{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:03:42Z","timestamp":1789495422608,"version":"build-2803163510"},"reference-count":59,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,19]],"date-time":"2021-06-19T00:00:00Z","timestamp":1624060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","award":["18\/183"],"award-info":[{"award-number":["18\/183"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","award":["20\/101 and 17\/601"],"award-info":[{"award-number":["20\/101 and 17\/601"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001515","name":"Cure Kids","doi-asserted-by":"publisher","award":["3581"],"award-info":[{"award-number":["3581"]}],"id":[{"id":"10.13039\/501100001515","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009477","name":"Lottery Health Research","doi-asserted-by":"publisher","award":["R-LHR-2017-48693"],"award-info":[{"award-number":["R-LHR-2017-48693"]}],"id":[{"id":"10.13039\/501100009477","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001518","name":"Maurice and Phyllis Paykel Trust","doi-asserted-by":"publisher","award":["M.F."],"award-info":[{"award-number":["M.F."]}],"id":[{"id":"10.13039\/501100001518","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gravida: National Centre for Growth and Development","award":["STF-13-22"],"award-info":[{"award-number":["STF-13-22"]}]},{"name":"Barbara Basham Doctoral Scholarship","award":["1216004"],"award-info":[{"award-number":["1216004"]}]},{"DOI":"10.13039\/501100001511","name":"Auckland Medical Research Foundation","doi-asserted-by":"publisher","award":["1117009"],"award-info":[{"award-number":["1117009"]}],"id":[{"id":"10.13039\/501100001511","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Toll-like receptor (TLR) agonists are key immunomodulatory factors that can markedly ameliorate or exacerbate hypoxic\u2013ischemic brain injury. We recently demonstrated that central infusion of the TLR7 agonist Gardiquimod (GDQ) following asphyxia was highly neuroprotective after 3 days but not 7 days of recovery. We hypothesize that this apparent transient neuroprotection is associated with modulation of seizure-genic processes and hemodynamic control. Methods: Fetuses received sham asphyxia or asphyxia induced by umbilical cord occlusion (20.9 \u00b1 0.5 min) and were monitored continuously for 7 days. GDQ 3.34 mg or vehicle were infused intracerebroventricularly from 1 to 4 h after asphyxia. Results: GDQ infusion was associated with sustained moderate hypertension that resolved after 72 h recovery. Electrophysiologically, GDQ infusion was associated with reduced number and burden of postasphyxial seizures in the first 18 h of recovery (p &lt; 0.05). Subsequently, GDQ was associated with induction of slow rhythmic epileptiform discharges (EDs) from 72 to 96 h of recovery (p &lt; 0.05 vs asphyxia + vehicle). The total burden of EDs was associated with reduced numbers of neurons in the caudate nucleus (r2 = 0.61, p &lt; 0.05) and CA1\/2 hippocampal region (r2 = 0.66, p &lt; 0.05). Conclusion: These data demonstrate that TLR7 activation by GDQ modulated blood pressure and suppressed seizures in the early phase of postasphyxial recovery, with subsequent prolonged induction of epileptiform activity. Speculatively, this may reflect delayed loss of early protection or contribute to differential neuronal survival in subcortical regions.<\/jats:p>","DOI":"10.3390\/ijms22126593","type":"journal-article","created":{"date-parts":[[2021,6,20]],"date-time":"2021-06-20T22:00:02Z","timestamp":1624226402000},"page":"6593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Induction of Tertiary Phase Epileptiform Discharges after Postasphyxial Infusion of a Toll-Like Receptor 7 Agonist in Preterm Fetal Sheep"],"prefix":"10.3390","volume":"22","author":[{"given":"Kenta H.T.","family":"Cho","sequence":"first","affiliation":[{"name":"The Department of Physiology, The University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mhoyra","family":"Fraser","sequence":"additional","affiliation":[{"name":"The Department of Physiology, The University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Xu","sequence":"additional","affiliation":[{"name":"Shenzhen Bay Laboratory, Shenzhen 518118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1377-0878","authenticated-orcid":false,"given":"Justin M.","family":"Dean","sequence":"additional","affiliation":[{"name":"The Department of Physiology, The University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0656-7035","authenticated-orcid":false,"given":"Alistair J.","family":"Gunn","sequence":"additional","affiliation":[{"name":"The Department of Physiology, The University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bennet","sequence":"additional","affiliation":[{"name":"The Department of Physiology, The University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103.e1","DOI":"10.1016\/j.ajog.2016.01.004","article-title":"Preterm neonatal morbidity and mortality by gestational age: A contemporary cohort","volume":"215","author":"Manuck","year":"2016","journal-title":"Am. 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