Di Lian1, Dake He1, Jing Wu1, Ying Liu2, Mingjie Zhu3, Jiaming Sun3, Feng Chen2, Ling Li4. 1. Department of Pediatric Neurology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China. 2. Department of Clinical Laboratory, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China. 3. Department of Pathology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China. 4. Department of Pediatric Neurology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China. Electronic address: linglidoctor@163.com.
Abstract
BACKGROUND: Despite the effective use of antibiotics, occurrences of mortality and neurological sequelae following Streptococcus pneumoniae meningitis remain high. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
BACKGROUND: Despite the effective use of antibiotics, occurrences of mortality and neurological sequelae following Streptococcus pneumoniae meningitis remain high. METHODS: 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. RESULTS: Our results showed that 7days after inoculation, the number of BrdU & Nestin co-labeled cells increased in the hippocampus in meningitisrats 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 meningitisrats 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). CONCLUSION: 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.
Authors: Nikolay Mehterov; Danail Minchev; Maria Gevezova; Victoria Sarafian; Michael Maes Journal: Mol Neurobiol Date: 2022-06-03 Impact factor: 5.682