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Analysis of ischemic stroke-mediated effects on blood-brain barrier properties along the arteriovenous axis assessed by intravital two-photon imaging
Early breach of the blood-brain barrier (BBB) and consequently extravasation of blood-borne substances into the brain parenchyma is a common hallmark of ischemic stroke. Although BBB breakdown is associated with an increased risk of cerebral hemorrhage and poor clinical prognosis, the cause and mech...
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Published in: | Fluids and barriers of the CNS 2024-04, Vol.21 (1), p.35-35, Article 35 |
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description | Early breach of the blood-brain barrier (BBB) and consequently extravasation of blood-borne substances into the brain parenchyma is a common hallmark of ischemic stroke. Although BBB breakdown is associated with an increased risk of cerebral hemorrhage and poor clinical prognosis, the cause and mechanism of this process are largely unknown. The aim of this study was to establish an imaging and analysis protocol which enables investigation of the dynamics of BBB breach in relation to hemodynamic properties along the arteriovenous axis. Using longitudinal intravital two-photon imaging following photothrombotic induction of ischemic stroke through a cranial window, we were able to study the response of the cerebral vasculature to ischemia, from the early critical hours to the days/weeks after the infarct. We demonstrate that disruption of the BBB and hemodynamic parameters, including perturbed blood flow, can be studied at single-vessel resolution in the three-dimensional space as early as 30 min after vessel occlusion. Further, we show that this protocol permits longitudinal studies on the response of individual blood vessels to ischemia over time, thus enabling detection of (maladaptive) vascular remodeling such as intussusception, angiogenic sprouting and entanglement of vessel networks. Taken together, this in vivo two-photon imaging and analysis protocol will be useful in future studies investigating the molecular and cellular mechanisms, and the spatial contribution, of BBB breach to disease progression which might ultimately aid the development of new and more precise treatment strategies for ischemic stroke. |
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Although BBB breakdown is associated with an increased risk of cerebral hemorrhage and poor clinical prognosis, the cause and mechanism of this process are largely unknown. The aim of this study was to establish an imaging and analysis protocol which enables investigation of the dynamics of BBB breach in relation to hemodynamic properties along the arteriovenous axis. Using longitudinal intravital two-photon imaging following photothrombotic induction of ischemic stroke through a cranial window, we were able to study the response of the cerebral vasculature to ischemia, from the early critical hours to the days/weeks after the infarct. We demonstrate that disruption of the BBB and hemodynamic parameters, including perturbed blood flow, can be studied at single-vessel resolution in the three-dimensional space as early as 30 min after vessel occlusion. Further, we show that this protocol permits longitudinal studies on the response of individual blood vessels to ischemia over time, thus enabling detection of (maladaptive) vascular remodeling such as intussusception, angiogenic sprouting and entanglement of vessel networks. Taken together, this in vivo two-photon imaging and analysis protocol will be useful in future studies investigating the molecular and cellular mechanisms, and the spatial contribution, of BBB breach to disease progression which might ultimately aid the development of new and more precise treatment strategies for ischemic stroke.</description><identifier>ISSN: 2045-8118</identifier><identifier>EISSN: 2045-8118</identifier><identifier>DOI: 10.1186/s12987-024-00537-5</identifier><identifier>PMID: 38622710</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Angiogenesis ; Arteriovenous axis ; Blood flow ; Blood vessels ; Blood-brain barrier ; Blood-Brain Barrier - metabolism ; Blood–brain barrier breach ; Brain Ischemia - diagnostic imaging ; Brain Ischemia - metabolism ; Brain research ; Cerebral blood flow ; Dental cement ; Extravasation ; Hemorrhage ; Humans ; Intussusception ; Ischemia ; Ischemia - metabolism ; Ischemic Stroke ; Laboratory animals ; Longitudinal imaging ; Magnetic resonance imaging ; Medicin och hälsovetenskap ; Microscopy ; Neuroimaging ; Parenchyma ; Prognosis ; Stroke ; Stroke - metabolism ; Two-photon microscopy ; Vascular remodeling</subject><ispartof>Fluids and barriers of the CNS, 2024-04, Vol.21 (1), p.35-35, Article 35</ispartof><rights>2024. 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Although BBB breakdown is associated with an increased risk of cerebral hemorrhage and poor clinical prognosis, the cause and mechanism of this process are largely unknown. The aim of this study was to establish an imaging and analysis protocol which enables investigation of the dynamics of BBB breach in relation to hemodynamic properties along the arteriovenous axis. Using longitudinal intravital two-photon imaging following photothrombotic induction of ischemic stroke through a cranial window, we were able to study the response of the cerebral vasculature to ischemia, from the early critical hours to the days/weeks after the infarct. We demonstrate that disruption of the BBB and hemodynamic parameters, including perturbed blood flow, can be studied at single-vessel resolution in the three-dimensional space as early as 30 min after vessel occlusion. Further, we show that this protocol permits longitudinal studies on the response of individual blood vessels to ischemia over time, thus enabling detection of (maladaptive) vascular remodeling such as intussusception, angiogenic sprouting and entanglement of vessel networks. 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Although BBB breakdown is associated with an increased risk of cerebral hemorrhage and poor clinical prognosis, the cause and mechanism of this process are largely unknown. The aim of this study was to establish an imaging and analysis protocol which enables investigation of the dynamics of BBB breach in relation to hemodynamic properties along the arteriovenous axis. Using longitudinal intravital two-photon imaging following photothrombotic induction of ischemic stroke through a cranial window, we were able to study the response of the cerebral vasculature to ischemia, from the early critical hours to the days/weeks after the infarct. We demonstrate that disruption of the BBB and hemodynamic parameters, including perturbed blood flow, can be studied at single-vessel resolution in the three-dimensional space as early as 30 min after vessel occlusion. Further, we show that this protocol permits longitudinal studies on the response of individual blood vessels to ischemia over time, thus enabling detection of (maladaptive) vascular remodeling such as intussusception, angiogenic sprouting and entanglement of vessel networks. Taken together, this in vivo two-photon imaging and analysis protocol will be useful in future studies investigating the molecular and cellular mechanisms, and the spatial contribution, of BBB breach to disease progression which might ultimately aid the development of new and more precise treatment strategies for ischemic stroke.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>38622710</pmid><doi>10.1186/s12987-024-00537-5</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Angiogenesis Arteriovenous axis Blood flow Blood vessels Blood-brain barrier Blood-Brain Barrier - metabolism Blood–brain barrier breach Brain Ischemia - diagnostic imaging Brain Ischemia - metabolism Brain research Cerebral blood flow Dental cement Extravasation Hemorrhage Humans Intussusception Ischemia Ischemia - metabolism Ischemic Stroke Laboratory animals Longitudinal imaging Magnetic resonance imaging Medicin och hälsovetenskap Microscopy Neuroimaging Parenchyma Prognosis Stroke Stroke - metabolism Two-photon microscopy Vascular remodeling |
title | Analysis of ischemic stroke-mediated effects on blood-brain barrier properties along the arteriovenous axis assessed by intravital two-photon imaging |
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