scholarly journals Therapeutic Modulation of Cerebral Microhemorrhage in a Mouse Model of Cerebral Amyloid Angiopathy

Stroke ◽  
2011 ◽  
Vol 42 (11) ◽  
pp. 3300-3303 ◽  
Author(s):  
Mark Fisher ◽  
Vitaly Vasilevko ◽  
Giselle F. Passos ◽  
Christopher Ventura ◽  
Daniel Quiring ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Cerebral Microhemorrhage ◽  
Cerebral Amyloid

Abstract WP397: Longitudinal Sex Differences in Cerebral Amyloid Angiopathy

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Michael Maniskas ◽  
Jacob Hudobenko ◽  
Akhiko Urayama ◽  
Louise McCullough ◽  
Bharti Manwani
Keyword(s):  
Mouse Model ◽  
Cerebral Amyloid Angiopathy ◽  
Cognitive Deficits ◽  
Elderly Women ◽  
Amyloid Plaque ◽  
Amyloid Angiopathy ◽  
Female Mice ◽  
Plaque Deposition ◽  
Significant Difference ◽  
Cerebral Amyloid

Background: Cerebral amyloid angiopathy (CAA) is the most common cause of lobar intracerebral hemorrhage in the aging population. It is mostly a consequence of amyloid beta40 (Aβ40) deposition within the cerebral blood vessels. A recent study has shown that this amyloid plaque deposition is more prevalent in the brain of elderly women compared to men. The increase in amyloid plaque deposition is linked to increased cerebral microbleeds (CMBs) and reduced cognition. The major objective of this study to discern if a sexual dichotomy existed in CMBs and cognition using mouse model of CAA. Methods: We used the Tg-SwDI mouse (“CAA mouse”, harboring Swedish, Dutch, and Iowa mutations of human amyloid precursor protein) model that develops Aβ deposits and cognitive deficits at 3-4 months. Cognitive deficits were analyzed using Fear Conditioning (FC) in pre-symptomatic (3 month) and (12 month) old male and female mice. Briefly, mice were acclimated to the FC chamber for a 2 minute training trial to record baseline. After 1 hour rest, mice were placed back in the chamber for 2 minutes, where they received a 2 millisecond shock (1,000 u/amp). Day 2, activity was recorded for 3 minutes and this measure was compared to baseline to determine Mean Inactive State (MIS-seconds). Mice were euthanized following FC, and brains scanned ex vivo using a MRI T2 Star sequence to assess for CMBs. Results: FC showed a significant difference in MIS (p<0.05) between male (3 and 12 months old) and female (3 months only) mice, n=6/group, suggesting that aged females had significantly lower MIS (Figure 1). MRI showed that aged female mice had more CMBs compared to aged male mice (females, 15.3±7 vs. males 0.25 ±0.2, n= 3/group, p=0.05. Conclusion: In a mouse model of CAA, our results demonstrate that aged females have increased CMBs as compared to males, which may be contributing to decreased cognition as seen on FC. Ongoing studies are designed to further understand the etiology of this sex difference.

P3-464: CARBONIC ANHYDRASE INHIBITORS AMELIORATE NEUROVASCULAR DYSFUNCTION IN A MOUSE MODEL OF CEREBRAL AMYLOID ANGIOPATHY

2006 ◽  
Vol 14 (7S_Part_24) ◽  
pp. P1296-P1296 ◽  
Author(s):  
Federica Angiulli ◽  
Maria E. Solesio ◽  
Ludovic Debure ◽  
Jaime Ramos Cejudo ◽  
Thomas Wisniewski ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Mouse Model ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Carbonic Anhydrase Inhibitors ◽  
Cerebral Amyloid ◽  
Neurovascular Dysfunction

scholarly journals Age-Dependent Neurovascular Dysfunction and Damage in a Mouse Model of Cerebral Amyloid Angiopathy

Stroke ◽  
2014 ◽  
Vol 45 (6) ◽  
pp. 1815-1821 ◽  
Author(s):  
Laibaik Park ◽  
Kenzo Koizumi ◽  
Sleiman El Jamal ◽  
Ping Zhou ◽  
Mary Lou Previti ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Age Dependent ◽  
Cerebral Amyloid ◽  
Neurovascular Dysfunction

scholarly journals Environmental Enrichment: Disentangling the Influence of Novelty, Social, and Physical Activity on Cerebral Amyloid Angiopathy in a Transgenic Mouse Model

2020 ◽  
Vol 21 (3) ◽  
pp. 843
Author(s):  
Lisa S. Robison ◽  
Nikita Francis ◽  
Dominique L. Popescu ◽  
Maria E. Anderson ◽  
Joshua Hatfield ◽  
...  
Keyword(s):  
Physical Activity ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Cerebral Amyloid Angiopathy ◽  
Environmental Enrichment ◽  
Transgenic Mouse Model ◽  
Cognitive Stimulation ◽  
Cognitive Behavioral ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid

Cerebral amyloid angiopathy (CAA) is the deposition of amyloid protein in the cerebral vasculature, a common feature in both aging and Alzheimer’s disease (AD). However, the effects of environmental factors, particularly cognitive stimulation, social stimulation, and physical activity, on CAA pathology are poorly understood. These factors, delivered in the form of the environmental enrichment (EE) paradigm in rodents, have been shown to have beneficial effects on the brain and behavior in healthy aging and AD models. However, the relative importance of these subcomponents on CAA pathology has not been investigated. Therefore, we assessed the effects of EE, social enrichment (SOC), and cognitive enrichment (COG) compared to a control group that was single housed without enrichment (SIN) from 4 to 8 months of age in wild-type mice (WT) and Tg-SwDI mice, a transgenic mouse model of CAA that exhibits cognitive/behavioral deficits. The results show that individual facets of enrichment can affect an animal model of CAA, though the SOC and combined EE conditions are generally the most effective at producing physiological, cognitive/behavioral, and neuropathological changes, adding to a growing literature supporting the benefits of lifestyle interventions.

scholarly journals Reduced nitric oxide bioavailability mediates cerebroarterial dysfunction independent of cerebral amyloid angiopathy in a mouse model of Alzheimer’s disease

2017 ◽  
Vol 312 (2) ◽  
pp. H232-H238 ◽  
Author(s):  
Mario Merlini ◽  
Yi Shi ◽  
Stephan Keller ◽  
Gianluigi Savarese ◽  
Alexander Akhmedov ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Model Of Alzheimer’S Disease ◽  
No Bioavailability ◽  
Cerebral Amyloid ◽  
Ad Mouse Model

In Alzheimer’s disease (AD), cerebral arteries, in contrast to cerebral microvessels, show both cerebral amyloid angiopathy (CAA) -dependent and -independent vessel wall pathology. However, it remains unclear whether CAA-independent vessel wall pathology affects arterial function, thereby chronically reducing cerebral perfusion, and, if so, which mechanisms mediate this effect. To this end, we assessed the ex vivo vascular function of the basilar artery and a similar-sized peripheral artery (femoral artery) in the Swedish-Arctic (SweArc) transgenic AD mouse model at different disease stages. Furthermore, we used quantitative immunohistochemistry to analyze CAA, endothelial morphology, and molecular pathways pertinent to vascular relaxation. We found that endothelium-dependent, but not smooth muscle-dependent, vasorelaxation was significantly impaired in basilar and femoral arteries of 15-mo-old SweArc mice compared with that of age-matched wild-type and 6-mo-old SweArc mice. This impairment was accompanied by significantly reduced levels of cyclic GMP, indicating a reduced nitric oxide (NO) bioavailability. However, no age- and genotype-related differences in oxidative stress as measured by lipid peroxidation were observed. Although parenchymal capillaries, arterioles, and arteries showed abundant CAA in the 15-mo-old SweArc mice, no CAA or changes in endothelial morphology were detected histologically in the basilar and femoral artery. Thus our results suggest that, in this AD mouse model, dysfunction of large intracranial, extracerebral arteries important for brain perfusion is mediated by reduced NO bioavailability rather than by CAA. This finding supports the growing body of evidence highlighting the therapeutic importance of targeting the cerebrovasculature in AD. NEW & NOTEWORTHY We show that vasorelaxation of the basilar artery, a large intracranial, extracerebral artery important for cerebral perfusion, is impaired independent of cerebral amyloid angiopathy in a transgenic mouse model of Alzheimer’s disease. Interestingly, this dysfunction is specifically endothelium related and is mediated by impaired nitric oxide–cyclic GMP bioavailability. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/cerebroarterial-dysfunction-in-swedish-arctic-ad-mice/ .

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