{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T01:30:24Z","timestamp":1789695024032,"version":"4.0.1"},"reference-count":26,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T00:00:00Z","timestamp":1628208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHO1385\/1-1"],"award-info":[{"award-number":["SCHO1385\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Munich Cluster for Systems Neurology","award":["390857198"],"award-info":[{"award-number":["390857198"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Subarachnoid hemorrhage (SAH) is associated with acute and delayed cerebral ischemia. We suggested spasms of pial arterioles as a possible mechanism; however, it remained unclear whether and how pial microvasospasms (MVSs) induce cerebral ischemia. Therefore, we used in vivo deep tissue imaging by two-photon microscopy to investigate MVSs together with the intraparenchymal microcirculation in a clinically relevant murine SAH model. Male C57BL\/6 mice received a cranial window. Cerebral vessels and leukocytes were labelled with fluorescent dyes and imaged by in vivo two-photon microscopy before and three hours after SAH induced by filament perforation. After SAH, a large clot formed around the perforation site at the skull base, and blood distributed along the perivascular space of the middle cerebral artery up to the cerebral cortex. Comparing the cerebral microvasculature before and after SAH, we identified three different patterns of constrictions: pearl string, global, and bottleneck. At the same time, the volume of perfused intraparenchymal vessels and blood flow velocity in individual arterioles were significantly reduced by more than 60%. Plugging of capillaries by leukocytes was observed but infrequent. The current study demonstrates that perivascular blood is associated with spasms of pial arterioles and that these spasms result in a significant reduction in cortical perfusion after SAH. Thus, the pial microvasospasm seems to be an important mechanism by which blood in the subarachnoid space triggers cerebral ischemia after SAH. Identifying the mechanisms of pial vasospasm may therefore result in novel therapeutic options for SAH patients.<\/jats:p>","DOI":"10.3390\/ijms22168444","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T05:22:01Z","timestamp":1628227321000},"page":"8444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Role of Pial Microvasospasms and Leukocyte Plugging for Parenchymal Perfusion after Subarachnoid Hemorrhage Assessed by In Vivo Multi-Photon Microscopy"],"prefix":"10.3390","volume":"22","author":[{"given":"Julian","family":"Schwarting","sequence":"first","affiliation":[{"name":"Institute for Stroke and Dementia Research, Munich University Hospital, Graduate School of Systemic Neurosciences, Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-University, 81377 Munich, Germany"},{"name":"Department of Neurosurgery, Munich University Hospital, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Nehrkorn","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, Munich University Hospital, Graduate School of Systemic Neurosciences, Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-University, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanhan","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, Munich University Hospital, Graduate School of Systemic Neurosciences, Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-University, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus","family":"Plesnila","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, Munich University Hospital, Graduate School of Systemic Neurosciences, Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-University, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole Angela","family":"Terpolilli","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, Munich University Hospital, Graduate School of Systemic Neurosciences, Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-University, 81377 Munich, Germany"},{"name":"Department of Neurosurgery, Munich University Hospital, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1179\/016164106X114991","article-title":"Mechanisms of acute brain injury after subarachnoid hemorrhage","volume":"28","author":"Sehba","year":"2006","journal-title":"Neurol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1089\/neu.2009.0924","article-title":"Acute hypoperfusion immediately after subarachnoid hemorrhage: A xenon contrast-enhanced CT study","volume":"26","author":"Schubert","year":"2009","journal-title":"J. Neurotrauma"},{"key":"ref_3","first-page":"35","article-title":"Hypoperfusion in the acute phase of subarachnoid hemorrhage","volume":"110","author":"Schubert","year":"2011","journal-title":"Acta Neurochir. Suppl."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1136\/jnnp-2014-307711","article-title":"The pathophysiology and treatment of delayed cerebral ischaemia following subarachnoid haemorrhage","volume":"85","author":"Budohoski","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/978-3-7091-1192-5_37","article-title":"Cerebral microvasculature is an early target of subarachnoid hemorrhage","volume":"115","author":"Sehba","year":"2013","journal-title":"Acta Neurochir. Suppl."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.pneurobio.2012.02.003","article-title":"The importance of early brain injury after subarachnoid hemorrhage","volume":"97","author":"Sehba","year":"2012","journal-title":"Prog. Neurobiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1227\/01.NEU.0000065154.04824.9E","article-title":"Intraoperative detection of early microvasospasm in patients with subarachnoid hemorrhage by using orthogonal polarization spectral imaging","volume":"52","author":"Uhl","year":"2003","journal-title":"Neurosurgery"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1161\/01.STR.0000126039.91400.cb","article-title":"Direct observation of the human cerebral microcirculation during aneurysm surgery reveals increased arteriolar contractility","volume":"35","author":"Pennings","year":"2004","journal-title":"Stroke"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/jcbfm.2011.154","article-title":"Experimental subarachnoid hemorrhage causes early and long-lasting microarterial constriction and microthrombosis: An in-vivo microscopy study","volume":"32","author":"Friedrich","year":"2012","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s10571-008-9316-8","article-title":"Dynamic alterations of cerebral pial microcirculation during experimental subarachnoid hemorrhage","volume":"29","author":"Sun","year":"2009","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"456","DOI":"10.4103\/1673-5374.228728","article-title":"In vivo observation of cerebral microcirculation after experimental subarachnoid hemorrhage in mice","volume":"13","author":"Yang","year":"2018","journal-title":"Neural. Regen. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1177\/0271678X15605848","article-title":"Nitric oxide inhalation reduces brain damage, prevents mortality, and improves neurological outcome after subarachnoid hemorrhage by resolving early pial microvasospasms","volume":"36","author":"Terpolilli","year":"2016","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3171\/jns.2007.106.2.321","article-title":"Acute cerebral vascular injury after subarachnoid hemorrhage and its prevention by administration of a nitric oxide donor","volume":"106","author":"Sehba","year":"2007","journal-title":"J. Neurosurg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1097\/00004647-200003000-00018","article-title":"Acute decrease in cerebral nitric oxide levels after subarachnoid hemorrhage","volume":"20","author":"Sehba","year":"2000","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_15","unstructured":"Suzuki, H., Kanamaru, H., Kawakita, F., Asada, R., Fujimoto, M., and Shiba, M. (2020). Cerebrovascular pathophysiology of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Histol. Histopathol., 18253."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"309","DOI":"10.2176\/nmc.30.309","article-title":"Cerebral microthrombosis in symptomatic cerebral vasospasm\u2014A quantitative histological study in autopsy cases","volume":"30","author":"Suzuki","year":"1990","journal-title":"Neurol. Med. Chir."},{"key":"ref_17","first-page":"49","article-title":"Early micro vascular changes after subarachnoid hemorrhage","volume":"110","author":"Sehba","year":"2011","journal-title":"Acta Neurochir. Suppl."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s12975-014-0323-4","article-title":"Subarachnoid hemorrhage: A review of experimental studies on the microcirculation and the neurovascular unit","volume":"5","author":"Tso","year":"2014","journal-title":"Transl. Stroke Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1161\/STROKEAHA.107.487827","article-title":"Subtype activation and interaction of protein kinase C and mitogen-activated protein kinase controlling receptor expression in cerebral arteries and microvessels after subarachnoid hemorrhage","volume":"39","author":"Ansar","year":"2008","journal-title":"Stroke"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1177\/0271678X19841443","article-title":"Systemic inflammation in hemorrhagic strokes\u2014A novel neurological sign and therapeutic target?","volume":"39","author":"Saand","year":"2019","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1227\/01.NEU.0000337579.05110.F4","article-title":"Platelet and leukocyte adhesion in the microvasculature at the cerebral surface immediately after subarachnoid hemorrhage","volume":"64","author":"Ishikawa","year":"2009","journal-title":"Neurosurgery"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e12516","DOI":"10.1111\/micc.12516","article-title":"Capillary flow disturbances after experimental subarachnoid hemorrhage: A contributor to delayed cerebral ischemia?","volume":"26","author":"Anzabi","year":"2019","journal-title":"Microcirculation"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kilkenny, C., Browne, W.J., Cuthill, I.C., Emerson, M., and Altman, D.G. (2010). Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research. PLoS Biol., 8.","DOI":"10.1371\/journal.pbio.1000412"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jneumeth.2010.05.005","article-title":"Standardized induction of subarachnoid hemorrhage in mice by intracranial pressure monitoring","volume":"190","author":"Feiler","year":"2010","journal-title":"J. Neurosci. Methods"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Liu, H., Dienel, A., Scholler, K., Schwarzmaier, S.M., Nehrkorn, K., Plesnila, N., and Terpolilli, N.A. (2018). Microvasospasms After Experimental Subarachnoid Hemorrhage Do Not Depend on Endothelin A Receptors. Stroke.","DOI":"10.1161\/STROKEAHA.117.020028"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lenz, I.J., Plesnila, N., and Terpolilli, N.A. (2020). Role of endothelial nitric oxide synthase for early brain injury after subarachnoid hemorrhage in mice. J. Cereb. Blood Flow Metab.","DOI":"10.1177\/0271678X20973787"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8444\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:41:27Z","timestamp":1760164887000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,6]]},"references-count":26,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22168444"],"URL":"https:\/\/doi.org\/10.3390\/ijms22168444","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,6]]}}}