Intracerebral Dialysis and the Blood‐Brain Barrier

Westergren, Irena; Nyström, Britta; Hamberger, Anders; Johansson, Barbro

doi:10.1046/j.1471-4159.1995.64010229.x

Cited by 77 publications

(27 citation statements)

References 9 publications

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“…As shown in Figures 4a through 4d, albumin failed to cross the intact BBB (Figures 4e through 4h). In contrast, after mechanically induced BBB breakdown, 20 extravasation of albumin in the brain parenchyma was observed as a positive control (Figures 4i through 4l). In addition, Figures 4m and 4n, which include GFAP immunostaining, show that the tPA that crosses the intact BBB diffuses at a distance up to that of the astrocytic end feet.…”

Section: Benchenane Et Al Tpa An Interface Between Brain and Blood 2mentioning

confidence: 97%

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Tissue-Type Plasminogen Activator Crosses the Intact Blood-Brain Barrier by Low-Density Lipoprotein Receptor–Related Protein-Mediated Transcytosis

et al. 2005

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Background-Accumulating evidence demonstrates a critical involvement of tissue-type plasminogen activator (tPA) in pathological and physiological brain conditions. Determining whether and how vascular tPA can cross the blood-brain barrier (BBB) to enter the brain is thus important, not only during stroke but also in physiological conditions. Methods and Results-In the present work, we provide evidence in vivo that intravenous injection of tPA increases NMDA-induced striatal lesion in the absence of BBB leakage. Accordingly, we show that tPA crosses the BBB both after excitotoxic lesion and in control conditions. Indeed, vascular injected tPA can be detected within the brain parenchyma and in the cerebrospinal fluid. By using an in vitro model of BBB, we have confirmed that tPA can cross the intact BBB. Its passage was blocked at 4°C, was saturable, and was independent of its proteolytic activity. We have shown that tPA crosses the BBB by transcytosis, mediated by a member of the LDL receptor-related protein family. Conclusions-We demonstrate that blood-derived tPA can reach the brain parenchyma without alteration of the BBB. The molecular mechanism of the passage of tPA from blood to brain described here could represent an interesting target to improve thrombolysis in stroke (Circulation. 2005;111:2241-2249.)

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Section: Benchenane Et Al Tpa An Interface Between Brain and Blood 2mentioning

confidence: 97%

“…Mechanically induced BBB breakdown for positive control was performed as described by Westergren and colleagues. 20 …”

Section: Fitc Injection and Confocal Microscopy For Determination Of mentioning

confidence: 99%

Tissue-Type Plasminogen Activator Crosses the Intact Blood-Brain Barrier by Low-Density Lipoprotein Receptor–Related Protein-Mediated Transcytosis

et al. 2005

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“…The significant volume of tissue damage surrounding the microdialysis probe (Clapp-Lilly et al, 1999) could dramatically increase the distance between the probe tip and undamaged, transporter-expressing astrocytic membrane. We speculate that this transporter-free space surrounding the microdialysis probe, along with damage to the blood-brain barrier (Westergren et al, 1995), allows for buildup of extracellular glutamate and results in an artificially high ambient glutamate estimate. Our data support this speculation by showing that acutely blocking transport with TBOA increased the ambient glutamate concentration, even in conditions in which neuronal activity was blocked.…”

Section: Glutamate Transport Is Highly Efficientmentioning

confidence: 99%

Extracellular Glutamate Concentration in Hippocampal Slice

2007

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Synaptic glutamate transients resulting from vesicular exocytosis are superimposed on a low baseline concentration of glutamate in the extracellular space. Reported values of baseline glutamate concentrations range up to 4 M. If glutamate were present tonically at low micromolar concentrations, many receptors, especially the high-affinity NMDA receptors (NMDARs), would be activated or desensitized, altering neuronal excitability. Using NMDARs expressed by CA1 pyramidal cells in acute hippocampal slices to monitor extracellular glutamate, we find that its baseline concentration is much lower, near 25 nM. In addition, superfusion of low micromolar concentrations of glutamate had no effect on neurons, indicating that glutamate transport prevents access to receptors within the slice. However, equipotent concentrations of NMDA, a nontransported agonist, depolarized neurons dramatically. We suggest that ambient concentrations of glutamate in vivo are also in the nanomolar range and are too low to cause significant receptor activation.

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“…Microdialysis, characterized as a minimal invasive technique, causes local tissue damage and perturbation of the BBB function. Several studies have reported relatively (within hours) fast restoration of the BBB following the insertion of the microdialysis probe (Benveniste et al, 1989;Dykstra et al, 1992;de Lange et al, 1995), whereas other reports call for a caution when using microdialysis to study normal BBB function (Westergren et al, 1995;Morgan et al, 1996;Groothuis et al, 1998). The latter reports suggest that microdialysis may overestimate the rate of drug transfer Fig.…”

Section: Resultsmentioning

confidence: 99%