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The impact of CAS on cerebral blood flow (CBF) within the ipsilateral hemisphere relies on the adaptive capabilities of the cerebral microcirculation. In this study, we aimed to test the hypothesis that the impaired availability of nitric oxide (NO) compromises CBF homeostasis after unilateral carotid artery occlusion (CAO). To investigate this, three mouse models exhibiting compromised production of NO were tested: NOS1 knockout, NOS1\/3 double knockout, and mice treated with the NO synthesis inhibitor L-NAME. Regional CBF changes following CAO were evaluated using laser-speckle contrast imaging (LSCI). Our findings demonstrated that NOS1 knockout, NOS1\/3 double knockout, and L-NAME-treated mice exhibited impaired CBF adaptation to CAO. Furthermore, genetic deficiency of one or two NO synthase isoforms increased the tortuosity of pial collaterals connecting the frontoparietal and temporal regions. In conclusion, our study highlights the significant contribution of NO production to the functional adaptation of cerebrocortical microcirculation to unilateral CAO. We propose that impaired bioavailability of NO contributes to the impaired CBF homeostasis by altering inter- and intrahemispheric blood flow redistribution after unilateral disruption of carotid artery flow.<\/jats:p>","DOI":"10.3390\/ijms25020697","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T05:12:17Z","timestamp":1704431537000},"page":"697","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["NO Deficiency Compromises Inter- and Intrahemispheric Blood Flow Adaptation to Unilateral Carotid Artery Occlusion"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8320-2166","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"Hricis\u00e1k","sequence":"first","affiliation":[{"name":"Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary"},{"name":"HUN-REN-SU Cerebrovascular and Neurocognitive Diseases 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