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

Cosolo, W; Martinello, Paul; Louis, William J.; Christophidis, N.

doi:10.1152/ajpregu.1989.256.2.r443

Cited by 63 publications

(68 citation statements)

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“…These strategies rely on drugs diffusion which is very slow in the cerebral parenchyma and can cause infections and cerebral edemas [240], not to mention the discomfort they pose to the patient. Nonsurgical strategies such as the modification of drugs to produce lipophilic analogs and prodrugs [241], and the generation of a transient disruption of the BBB through the intracarotid administration of agents such as mannitol, leukotrienes, and vasoactive peptides have also been investigated [242,243].…”

Section: Brain Targetingmentioning

confidence: 99%

Antibody-Conjugated Nanoparticles for Therapeutic Applications

Cardoso

Peça²,

Roque³

2012

CMC

109

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Abstract:A great challenge to clinical development is the delivery of chemotherapeutic agents, known to cause severe toxic effects, directly to diseased sites which increase the therapeutic index whilst minimizing off-target side effects. Antibody-conjugated nanoparticles offer great opportunities to overcome these limitations in therapeutics. They combine the advantages given by the nanoparticles with the ability to bind to their target with high affinity and improve cell penetration given by the antibodies. This specialized vehicle, that can encapsulate several chemotherapeutic agents, can be engineered to possess the desirable properties, allowing overcoming the successive physiological conditions and to cross biological barriers and reach a specific tissue or cell. Moreover, antibody-conjugated nanoparticles have shown the ability to be internalized through receptor-mediated endocytosis and accumulate in cells without being recognized by the P-glycoprotein, one of the main mediators of multi-drug resistance, resulting in an increase in the intracellular concentration of drugs. Also, progress in antibody engineering has allowed the manipulation of the basic antibody structure for raising and tailoring specificity and functionality. This review explores recent developments on active drug targeting by nanoparticles functionalized with monoclonal antibodies (polymeric micelles, liposomes and polymeric nanoparticles) and summarizes the opportunities of these targeting strategies in the therapy of serious diseases (cancer, inflammatory diseases, infectious diseases, and thrombosis).

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Section: Brain Targetingmentioning

confidence: 99%

Antibody-Conjugated Nanoparticles for Therapeutic Applications

Cardoso

Peça²,

Roque³

2012

CMC

109

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“…Several factors can negatively impact the effectiveness of the BBBD; hemodynamic variables, anesthetic agent and rate of infusion of hypertonic solutions are but a few examples (43,46). As a consequence, even repeated procedures in the same individual or animal can lead to highly variable BBB disruptions.…”

Section: Albuminmentioning

confidence: 99%

Recent Advances in Blood–Brain Barrier Disruption as a CNS Delivery Strategy

Bellavance

Blanchette

Fortin

2008

AAPS J

162

113

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Abstract. The blood-brain barrier (BBB) is a complex functional barrier composed of endothelial cells, pericytes, astrocytic endfeets and neuronal cells. This highly organized complex express a selective permeability for molecules that bear, amongst other parameters, adequate molecular weight and sufficient liposolubility. Unfortunately, very few therapeutic agents currently available do cross the BBB and enters the CNS. As the BBB limitation is more and more acknowledged, many innovative surgical and pharmacological strategies have been developed to circumvent it. This review focuses particularly on the osmotic opening of the BBB, a well-documented approach intended to breach the BBB. Since its inception by Rapoport in 1972, pre-clinical studies have provided important information on the extent of BBB permeation. Thanks to Neuwelt and colleagues, the osmotic opening of the BBB made its way to the clinic. However, many questions remain as to the detailed physiology of the procedure, and its best application to the clinic. Using different tools, amongst which MRI as a real-time in vivo characterization of the BBB permeability and CNS delivery, we attempt to better define the osmotic BBB permeabilization physiology. These ongoing studies are described, and data related to spatial and temporal distribution of a molecule after osmotic BBB breaching, as well as the window of BBB permeabilization, are discussed. We also summarize recent clinical series highlighting promising results in the application of this procedure to maximize delivery of chemotherapy in the treatment of brain tumor patients.KEY WORDS: blood-brain barrier, blood-brain barrier disruption, brain tumors, CNS delivery; MRI.

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“…Mannitol was used as an hyperosmolar agent because of its low toxicity and the well-documented time course of its action (Cosolo et al, 1989). As a marker for increased permeability of the blood-brain barrier we chose Evans Blue which can be detected in small quantities by fluorescence microscopy techniques.…”

Section: Introductionmentioning

confidence: 99%

Inhibition by sumatriptan of central trigeminal neurones only after blood‐brain barrier disruption

Kaube

Hoskin

Goadsby

1993

British J Pharmacology

214

105

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1 The 5-hydroxytryptamine (5-HT,)-like agonist, sumatriptan, is highly efficient in the relief of migraine headache and its accompanying symptoms. 2 Experimental evidence has indicated that its site of action may be on the cranial vessels or on the trigeminal innervation of the cranium, or both, since sumatriptan does not pass the blood-brain barrier easily under normal circumstances. It is, however, not clear whether the blood-brain barrier is normal or abnormal during a migraine attack. 3 In this study, single unit activity and trigeminal somatosensory evoked potentials in central trigeminal neurones were monitored during electrical stimulation of the superior sagittal sinus. 4 Intravenous administration of sumatriptan (100 ig kg-') did not alter trigeminal evoked activity unless the permeability of the blood-brain barrier had been increased by infusion of an hyperosmolar mannitol solution. After blood-brain barrier disruption, sumatriptan decreased the peak-to-peak amplitude of evoked potentials by 40 ± 6% and the probability of firing of single units by 30 ± 9%. Mannitol infusions alone in control animals caused no changes in evoked potentials or single unit activity. 5 The data suggest that in normal circumstances sumatriptan does not have sufficient access to trigeminal neurones to alter their function.

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

Cited by 63 publications

References 0 publications

Antibody-Conjugated Nanoparticles for Therapeutic Applications

Antibody-Conjugated Nanoparticles for Therapeutic Applications

Recent Advances in Blood–Brain Barrier Disruption as a CNS Delivery Strategy

Inhibition by sumatriptan of central trigeminal neurones only after blood‐brain barrier disruption

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