Anti ICAM-1 (CD 54) monoclonal antibody reduces inflammatory changes in experimental bacterial meningitis
J R Weber1, K Angstwurm, W Bürger
1Department of Neurology, Universitätsklinikum Charité, Humboldt University Berlin, Germany.
Insights
Monoclonal antibodies targeting intracellular adhesion molecule 1 (ICAM-1) significantly reduced brain edema and intracranial pressure in a rat model of bacterial meningitis. This treatment also attenuated white blood cell invasion and improved cerebral blood flow.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Bacterial meningitis causes brain edema and increased intracranial pressure.
- The role of intracellular adhesion molecule 1 (ICAM-1) in early meningitis pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the therapeutic potential of ICAM-1 monoclonal antibodies (mAbs) in early bacterial meningitis.
- To assess the effects of ICAM-1 blockade on brain edema, intracranial pressure, cerebral blood flow, and white blood cell infiltration.
Main Methods:
- A rat model of bacterial meningitis was established using pneumococcal cell walls (PCW).
- Intravenous administration of ICAM-1 mAb (TM-8) was performed.
- Brain water content, intracranial pressure (ICP), regional cerebral blood flow (rCBF), and cerebrospinal fluid (CSF) white blood cell (WBC) counts were measured.
Main Results:
- ICAM-1 mAb treatment significantly inhibited increases in ICP and brain water content (P <0.05).
- Treatment with ICAM-1 mAb markedly attenuated increases in rCBF and WBC recruitment into the CSF (P <0.05).
Conclusions:
- The ICAM-1 pathway plays a critical role in the early stages of bacterial meningitis.
- Targeting ICAM-1 with monoclonal antibodies shows promise for treating early bacterial meningitis by reducing key pathological markers.
Abstract:
We investigated whether monoclonal antibodies directed against intracellular adhesion molecule 1 (ICAM-1 mAb) inhibit brain edema, increase of intracranial pressure (ICP), regional cerebral blood flow (rCBF) and recruitment of white blood cells (WBC) into the cerebrospinal fluid (CSF) in the rat model of the early phase of bacterial meningitis. Brain edema was assessed by brain water content determinations. rCBF measured by laser Doppler flowmetry and ICP were recorded continuously for 6 h after intracisternal challenge. Meningitis was induced with pneumococcal cell walls (PCW). Increase of ICP and brain water content were significantly inhibited (P <0.05) by intravenous treatment with ICAM-1 mAb (TM-8, 1 mg/kg). Furthermore, ICAM-1 mAb treatment profoundly attenuated (P <0.05) rCBF increase and WBC invasion into the CSF. These results suggest that the ICAM-1 pathway is critically involved in the early phase of bacterial meningitis.
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