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Related Experiment Videos

Blood-brain barrier disruption using mannitol: time course and electron microscopy studies.

W C Cosolo1, P Martinello, W J Louis

  • 1Department of Clinical Pharmacology and Therapeutics, Austin Hospital, Heidelberg, Australia.

The American Journal of Physiology
|February 1, 1989
PubMed
Summary

Optimizing mannitol infusion for blood-brain barrier disruption enhances intracerebral methotrexate delivery in rats. The ideal rate of 0.25 ml.s-1.kg-1 for 20 seconds maximizes drug levels without neurological side effects.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Biomedical Engineering

Background:

  • The blood-brain barrier (BBB) restricts drug delivery to the brain.
  • Mannitol-induced BBB disruption can increase intracerebral drug concentrations.
  • Previous studies indicate potential for BBB disruption to enhance chemotherapy for brain tumors.

Purpose of the Study:

  • To determine optimal mannitol infusion parameters for BBB disruption.
  • To achieve BBB opening without causing neurological damage.
  • To establish conditions for enhanced intracerebral drug delivery, specifically methotrexate.

Main Methods:

  • Adult Sprague-Dawley rats were used.
  • Mannitol was infused via the internal carotid artery at varying rates (0.25-0.5 ml.s-1.kg-1).

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  • Methotrexate and Evans blue served as markers for BBB disruption; neurological assessments were performed.

    • Main Results:

    • The optimal mannitol infusion rate was 0.25 ml.s-1.kg-1 for 20 seconds.
    • BBB opening peaked around 5 minutes and rapidly reversed.
    • Intracerebral methotrexate levels were 4-5 times higher on the infused side.
    • No consistent neurological sequelae or microstructural changes were observed via microscopy.

    Conclusions:

    • The identified mannitol infusion parameters enable controlled BBB disruption.
    • This method effectively enhances intracerebral methotrexate delivery.
    • The model is suitable for investigating BBB disruption strategies for treating brain tumors.
    • Maximal methotrexate levels are achieved when infused before or within 5 minutes of mannitol administration.