Title |
Real-time monitoring of human blood-brain barrier disruption
|
---|---|
Published in |
PLOS ONE, March 2017
|
DOI | 10.1371/journal.pone.0174072 |
Pubmed ID | |
Authors |
Vesa Kiviniemi, Vesa Korhonen, Jukka Kortelainen, Seppo Rytky, Tuija Keinänen, Timo Tuovinen, Matti Isokangas, Eila Sonkajärvi, Topi Siniluoto, Juha Nikkinen, Seppo Alahuhta, Osmo Tervonen, Taina Turpeenniemi-Hujanen, Teemu Myllylä, Outi Kuittinen, Juha Voipio |
Abstract |
Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography (DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 μV followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for blood-brain barrier disruption augmented drug delivery. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Germany | 2 | 33% |
Unknown | 4 | 67% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 6 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | <1% |
Unknown | 103 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 23 | 22% |
Student > Master | 13 | 13% |
Researcher | 12 | 12% |
Student > Bachelor | 11 | 11% |
Student > Doctoral Student | 9 | 9% |
Other | 17 | 16% |
Unknown | 19 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 19 | 18% |
Neuroscience | 15 | 14% |
Biochemistry, Genetics and Molecular Biology | 8 | 8% |
Engineering | 8 | 8% |
Psychology | 4 | 4% |
Other | 21 | 20% |
Unknown | 29 | 28% |