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Updated: Jun 3, 2026
Non-Invasive Model of Neuropathogenic Escherichia coli Infection in the Neonatal Rat
Published on: October 29, 2014
Ciprofloxacin prevents myelination delay in neonatal rats subjected to E. coli sepsis
Gauthier Loron1, Paul Olivier, Hélène See
1Institut National de la Santé et de la Recherche Médicale AVENIR, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, France.
Insights
Ciprofloxacin (CIP) reduces white matter inflammation and damage in neonatal rat sepsis models. This neuroprotective effect, independent of antibacterial action, involves modulating inducible nitric oxide synthase (iNOS) expression.
Area of Science:
- Neonatal Neurology
- Neuroinflammation
- White Matter Diseases
Background:
- Perinatal infections trigger systemic inflammation, a key cause of white matter disease (WMD) in developing brains.
- Antibiotics are used, but neuroprotective strategies targeting inflammation are needed.
- Fluoroquinolones like ciprofloxacin (CIP) possess anti-inflammatory properties.
Purpose of the Study:
- To investigate the neuroprotective potential of CIP in neonatal sepsis-induced WMD.
- To compare CIP's efficacy against cefotaxime (CTX) in modulating white matter inflammation.
- To determine if CIP's effects are independent of its antibacterial activity.
Main Methods:
- An Escherichia coli sepsis model was established in 5-day-old rat pups (P5).
- CIP and CTX were administered to compare their effects on sepsis-induced white matter inflammation and damage.
- A noninfectious white matter inflammation model was used to assess CIP's anti-inflammatory effects.
Main Results:
- CIP significantly reduced microglial activation and inducible nitric oxide synthase (iNOS) expression compared to CTX.
- CIP prevented sepsis-induced myelination delay and promoted oligodendroglial survival and maturation.
- CIP normalized altered transcription of guidance molecules semaphorin 3A and 3F.
Conclusions:
- CIP demonstrates significant neuroprotective effects in a neonatal sepsis-induced WMD model.
- These benefits appear independent of antibacterial activity, likely mediated by iNOS modulation.
- CIP offers a potential therapeutic strategy for WMD in neonatal sepsis.
Objective:
Perinatal infections and the systemic inflammatory response to them are critical contributors to white matter disease (WMD) in the developing brain despite the use of highly active antibiotics. Fluoroquinolones including ciprofloxacin (CIP) have intrinsic anti-inflammatory effects. We hypothesized that CIP, in addition to its antibacterial activity, could exert a neuroprotective effect by modulating white matter inflammation in response to sepsis.
Methods:
We adapted an Escherichia coli sepsis model to 5-day-old rat pups (P5), to induce white matter inflammation without bacterial meningitis. We then compared the ability of CIP to modulate inflammatory-induced brain damage compared with cefotaxime (CTX) (treatment of reference).
Results:
Compared with CTX, CIP was associated with reduced microglial activation and inducible nitric oxide synthase (iNOS) expression in the developing white matter in rat pups subjected to E. coli sepsis. In addition to reducing microglial activation, CIP was able to prevent myelination delay induced by E. coli sepsis and to promote oligodendroglial survival and maturation. We found that E. coli sepsis altered the transcription of the guidance molecules semaphorin 3A and 3F; CIP treatment was capable of reducing semaphorin 3A and 3F transcription levels to those seen in uninfected controls. Finally, in a noninfectious white matter inflammation model, CIP was associated with significantly reduced microglial activation and prevented WMD when compared to CTX.
Interpretation:
These data strongly suggest that CIP exerts a beneficial effect in a model of E. coli sepsis-induced WMD in rat pups that is independent of its antibacterial activity but likely related to iNOS expression modulation.
