Real-time monitoring of human blood-brain barrier disruption

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Kiviniemi , V , Korhonen , V , Kortelainen , J , Rytky , S , Keinanen , T , Tuovinen , T , Isokangas , M , Sonkajarvi , E , Siniluoto , T , Nikkinen , J , Alahuhta , S , Tervonen , O , Turpeenniemi-Hujanen , T , Myllyla , T , Kuittinen , O & Voipio , J 2017 , ' Real-time monitoring of human blood-brain barrier disruption ' , PLoS One , vol. 12 , no. 3 , 0174072 .

Title: Real-time monitoring of human blood-brain barrier disruption
Author: Kiviniemi, Vesa; Korhonen, Vesa; Kortelainen, Jukka; Rytky, Seppo; Keinanen, Tuija; Tuovinen, Timo; Isokangas, Matti; Sonkajarvi, Eila; Siniluoto, Topi; Nikkinen, Juha; Alahuhta, Seppo; Tervonen, Osmo; Turpeenniemi-Hujanen, Taina; Myllyla, Teemu; Kuittinen, Outi; Voipio, Juha
Contributor organization: Biosciences
Juha Voipio / Principal Investigator
Laboratory of Neurobiology
Date: 2017-03-20
Language: eng
Number of pages: 16
Belongs to series: PLoS One
ISSN: 1932-6203
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 mu V 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 bloodbrain barrier disruption augmented drug delivery.
3112 Neurosciences
3122 Cancers
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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