippocampal long-term potentiation (LTP) and cognitive functions after global cerebral ischemia in the rat. After four-vessel occlusion, BDNF was administered via an osmotic minipump continuously over 14 days intracerebroventricularly. Electrophysiological experiments were performed 14 days after cerebral ischemia. Test stimuli and tetanization were delivered to the Schaffer collaterals of the hippocampus and field excitatory postsynaptic potentials (fEPSP) were recorded in the CA1 region. Cognitive impairment was analyzed 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 consistantly induced after delivering a tetanus (increase of initial slope of fEPSP to 173 +/- 12% of baseline; n = 6). After transient forebrain ischemia LTP could not be induced (117 +/- 4% of baseline; n = 7). In ischemic animals treated with BDNF, LTP could be induced (168 +/- 28% of baseline; n = 8). Transient forebrain ischemia resulted in a significant decrease in spatial discrimination performance but not of associative memory. The ratios for working memory (WM) and reference memory (RM) 15 days after ischemia were lower in the ischemic rats (n = 10) than in the sham-operated control animals (n = 10; WM: 22 +/- 6 vs 72 +/- 7; RM: 30 +/- 7 vs 72 +/- 5). Postischemic intracerebroventricular BDNF infusion increased both WM (63 +/- 4; n = 10) and RM (58 +/- 5; n = 10). The spontaneous locomotor activity did not differ significantly in the three groups. These data indicate a protective effect of BDNF for synaptic transmission and cognitive functions after transient forebrain ischemia. CI - Copyright 1999 Academic Press. FAU - Kiprianova, I AU - Kiprianova I AD - Department of Neurology, University of Heidelberg, Heidelberg, D-69120, Germany. FAU - Sandkuhler, J AU - Sandkuhler J FAU - Schwab, S AU - Schwab S FAU - Hoyer, S AU - Hoyer S FAU - Spranger, M AU - Spranger M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Avoidance Learning/drug effects/physiology MH - Brain-Derived Neurotrophic Factor/administration & dosage/*pharmacology MH - Cerebral Ventricles/drug effects/physiology/physiopathology MH - Cognition/drug effects/*physiology MH - Electric Stimulation MH - Excitatory Postsynaptic Potentials/drug effects/physiology MH - Infusions, Parenteral MH - Ischemic Attack, Transient/drug therapy/*physiopathology/*psychology MH - Long-Term Potentiation/drug effects/*physiology MH - Male MH - Memory/drug effects/physiology MH - Prosencephalon/drug effects/*physiopathology MH - Pyramidal Cells/drug effects/*physiology MH - Rats MH - Rats, Wistar MH - Reference Values EDAT- 1999/10/03 00:00 MHDA- 1999/10/03 00:01 CRDT- 1999/10/03 00:00 PHST- 1999/10/03 00:00 [pubmed] PHST- 1999/10/03 00:01 [medline] PHST- 1999/10/03 00:00 [entrez] AID - S0014-4886(99)97109-1 [pii] AID - 10.1006/exnr.1999.7109 [doi] PST - ppublish SO - Exp Neurol. 1999 Oct;159(2):511-9. doi: 10.1006/exnr.1999.7109.