J Neuroimmunol. 2016 May 15;294:46-55. doi: 10.1016/j.jneuroim.2016.03.014. Epub 2016 Apr 6.

Exogenous BDNF increases neurogenesis in the hippocampus in experimental Streptococcus pneumoniaemeningitis.

Lian D1, He D1, Wu J1, Liu Y2, Zhu M3, Sun J3, Chen F2, Li L4.

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Despite the effective use of antibiotics, occurrences of mortality and neurological sequelae following Streptococcus pneumoniaemeningitis remain high.


We investigated the neurogenesis of endogenous neural stem cells (NSCs) after inoculation with exogenous brain-derived neurotrophic factor (BDNF) in the hippocampus dentate gyrus following experimental S. pneumoniae meningitis using a double-labeling immunofluorescence analysis with 5-bromo-2'-deoxyuridine (BrdU), Nestin, DCX and NeuN.


Our results showed that 7days after inoculation, the number of BrdU & Nestin co-labeled cells increased in the hippocampus in meningitis rats compared with control rats (p<0.05). But the number of DCX-positive cells decreased in the dentate gyrus of infected rats treated with saline (p<0.05). However, these cell numbers returned to close to normal-control levels in infected rats treated with BDNF (p>0.05). After treatment with exogenous BDNF, the number of BrdU & Nestin co-labeled cells increased in the hippocampus in both the meningitis rats and normal control rats (p<0.05), but this increase was more significant in the former (p<0.05). We found that the percentage of BrdU & DCX/BrdU co-labeled cells increased in infected rats treated with BDNF both 7days and 14days after inoculation in a greater proportion compared to other groups (p<0.05). No significant differences were found in the percentage of BrdU & NeuN/BrdU 28days after inoculation among all of the groups (p>0.05).


Our findings suggest that S. pneumoniae meningitis activates the proliferation of endogenous NSCs, but impairs their early differentiation. Administration of exogenous BDNF might improve the neurogenesis of endogenous NSCs in the hippocampus and may provide a promising therapy after bacterial meningitis.

Copyright © 2016 Elsevier B.V. All rights reserved.


Brain-derived neurotrophic factor; Endogenous neurogenesis; Neural stem cells; Streptococcus pneumoniae meningitis

PMID: 27138098 [PubMed - in process]