{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T21:10:43Z","timestamp":1772226643755,"version":"3.50.1"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1159120"],"award-info":[{"award-number":["1159120"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Neurovascular coupling (NVC) leads to an increase in local cerebral blood flow and oxygenation in response to increased neural activity and metabolic demand. Impaired or immature NVC reported in the preterm brain, potentially reduces cerebral oxygenation following increased neural activity, predisposing to cerebral tissue hypoxia. Endogenous nitric oxide (NO) is a potent vasodilator and a major mediator of NVC and the cerebral haemodynamic response. NO modulators, such as inhaled nitric oxide (iNO) and sildenafil, induce vasodilation and are used clinically to treat pulmonary hypertension in preterm neonates. However, their impact on NVC in the preterm brain are unknown. We aimed to characterise the cerebral functional haemodynamic response in the preterm brain exposed to NO modulators. We hypothesized that iNO and sildenafil in clinical dosages would increase the baseline cerebral perfusion and the cerebral haemodynamic response to neural activation.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Preterm lambs (126\u20137\u00a0days\u2019 gestation) were delivered and mechanically ventilated. The cerebral functional haemodynamic response was measured using near infrared spectroscopy as changes in cerebral oxy- and deoxyhaemoglobin (\u0394oxyHb, \u0394deoxyHb), following left median nerve stimulations of 1.8, 4.8, and 7.8\u00a0s durations in control preterm lambs (<jats:italic>n<\/jats:italic> = 11), and following 4.8 and 7.8\u00a0s stimulations in preterm lambs receiving either sildenafil citrate (<jats:italic>n<\/jats:italic> = 6, 1.33\u00a0mcg\/kg\/hr) or iNO (<jats:italic>n<\/jats:italic> = 8, 20\u00a0ppm).<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Following 1.8, 4.8, and 7.8\u00a0s stimulations, \u2206oxyHb in the contralateral cortex increased (positive functional response) in 7\/11 (64%), 7\/11 (64%), and 4\/11 (36%) control lambs respectively (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). Remaining lambs showed decreased \u0394oxyHb (negative functional response). Following 4.8\u00a0s stimulations, more lambs receiving sildenafil or iNO (83% and 100% respectively) showed positive functional response compared to the controls (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). No significant difference between the three groups was observed at 7.8\u00a0s stimulations.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> In the preterm brain, prolonged somatosensory stimulations increased the incidence of negative functional responses with decreased cerebral oxygenation, suggesting that cerebral oxygen delivery may not match the oxygen demand. Sildenafil and iNO increased the incidence of positive functional responses, potentially enhancing NVC, and cerebral oxygenation.<\/jats:p>","DOI":"10.3389\/fphys.2023.1101647","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T05:32:50Z","timestamp":1674624770000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Cerebral haemodynamic response to somatosensory stimulation in preterm lambs is enhanced following sildenafil and inhaled nitric oxide administration"],"prefix":"10.3389","volume":"14","author":[{"given":"Ishmael Miguel","family":"Inocencio","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Navneet","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nhi T.","family":"Tran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flora Y.","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1758-5996-4-2","article-title":"Autonomic cerebral vascular response to sildenafil in diabetic patient","volume":"4","author":"Al-Amran","year":"2012","journal-title":"Diabetol. 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