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Updated: Jul 14, 2026
Assessment of Dendritic Arborization in the Dentate Gyrus of the Hippocampal Region in Mice
Published on: March 31, 2015
Pneumococcal cell wall-induced meningitis impairs adult hippocampal neurogenesis
Olaf Hoffmann1, Cordula Mahrhofer, Nina Rueter
1Department of Cell Biology, Center for Anatomy, Charité--Universitaetsmedizin Berlin, Schumannstr. 20/21, 10117 Berlin, Germany.
Abstract:
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.
Insights
Bacterial meningitis causes brain damage and impairs neurogenesis. Inhibiting inducible nitric oxide synthase (iNOS) restored this crucial brain repair mechanism in mice, suggesting new therapeutic targets for meningitis recovery.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Bacterial meningitis is a leading cause of neuronal loss in the hippocampus.
- Adult hippocampal neurogenesis, a repair process, is often insufficient after meningitis, leading to long-term deficits.
- The impact of transient central nervous system inflammation on adult neurogenesis requires further investigation.
Purpose of the Study:
- To investigate the effects of nonreplicative bacterial meningitis on adult hippocampal neurogenesis in a mouse model.
- To identify the mechanisms by which inflammation suppresses neurogenesis.
- To evaluate the therapeutic potential of targeting specific inflammatory pathways to restore neurogenesis.
Main Methods:
- Induction of experimental meningitis in mice using a nonreplicative bacterial model.
- Assessment of neuronal loss, hippocampal volume, and neurogenesis markers (proliferation and differentiation).
- Immunohistochemical analysis for inducible nitric oxide synthase (iNOS) in microglia.
- Pharmacological inhibition of iNOS using N6-(1-iminoethyl)-L-lysine.
Main Results:
- Experimental meningitis led to significant neuronal loss, reduced dentate gyrus volume, and suppressed neurogenesis lasting weeks post-insult.
- Prominent iNOS expression was observed in microglia within nonproliferating regions of the hippocampus.
- Treatment with an iNOS inhibitor successfully restored adult neurogenesis in mice with experimental meningitis.
Conclusions:
- Transient intracranial inflammation during meningitis actively suppresses adult hippocampal neurogenesis by affecting both cell proliferation and neuronal differentiation.
- Inducible nitric oxide synthase (iNOS) plays a critical role in mediating this inflammatory suppression of neurogenesis.
- Targeting iNOS presents a promising therapeutic strategy to enhance brain repair and potentially improve cognitive outcomes following bacterial meningitis.
