Bacteremia causes hippocampal apoptosis in experimental pneumococcal meningitis

Østergaard, Christian Richter; Leib, Stephen L.; Rowland, Ian J.; Brandt, Christian

doi:10.1186/1471-2334-10-1

Cited by 170 publications

(191 citation statements)

References 20 publications

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“…The neuropathologic changes in the disease model of BM show important similarities to human cases of meningitis and are characterized by focal tissue injury in the cortex, the hippocampus, and the inner ear. In the hippocampus and specifically the DG, histomorphologic analysis documented the occurrence of apoptosis scattered along the subgranular zone of the DG [14,20,44]. Similar to the in vitro results, after transplantation into rats 1 week after experimental pneumococcal infection, hippocampal cells migrated into the subgranular zone of the injured DG.…”

Section: Discussionsupporting

confidence: 64%

Grafted Neuronal Precursor Cells Differentiate and Integrate in Injured Hippocampus in Experimental Pneumococcal Meningitis

Höfer¹,

Magloire

Streit

et al. 2012

Stem Cells

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Bacterial meningitis (BM) frequently causes persisting neurofunctional sequelae. Autopsy studies in patients dying from BM show characteristic apoptotic brain injury to the stem cell niche in the subgranular zone of the hippocampal dentate gyrus (DG), and this form of brain damage is associated with learning and memory deficits in experimental BM. With an eye to potential regenerative therapies, the survival, migration, and differentiation of neuronal precursor cells (NPCs) were evaluated after engraftment into the injured hippocampus in vitro and in vivo in an infant rat model of pneumococcal meningitis. Green fluorescent protein (GFP)-expressing NPCs were grafted into the DG of organotypic hippocampal slice cultures injured by challenge with live Streptococcus pneumoniae. Seven days after engraftment, NPCs had migrated from the site of injection into the injured granular layer of the DG and electro-functionally integrated into the hippocampal network. In vivo, GFP-expressing NPCs migrated within 1 week from the injection site in the hilus region to the injured granular layer of the hippocampal DG and showed neuronal differentiation at 2 and 4 weeks after transplantation. Hippocampal injury induced by BM guides grafted NPCs to the area of brain damage and provides a microenvironment for neuronal differentiation and functional integration. Disclosure of potential conflicts of interest is found at the end of this article.

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Section: Discussionsupporting

confidence: 64%

Grafted Neuronal Precursor Cells Differentiate and Integrate in Injured Hippocampus in Experimental Pneumococcal Meningitis

Höfer¹,

Magloire

Streit

et al. 2012

Stem Cells

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“…Recent findings with experimental animal models have suggested that neuronal damage may also be caused by pneumococcal growth outside the CNS compartment (365). Mice exposed intravascularly to purified PCW developed hippocampal apoptosis at 6 h postinoculation, an effect that was not reproduced in TLR2-or NOD2-deficient mice and was limited in mice overexpressing .…”

Section: Sepsis and Hippocampal Damagementioning

confidence: 99%

Pathogenesis and Pathophysiology of Pneumococcal Meningitis

et al. 2011

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SUMMARY Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae , which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy.

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“…In Africa, the incidence was 46 per 100,000 and the CFR jumped to an alarming 67%. Half of the fatal cases of Hib meningitis worldwide (78,300) occurred in Africa (34,600). 9 In a similar survey for pneumococcal meningitis in children less than five years of age, the global incidence rate was 17 per 100,000 (38 for Africa) and the CFR was 59% (73% for Africa).…”

mentioning

confidence: 99%