Abstract | BACKGROUND: METHODS: A well-established infant rat model of PM was used where live Streptococcus pneumoniae were injected intracisternally and antibiotic treatment with ceftriaxone was initiated 18 h post infection (hpi). Treatment with RS-130830 (75 mg/kg bis in die (bid) i.p., n = 40) was started at 3 hpi while control littermates received the vehicle (succinylated gelatine, n = 42). RESULTS: Cortical necrosis was significantly attenuated in animals treated with RS-130830, while the extent of hippocampal apoptosis was not influenced. At 18 hpi, concentrations of interleukin (IL)-1β and IL-10 were significantly lower in the cerebrospinal fluid of treated animals compared to controls. RS-130830 significantly reduced weight loss and leukocyte counts in the cerebrospinal fluid of survivors of PM. CONCLUSION: This study identifies MMP inhibition, specifically with RS-130830, as an efficient strategy to attenuate disease severity and cortical brain injury in PM.
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Authors | Fabian D Liechti, Fabian Bächtold, Denis Grandgirard, David Leppert, Stephen L Leib |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 12
Pg. 43
(Mar 04 2015)
ISSN: 1742-2094 [Electronic] England |
PMID | 25890041
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cytokines
- Enzyme Inhibitors
- Hydroxamic Acids
- RS-130830
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Topics |
- Animals
- Animals, Newborn
- Brain Injuries
(drug therapy, etiology, microbiology)
- Cytokines
(metabolism)
- Disease Models, Animal
- Enzyme Inhibitors
(therapeutic use)
- Hydroxamic Acids
(therapeutic use)
- Leukocytes
(pathology)
- Meningitis, Pneumococcal
(complications)
- Rats
- Rats, Wistar
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