TLR7 agonist modulation of postasphyxial neurophysiological and cardiovascular adaptations in preterm fetal sheep.

Show simple item record Cho, KH en Fraser, Mhoyra en Wassink, Guido en Dhillon, SK en Davidson, Joanne en Dean, Justin en Gunn, Alistair en Bennet, Laura en 2020-07-10T04:20:45Z en 2020-02 en
dc.identifier.issn 0363-6119 en
dc.identifier.uri en
dc.description.abstract Activation of Toll-like receptors (TLRs) after hypoxic-ischemic brain injury can exacerbate injury but also alleviate cell loss, as recently demonstrated with the TLR7 agonist Gardiquimod (GDQ). However, TLR agonists also modulate vascular function and neuronal excitability. Thus, we examined the effects of TLR7 activation with GDQ on cardiovascular function and seizures after asphyxia in preterm fetal sheep at 0.7 gestation (104 days, term ∼147 days). Fetuses received sham asphyxia or asphyxia induced by umbilical cord occlusion for 25 min or asphyxia followed by a continuous intracerebroventricular infusion of 3.34 mg of GDQ from 1 to 4 h after asphyxia. Fetuses were monitored continuously for 72 h postasphyxia. GDQ treatment was associated with sustained, moderate hypertension for 72 h (P < 0.05), with a transient increase in heart rate. Electroencephalographic (EEG) power was suppressed for the entire postasphyxial period in both groups, whereas EEG spectral edge transiently increased during the GDQ infusion compared with asphyxia alone (P < 0.05), with higher β- and lower δ-EEG frequencies (P < 0.05). This increase in EEG frequency was not related to epileptiform activity. After the GDQ infusion, there was earlier onset of high-amplitude stereotypic evolving seizures, with increased numbers of seizures and seizure burden (P < 0.05). Hemodynamic function and seizure activity are important indices of preterm wellbeing. These data highlight the importance of physiological monitoring during preclinical testing of potential neuroprotective strategies. en
dc.format.medium Print-Electronic en
dc.language eng en
dc.relation.ispartofseries American journal of physiology. Regulatory, integrative and comparative physiology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.title TLR7 agonist modulation of postasphyxial neurophysiological and cardiovascular adaptations in preterm fetal sheep. en
dc.type Journal Article en
dc.identifier.doi 10.1152/ajpregu.00295.2019 en
pubs.issue 2 en
pubs.begin-page R369 en
pubs.volume 318 en
dc.rights.holder Copyright: The author en
pubs.end-page R378 en
pubs.publication-status Published en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 793608 en Medical and Health Sciences en Medical Sciences en Physiology Division en
dc.identifier.eissn 1522-1490 en
pubs.record-created-at-source-date 2020-06-11 en
pubs.dimensions-id 31913689 en

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