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Review
. 2015 Aug 3;7(3):175-87.
doi: 10.3390/pharmaceutics7030175.

Neurosurgical Techniques for Disruption of the Blood-Brain Barrier for Glioblastoma Treatment

Analiz Rodriguez  1 , Stephen B Tatter  2 , Waldemar Debinski  3
Affiliations
Review

Neurosurgical Techniques for Disruption of the Blood-Brain Barrier for Glioblastoma Treatment

Analiz Rodriguez et al. Pharmaceutics. .

Abstract

The blood-brain barrier remains a main hurdle to drug delivery to the brain. The prognosis of glioblastoma remains grim despite current multimodal medical management. We review neurosurgical technologies that disrupt the blood-brain barrier (BBB). We will review superselective intra-arterial mannitol infusion, focused ultrasound, laser interstitial thermotherapy, and non-thermal irreversible electroporation (NTIRE). These technologies can lead to transient BBB and blood-brain tumor barrier disruption and allow for the potential of more effective local drug delivery. Animal studies and preliminary clinical trials show promise for achieving this goal.

Keywords: blood–brain barrier; focused ultrasound; glioblastoma; intra-arterial drug delivery; laser interstitial thermotherapy; non-thermal irreversible electroporation.

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Figures

Figure 1
Figure 1
The blood–brain barrier is comprised of neurovascular units. Endothelial cells are connected by tight junctions and share a basement lamina with pericytes. Astrocytic end-feet are also at the basement lamina interface and these cells interact with neurons (This figure was developed using Servier Medical Art (http://www.servier.com/Powerpoint-image-bank) under a Creative Commons attribution 3.0 Unported License).
Figure 2
Figure 2
Schematic of mechanism of blood–brain barrier disruption by intra-arterial mannitol administration. The hyper-osmolar agent causes endothelial cell dehydration and subsequent shrinkage as well as tight junction disruption. This allows for increased permeability across the blood–brain barrier (This figure was developed using Servier Medical Art (http://www.servier.com/Powerpoint-image-bank) under a Creative Commons attribution 3.0 Unported License).
Figure 3
Figure 3
Schematic of blood–brain barrier disruption by focused ultrasound. Disruption of the blood–brain barrier can be induced when microbubbles apply mechanical forces on endothelial cells that lead to openings of the tight junctions (This figure was developed using Servier Medical Art (http://www.servier.com/Powerpoint-image-bank) under a Creative Commons attribution 3.0 Unported License).
Figure 4
Figure 4
Schematic of blood–brain barrier disruption by electroporation. A pulsed electric current causes direct defects into the cell membrane of the endothelial cells, resulting in increased permeability (This figure was developed using Servier Medical Art (http://www.servier.com/Powerpoint-image-bank) under a Creative Commons attribution 3.0 Unported License).
See this image and copyright information in PMC

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