Faculty Opinions recommendation of In vivo characterization of spontaneous microhemorrhage formation in mice with cerebral amyloid angiopathy.

2021 ◽  
Author(s):  
Mark Fisher
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid ◽  
In Vivo Characterization

Abstract P342: Histopathological Correlates of MRI-Visible Perivascular Spaces in Cerebral Amyloid Angiopathy

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Valentina Perosa ◽  
Leon P Munting ◽  
Whitney Freeze ◽  
Ashley A Scherlek ◽  
Anand Viswanathan ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Cerebral Amyloid Angiopathy ◽  
Ex Vivo ◽  
Histopathological Examination ◽  
Amyloid Β ◽  
Amyloid Angiopathy ◽  
Perivascular Spaces ◽  
Cerebral Amyloid

Perivascular spaces (PVS) are fluid-filled spaces surrounding cerebral blood vessels. MRI-visible, supposedly enlarged, PVS in the centrum semiovale (CSO) have been associated with cerebral amyloid angiopathy (CAA). PVS enlargement may be due to perivascular clearance impairments, potentially caused by increased amyloid-β (Aβ) accumulation in the walls of vessels in the overlying cortex. We test this hypothesis, using MRI-guided histopathological examination of PVS in CAA autopsy cases. The cohort included 19 CAA (74.1±8.2y, 7F) and 5 non-CAA control cases (88.0±4.9y, 3F). Formalin-fixed hemispheres were scanned on a 3T MRI scanner, including a 500μm T2-weighted sequence. PVS enlargement was assessed in the CSO on in vivo and ex vivo MRI. In addition, local score of PVS enlargement was assessed in four pre-defined juxtacortical areas (Fig.A), using a semiquantitative score and on the corresponding histological sections (Fig.B). Severity of leptomeningeal and cortical CAA were assessed on adjacent Aβ-stained sections, using a semiquantitative scale.PVS enlargement was more severe in CAA cases compared to controls, both on in vivo and ex vivo MRI (p<0.05). PVS enlargement on ex vivo MRI positively correlated with the severity of PVS enlargement on the corresponding histopathological samples (Fig.C). Within CAA cases, the degree of PVS enlargement on ex vivo MRI was positively associated with leptomeningeal CAA severity (n=52 samples, ρ=0.35, p=0.011), but not cortical CAA severity (n=52 samples, ρ=0.10, p=0.472). These preliminary findings confirm that the degree of MRI-visible PVS in juxtacortical brain areas reflects enlargement on histopathology. Moreover, they suggest that PVS enlargement in cases with CAA corresponds to increased CAA severity in the overlying leptomeningeal vessels, possibly as a result of impaired perivascular clearance. Future directions include characterization of individual blood vessels associated with PVS enlargement.

P1-207: ENDOTHELIAL APP EXPRESSION LEADS TO CEREBRAL AMYLOID ANGIOPATHY IN VIVO

2006 ◽  
Vol 14 (7S_Part_6) ◽  
pp. P358-P358
Author(s):  
Shinobu Kitazume ◽  
Yuriko Tachida ◽  
Rie Imamaki ◽  
Yasuhiko Kizuka ◽  
Takashi Saito ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid

scholarly journals Antibody-Mediated Clearance of Amyloid-  Peptide from Cerebral Amyloid Angiopathy Revealed by Quantitative In Vivo Imaging

2007 ◽  
Vol 27 (8) ◽  
pp. 1973-1980 ◽  
Author(s):  
C. M. Prada ◽  
M. Garcia-Alloza ◽  
R. A. Betensky ◽  
S. X. Zhang-Nunes ◽  
S. M. Greenberg ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
In Vivo Imaging ◽  
Amyloid Peptide ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid

Abstract 62: Increased Monocyte/Macrophage Pro-Inflammatory Cytokines and Chemokines in Mice With Cerebral Amyloid Angiopathy

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Carson Finger ◽  
Juneyoung Lee ◽  
Diego Morales ◽  
Bharti Manwani
Keyword(s):  
Inflammatory Cytokines ◽  
Cerebral Amyloid Angiopathy ◽  
Neuronal Damage ◽  
Muscle Layer ◽  
Amyloid Angiopathy ◽  
Monocyte Chemoattractant Protein 1 ◽  
Cerebral Amyloid ◽  
The Brain ◽  
Pro Inflammatory Cytokines

Introduction: Cerebral amyloid angiopathy (CAA) is one of the common causes of intracerebral hemorrhage in the elderly. It is caused by the deposition of amyloid-beta1-40 (Aβ1-40) deposition within cerebral blood vessels, especially the smooth muscle layer, that can cause cerebral microbleeds (CMBs) and cognitive impairment. We hypothesize Aβ deposition causes an innate inflammatory response characterized by an increase and activation of microglia and macrophages. This inflammation might cause CMBs, neuronal damage and cognitive decline CAA. Methods: C57BL6 Tg-SwDI male and female mice (18 months) were used as a mouse model for CAA. Age-matched wild-type (WT) mice were used as controls. Brain samples from these mice were fractionated and 23-plex cytokine multiplex was performed on the brain lysates. Data was analyzed using two sample t-test or GraphPad PRISM. Results: Our data showed that CAA increased levels of pro-inflammatory cytokines in the brain, as compared with WT mice. Multiplex analysis showed that Tg-SwDI mice had significantly higher levels of cytokines; tumor necrosis factor-α (TNF-α; 54.38 vs. 17.03 pg/ml, p=0.00207), IL-12 (70.81 vs. 53.95 pg/ml, p= 0.014), macrophage inflammatory protein-1α (MIP-1α, 113.92 vs. 16.81 pg/ml, p=3.85E-10), MIP-1β (86.15 vs. 53.43 pg/ml, p= 3.51E-09) and monocyte chemoattractant protein-1 (MCP-1, 109.46 vs. 118.53 pg/ml, p= 0.00033). Conclusion: This study highlights a monocyte/macrophage driven pro-inflammatory milieu in CAA. Recent studies using in vivo two-photon imaging and histology have found recruitment of microglia and monocytes/macrophages around induced 100 μm sized hemorrhage. The increase in these microglia is only found in Alzheimer’s patients who also had CAA and was not seen in patients with no CAA, suggesting the role of microglia in causing vascular frailty in CAA. Our study suggests that pro-inflammatory cytokines like TNF-a, IL-12, MIP-1α, MIP-1β and MCP-1 can be therapeutic targets for CAA.

Abstract TMP109: Loss of Gray-White Contrast in Cerebral Amyloid Angiopathy: An in-vivo and Ex-Vivo Exploratory Approach

Stroke ◽  
2019 ◽  
Vol 50 (Suppl_1) ◽  
Author(s):  
Panagiotis Fotiadis ◽  
Susanne van Veluw ◽  
David Salat ◽  
Andrew Warren ◽  
Sarah Grill ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Ex Vivo ◽  
Amyloid Angiopathy ◽  
Exploratory Approach ◽  
Cerebral Amyloid

scholarly journals In vivo characterization of spontaneous microhemorrhage formation in mice with cerebral amyloid angiopathy

2020 ◽  
Vol 41 (1) ◽  
pp. 82-91 ◽  
Author(s):  
Susanne J van Veluw ◽  
Matthew P Frosch ◽  
Ashley A Scherlek ◽  
Daniel Lee ◽  
Steven M Greenberg ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Spatial Relationship ◽  
Amyloid Angiopathy ◽  
Vascular Networks ◽  
Complex Flow ◽  
Wild Type Littermate ◽  
Two Photon Microscopy ◽  
Heparin Administration ◽  
Cerebral Amyloid

The pathophysiology of microhemorrhages in the context of cerebral amyloid angiopathy (CAA) remains poorly understood. Here we used in vivo two-photon microscopy in aged APP/PS1 mice with mild-to-moderate CAA to assess the formation of microhemorrhages and their spatial relationship with vascular Aβ depositions in the surrounding microvascular network. Mice with chronic cranial windows were intravenously injected with fluorescent dextran to visualize the vessels and a fluorescently labeled anti-fibrin antibody to visualize microhemorrhages. Focal vessel irradiations resulted in extravascular fibrin-positive clots at individual rupture sites that remained visible for weeks. Spontaneous extravascular fibrin-positive clots were more often observed in 19-month-old transgenic APP/PS1 mice compared to their wild-type littermate controls ( p = 0.039), after heparin administration. In the transgenic mice, these spontaneous leakage sites frequently occurred at arteriolar segments without CAA at bifurcations or vessel bends. These findings suggest that the presence of vascular Aβ per se does not directly predispose vessels to leak, but that complex flow dynamics within CAA-affected vascular networks likely play a role. Our in vivo approach for the detection of individual spontaneous leakage sites may be used in longitudinal studies aimed to assess structural and functional alterations at the single-vessel level leading up to microhemorrhage formation.

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