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The antidepressant fluoxetine protects the hippocampus from brain damage in experimental pneumococcal meningitis
F D Liechti1, D Grandgirard1, S L Leib2
1Neuroinfection Laboratory, Institute for Infectious Diseases, University of Bern, Friedbühlstrasse 51, CH-3010 Bern, Switzerland.
Background:
High mortality and morbidity rates are observed in patients with bacterial meningitis (BM) and urge for new adjuvant treatments in addition to standard antibiotic therapies. In BM the hippocampal dentate gyrus is injured by apoptosis while in cortical areas ischemic necrosis occurs. Experimental therapies aimed at reducing the inflammatory response and brain damage have successfully been evaluated in animal models of BM. Fluoxetine (FLX) is an anti-depressant of the selective serotonin reuptake inhibitors (SSRI) and was previously shown to be neuroprotective in vitro and in vivo. We therefore assessed the neuroprotective effect of FLX in experimental pneumococcal meningitis.
Methods:
Infant rats were infected intracisternally with live Streptococcus pneumoniae. Intraperitoneal treatment with FLX (10mgkg(-1)d(-1)) or an equal volume of NaCl was initiated 15min later. 18, 27, and 42h after infection, the animals were clinically (weight, clinical score, mortality) evaluated and subject to a cisternal puncture and inflammatory parameters (i.e., cyto-/chemokines, myeloperoxidase activity, matrix metalloproteinase concentrations) were measured in cerebrospinal fluid (CSF) samples. At 42h after infection, animals were sacrificed and the brains collected for histomorphometrical analysis of brain damage.
Results:
A significant lower number of animals treated with FLX showed relevant hippocampal apoptosis when compared to littermates (9/19 animals vs 18/23, P=0.038). A trend for less damage in cortical areas was observed in FLX-treated animals compared to controls (13/19 vs 13/23, P=ns). Clinical and inflammatory parameters were not affected by FLX treatment.
Conclusion:
A significant neuroprotective effect of FLX on the hippocampus was observed in acute pneumococcal meningitis in infant rats.
Insights
Fluoxetine (FLX) demonstrates neuroprotective effects in infant rats with pneumococcal meningitis, reducing hippocampal apoptosis. This selective serotonin reuptake inhibitor (SSRI) shows promise as an adjuvant therapy for bacterial meningitis.
Area of Science:
- Neuroscience
- Pharmacology
- Infectious Diseases
Background:
- Bacterial meningitis (BM) presents high mortality and morbidity, necessitating novel adjuvant treatments.
- Hippocampal apoptosis and cortical ischemic necrosis are key pathological features of BM.
- Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine (FLX) have demonstrated neuroprotective properties.
Purpose of the Study:
- To evaluate the neuroprotective potential of fluoxetine (FLX) in an experimental model of pneumococcal meningitis.
- To assess the impact of FLX on brain damage, specifically hippocampal apoptosis and cortical necrosis, in infant rats.
Main Methods:
- Infant rats were infected with Streptococcus pneumoniae and treated with FLX or saline.
- Clinical outcomes, inflammatory markers in cerebrospinal fluid (CSF), and brain histomorphology were assessed at multiple time points.
- Apoptosis in the hippocampus and damage in cortical areas were quantified.
Main Results:
- FLX treatment significantly reduced hippocampal apoptosis compared to controls (9/19 vs 18/23, P=0.038).
- A trend towards reduced cortical damage was observed in FLX-treated rats, though not statistically significant.
- FLX did not significantly alter clinical or inflammatory parameters in the CSF.
Conclusions:
- Fluoxetine exhibits a significant neuroprotective effect on the hippocampus in experimental pneumococcal meningitis.
- FLX may serve as a potential adjuvant therapy to mitigate specific brain injuries associated with bacterial meningitis.
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