This Article Full Text Full Text (PDF) All Versions of this Article: 39/11/3064    most recent STROKEAHA.108.518076v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Urbach, A. Articles by Witte, O. W. Search for Related Content PubMed PubMed Citation Articles by Urbach, A. Articles by Witte, O. W. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Animal models of human disease

(Stroke. 2008;39:3064.)
© 2008 American Heart Association, Inc.

Original Contributions

Induction of Neurogenesis in the Adult Dentate Gyrus by Cortical Spreading Depression

From the Department of Neurology, Friedrich-Schiller-University, Jena, Germany.

Correspondence to Anja Urbach, Department of Neurology, Friedrich-Schiller-University, Erlanger Allee 101/FZL, 07747 Jena, Germany. E-mail anja.urbach{at}med.uni-jena.de

Background and Purpose— Spreading depression (SD) is an epiphenomenon of neurological disorders, like stroke or traumatic brain injury. These diseases have been associated with an increased neurogenesis in the adult rodent dentate gyrus. Such proliferative activity can also be induced by conditions that—like SD—coincide with a disturbed neuronal excitability, eg, epilepsy. Thus we hypothesized that SD might likewise influence hippocampal neurogenesis and potentially act as mediator of injury-induced neurogenesis.

Methods— Repetitive cortical SD were induced by epidural application of 3 mol/L KCl. At different time points thereafter dentate gyrus neurogenesis was investigated by means of intraperitoneal bromodeoxyuridine injections and immunocytochemistry. Spatial learning and memory was tested in a Morris water maze.

Results— Cortical SD significantly increased proliferative activity in the ipsilateral subgranular zone on days 2 and 4. We detected about 280% more newborn cells in the dentate gyrus of rats that received bromodeoxyuridine during the first week after SD and were allowed to recover for 6 weeks. Most of these cells expressed the mature neuronal marker NeuN. The mitogenic action of SD was suppressed by systemic administration of the NMDA receptor antagonist MK-801. Behavioral performance of SD animals in the Morris water maze did not improve significantly.

Conclusions— From our data we postulate that the increased dentate gyrus neurogenesis observed after brain injury may at least partly be mediated by SD-like epiphenomena. Furthermore they indicate that even a strongly enhanced dentate gyrus neurogenesis may occur without significant improvements in hippocampus-dependent spatial learning and memory.

Key Words: spreading depression • neurogenesis • dentate gyrus • cognition

This article has been cited by other articles:

				J.-H. Xue, H. Yanamoto, Y. Nakajo, N. Tohnai, Y. Nakano, T. Hori, K. Iihara, and S. Miyamoto Induced Spreading Depression Evokes Cell Division of Astrocytes in the Subpial Zone, Generating Neural Precursor-Like Cells and New Immature Neurons in the Adult Cerebral Cortex Stroke, November 1, 2009; 40(11): e606 - e613. [Abstract] [Full Text] [PDF]