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(Stroke. 2003;34:2710.)
© 2003 American Heart Association, Inc.

Original Contributions

Intraventricular Infusion of TrkB-Fc Fusion Protein Promotes Ischemia-Induced Neurogenesis in Adult Rat Dentate Gyrus

From the Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, Lund, Sweden.

Correspondence to Zaal Kokaia, Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital BMC A11, SE-221 84 Lund, Sweden. E-mail zaal.kokaia{at}neurol.lu.se

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.

Key Words: brain-derived neurotrophic factor • cerebral ischemia, global • hippocampus • neurons • stroke • rats

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