Related Experiment Videos
The polysaccharide fucoidin inhibits the antibiotic-induced inflammatory cascade in experimental pneumococcal
C Granert1, J Raud, L Lindquist
1Department of Infectious Diseases, Huddinge Hospital, Sweden.
Abstract:
There is evidence that the treatment of bacterial meningitis with antibiotics liberates harmful bacterial products in the subarachnoid space (SAS). This enhances meningeal inflammation and in particular the recruitment of leukocytes into the cerebrospinal fluid (CSF), which has been shown to be more harmful than beneficial in this disease. In this study, we used a rabbit meningitis model based on intracisternal injection of live Streptococcus pneumoniae. Ampicillin (40 mg/kg of body weight given intravenously [i.v.] 16 h after induction of meningitis) caused a fivefold increase in CSF leukocytes over a 4-h period. Inhibition of leukocyte rolling by treatment with the polysaccharide fucoidin (10 mg/kg, i.v.) prevented the enhanced leukocyte extravasation into the SAS and attenuated the leakage of plasma proteins over the blood-brain barrier. These results suggest that certain polysaccharides that block leukocyte rolling have the potential to reduce leukocyte-dependent central nervous system damage in bacterial meningitis.
Insights
Antibiotic treatment for bacterial meningitis can worsen inflammation by increasing white blood cell (leukocyte) entry into the brain. Polysaccharides that block leukocyte rolling may reduce this central nervous system damage.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Antibiotic treatment for bacterial meningitis can paradoxically increase harmful inflammation.
- Bacterial products released by antibiotics enhance leukocyte recruitment into the cerebrospinal fluid (CSF).
- This leukocyte influx into the subarachnoid space (SAS) contributes to central nervous system (CNS) damage.
Purpose of the Study:
- To investigate the therapeutic potential of blocking leukocyte recruitment in bacterial meningitis.
- To evaluate the effect of fucoidin, a leukocyte rolling inhibitor, in a rabbit meningitis model.
Main Methods:
- A rabbit model of bacterial meningitis was established using Streptococcus pneumoniae.
- Ampicillin was administered intravenously to induce increased CSF leukocytes.
- Fucoidin was administered intravenously to inhibit leukocyte rolling and assess its effects on leukocyte and plasma protein leakage.
Main Results:
- Ampicillin treatment significantly increased CSF leukocytes (fivefold) within 4 hours.
- Fucoidin treatment prevented the ampicillin-induced increase in leukocyte extravasation into the SAS.
- Fucoidin also attenuated plasma protein leakage across the blood-brain barrier.
Conclusions:
- Leukocyte rolling is a critical mechanism for CNS damage in bacterial meningitis.
- Polysaccharides like fucoidin that inhibit leukocyte rolling show promise in reducing meningitis-associated neurological injury.
- Targeting leukocyte recruitment offers a potential therapeutic strategy to mitigate CNS damage in bacterial meningitis.