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Alterations in the neurovascular coupling system have been shown to lead to dysregulated energy supply to brain regions in several neurological diseases, including HD, which could potentially trigger the process of neurodegeneration. In particular, it has been observed in cross-sectional human HD studies that vascular alterations are associated to impaired cerebral blood flow (CBF). To assess whether whole-brain changes in CBF are present and follow a pattern of progression, we investigated both resting-state brain perfusion and vascular reactivity longitudinally in the zQ175DN mouse model of HD.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Using pseudo-continuous arterial spin labelling (pCASL) MRI in the zQ175DN model of HD and age-matched wild-type\u00a0(WT) mice, we assessed whole-brain, resting-state perfusion at 3, 6 and 9 and 13\u00a0months of age, and assessed hypercapnia-induced cerebrovascular reactivity (CVR), at 4.5, 6, 9 and 15\u00a0months of age.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found increased perfusion in cortical regions of zQ175DN HET mice at 3\u00a0months of age, and a reduction of this anomaly at 6 and 9\u00a0months, ages at which behavioural deficits have been reported. On the other hand, under hypercapnia, CBF was reduced in zQ175DN HET mice as compared to the WT: for multiple brain regions at 6\u00a0months of age, for only somatosensory and retrosplenial cortices at 9\u00a0months of age, and brain-wide by 15\u00a0months. CVR impairments in cortical regions, the thalamus and globus pallidus were observed in zQ175DN HET mice at 9\u00a0months, with whole brain reactivity diminished at 15\u00a0months of age. Interestingly, blood vessel density was increased in the motor cortex at 3\u00a0months, while average vessel length was reduced in the lateral portion of the caudate putamen at 6\u00a0months of age.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our findings reveal early cortical resting-state hyperperfusion and impaired CVR at ages that present motor anomalies in this HD model, suggesting that further characterization of brain perfusion alterations in animal models is warranted as a potential therapeutic target in HD.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12929-024-01028-3","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T15:19:33Z","timestamp":1713280773000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Longitudinal alterations in brain perfusion and vascular reactivity in the zQ175DN mouse model of Huntington\u2019s disease"],"prefix":"10.1186","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7611-3966","authenticated-orcid":false,"given":"Tamara","family":"Vasilkovska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somaie","family":"Salajeghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verdi","family":"Vanreusel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Van Audekerke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlies","family":"Verschuuren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydiane","family":"Hirschler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Warnking","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Pintelon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorian","family":"Pustina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Cachope","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ladislav","family":"Mrzljak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Mu\u00f1oz-Sanjuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel L.","family":"Barbier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winnok H.","family":"De Vos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemie","family":"Van der Linden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen","family":"Verhoye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"issue":"7321","key":"1028_CR1","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/nature09613","volume":"468","author":"D Attwell","year":"2010","unstructured":"Attwell D, Buchan AM, Charpak S, Lauritzen M, Macvicar BA, Newman EA. 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