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Infection and Immunity, September 2007, p. 4289-4297, Vol. 75, No. 9
0019-9567/07/$08.00+0     doi:10.1128/IAI.01679-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Pneumococcal Cell Wall-Induced Meningitis Impairs Adult Hippocampal Neurogenesis{triangledown}

Olaf Hoffmann,1 Cordula Mahrhofer,1 Nina Rueter,1 Dorette Freyer,1 Bettina Bert,3 Heidrun Fink,3 and Joerg R. Weber1,2*

Department of Neurology,1 Department of Cell Biology, Center for Anatomy, Charité-Universitaetsmedizin Berlin, Berlin, Germany,2 Institute of Pharmacology and Toxicology, Veterinary Medicine, Freie Universität, Berlin, Germany3

Received 20 October 2006/ Returned for modification 19 December 2006/ Accepted 13 June 2007

Bacterial meningitis is a major infectious cause of neuronal degeneration in the hippocampus. Neurogenesis, a continuous process in the adult hippocampus, could ameliorate such loss. Yet the high rate of sequelae from meningitis suggests that this repair mechanism is inefficient. Here we used a mouse model of nonreplicative bacterial meningitis to determine the impact of transient intracranial inflammation on adult neurogenesis. Experimental meningitis resulted in a net loss of neurons, diminished volume, and impaired neurogenesis in the dentate gyrus for weeks following recovery from the insult. Inducible nitric oxide synthase (iNOS) immunoreactivity was prominent in microglia in nonproliferating areas of the dentate gyrus and hilus region after meningitis induction. Treatment with the specific iNOS inhibitor N6-(1-iminoethyl)-L-lysine restored neurogenesis in experimental meningitis. These data suggest that local central nervous system inflammation in and of itself suppresses adult neurogenesis by affecting both proliferation and neuronal differentiation. Repair of cognitive dysfunction following meningitis could be improved by intervention to interrupt these actively suppressive effects.

* Corresponding author. Mailing address: Department of Cell Biology, Center for Anatomy, Charité-Universitaetsmedizin Berlin, Schumannstr. 20/21, 10117 Berlin, Germany. Phone: 49 30 450 528002. Fax: 49 30 450 528902. E-mail: joerg.weber{at}charite.de

{triangledown} Published ahead of print on 25 June 2007.

Editor: J. N. Weiser

Infection and Immunity, September 2007, p. 4289-4297, Vol. 75, No. 9
0019-9567/07/$08.00+0     doi:10.1128/IAI.01679-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gerber, J., Tauber, S. C., Armbrecht, I., Schmidt, H., Bruck, W., Nau, R. (2009). Increased neuronal proliferation in human bacterial meningitis. Neurology 73: 1026-1032 [Abstract] [Full Text]  


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