PMID- 14563966 OWN - NLM STAT- MEDLINE DCOM- 20031125 LR - 20161122 IS - 1524-4628 (Electronic) IS - 0039-2499 (Linking) VI - 34 IP - 11 DP - 2003 Nov TI - Intraventricular infusion of TrkB-Fc fusion protein promotes ischemia-induced neurogenesis in adult rat dentate gyrus. PG - 2710-5 AB - BACKGROUND AND PURPOSE: We have previously shown that delivery of brain-derived neurotrophic factor (BDNF) through direct intrahippocampal gene transduction with a viral vector suppresses the formation of new dentate granule cells triggered by global forebrain ischemia. Here, we investigated whether inhibition of endogenous BDNF alters ischemia-induced neurogenesis in the dentate gyrus. METHODS: Rats were subjected to 30 minutes of global forebrain ischemia and then received intraventricular infusion of either the BDNF scavenger, TrkB-Fc fusion protein, or control Hu-Fc for 2 weeks. In parallel, all animals were injected intraperitoneally with the mitosis marker 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdU). Animals were killed at 2 or 6 weeks after the ischemic insult, and neurogenesis was then assessed immunocytochemically with epifluorescence or confocal microscopy. RESULTS: Infusion of TrkB-Fc fusion protein gave rise to elevated numbers of ischemia-generated new neurons, double-labeled with BrdU and the early neuronal marker Hu or the mature neuronal marker NeuN, in the dentate subgranular zone and granule cell layer at 2 and 6 weeks after the insult. CONCLUSIONS: Our findings provide evidence that endogenous BDNF counteracts neuronal differentiation, but not cell proliferation or survival, in ischemia-induced dentate gyrus neurogenesis. FAU - Gustafsson, Elin AU - Gustafsson E AD - Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, Lund, Sweden. FAU - Lindvall, Olle AU - Lindvall O FAU - Kokaia, Zaal AU - Kokaia Z LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20031016 PL - United States TA - Stroke JT - Stroke JID - 0235266 RN - 0 (Antigens, Differentiation) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - EC 2.7.10.1 (Receptor, trkB) RN - G34N38R2N1 (Bromodeoxyuridine) SB - IM MH - Animals MH - Antigens, Differentiation/biosynthesis MH - Brain Ischemia/*physiopathology MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Bromodeoxyuridine MH - Cell Differentiation/drug effects MH - Cell Division/drug effects MH - Dentate Gyrus/cytology/*drug effects/physiopathology MH - Disease Models, Animal MH - Immunoglobulin Fc Fragments/*genetics MH - Injections, Intraventricular MH - Male MH - Neurons/cytology/*drug effects/metabolism MH - Prosencephalon/blood supply/physiopathology MH - Rats MH - Rats, Wistar MH - Receptor, trkB/*genetics MH - Recombinant Fusion Proteins/administration & dosage/*pharmacology EDAT- 2003/10/18 05:00 MHDA- 2003/12/03 05:00 CRDT- 2003/10/18 05:00 PHST- 2003/10/18 05:00 [pubmed] PHST- 2003/12/03 05:00 [medline] PHST- 2003/10/18 05:00 [entrez] AID - 01.STR.0000096025.35225.36 [pii] AID - 10.1161/01.STR.0000096025.35225.36 [doi] PST - ppublish SO - Stroke. 2003 Nov;34(11):2710-5. doi: 10.1161/01.STR.0000096025.35225.36. Epub 2003 Oct 16.