Cerebral Venous Collagen Remodeling in a Modified White Matter Lesions Animal Model

Lin, Jing; Lan, Linfang; Wang, Dilong; Qiu, Baoshan; Fan, Yuhua

doi:10.1016/j.neuroscience.2017.10.031

Cited by 15 publications

(10 citation statements)

References 31 publications

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“…At least three random fields of each part were selected and photographed for further analysis. The cerebral small arteries (10-65 μm) were indicated by immunostaining for αSMA [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

“…Studies have shown that RHRsp rats presented cerebral small artery remodeling with fibrinoid necrosis, hyalinosis, and apparent luminal narrowing [ 17 ]. Behavioral tests have also confirmed cognitive impairment in RHRsp [ 18 ]. These results suggest that RHRsp is a relatively ideal animal model of CSVD, particularly for the study of vascular pathological changes in hypertension-associated CSVD.…”

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confidence: 99%

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EP3 Receptor Deficiency Improves Vascular Remodeling and Cognitive Impairment in Cerebral Small Vessel Disease

Liu¹,

Tang²,

Yang³

et al. 2022

Aging and disease

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Aging and hypertension are major risk factors for cerebral small vessel disease (CSVD). Anti-hypertensive therapy has achieved effective; however, incomplete results in treating CSVD, suggesting the need for additional treatments. Targeting abnormal inflammatory responses has become a topic of research interest. Small artery remodeling is the main pathological feature of CSVD. Inhibition of the E-prostanoid 3 (EP3) receptor has been shown to attenuate vascular remodeling in peripheral organs; however, little is known about its role in CSVD. Therefore, we investigated whether the deletion of EP3 attenuates the development of CSVD in an animal model-- stroke-prone renovascular hypertensive rat (RHRsp). We found that the cerebral small arteries of RHRsp exhibited increased EP3 expression. Despite no alleviation of hypertension, the deletion of EP3 still attenuated the cerebral small artery remodeling of RHRsp, as evidenced by reduced overexpression of extracellular matrix (ECM) in the vessel. In vitro experiments indicated that EP3 deletion regulated the expression of ECM by downregulating TGF-β1/Smad signaling. Furthermore, the Morris water maze test and magnetic resonance test demonstrated that EP3 knockout attenuated cognitive impairment of the RHRsp, possibly through increased cerebral blood flow. Together, our results indicate that the deletion of EP3 attenuates vascular remodeling and vascular cognitive impairment induced by hypertension, and blockade of the EP3 receptor may be a promising strategy for the treatment of CSVD.

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“…At least three random fields of each part were selected and photographed for further analysis. The cerebral small arteries (10-65 μm) were indicated by immunostaining for αSMA [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

EP3 Receptor Deficiency Improves Vascular Remodeling and Cognitive Impairment in Cerebral Small Vessel Disease

Liu¹,

Tang²,

Yang³

et al. 2022

Aging and disease

View full text Add to dashboard Cite

show abstract

“…Studies have shown that RHRsp rats presented cerebral small artery remodeling with brinoid necrosis, hyalinosis, and apparent luminal narrowing [18]. Behavioral tests also con rmed cognitive impairment in RHRsp [19]. These results suggest that RHRsp is a relatively ideal animal model of CSVD, especially for the study of vascular pathological changes in hypertension-associated CSVD.…”

Section: Introductionmentioning

confidence: 71%

“…At least three random elds of each part were selected and photographed for further analysis. The cerebral small arteries (10-65μm) were indicated by the immunostaining of αSMA [19]. The detailed methods are provided in the Supplementary Material.…”

Section: Immuno Uorescencementioning

confidence: 99%

EP3 Receptor Deficiency Attenuates Vascular Remodeling and Cognitive Impairment in a Cerebral Small Vessel Disease Model

Liu

Tang

Yang

et al. 2020

Preprint

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BackgroundAnti-hypertensive therapy has achieved effective but not complete results in treating cerebral small vessel disease (CSVD), suggesting the necessity for additional treatments. Targeting abnormal inflammatory responses has become a research interest. Inhibition of E-prostanoid 3(EP3) receptor has been shown to attenuate vascular remodeling in peripheral organs, but little is known about its role in CSVD. Here, we investigated whether the deletion of EP3 attenuates the development of CSVD.MethodsStroke-prone renovascular hypertensive rat (RHRsp) was used as an animal model of CSVD. The effect of EP3 deletion on the expression of extracellular matrix (ECM) in cerebral small arteries of RHRsp was detected by immunofluorescence. Changes in cognitive function and cerebral blood flow (CBF) of RHRsp were evaluated using the Morris water maze test and MRI. In vitro experiments with primary rat brain microvascular smooth muscle cells were used to confirm whether the transforming growth factor beta 1 (TGF-β1) signal takes part in the processResultsCerebral small arteries of RHRsp exhibited increased EP3 expression. Despite no alleviation in hypertension, the deletion of EP3 still reduced the overexpression of ECM in the cerebral small arteries of RHRsp. In vitro experiments indicated that EP3 deletion regulated the expression of ECM by downregulating TGF-β1/Smad signaling. EP3 knockout further attenuated the cognitive impairment of the RHRsp possibly through increased CBF. ConclusionTogether, our results indicate that the deletion of EP3 attenuates the vascular remodeling and vascular cognitive impairment induced by hypertension, and blockade of the EP3 receptor may be a promising strategy for the treatment of CSVD.

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“…VC in small veins, deposition of collagen I and collagen IV, leading to white matter changes, was described in modified 2-vessel occlusion and hypertensive rats [22]. Venules can be differentiated from arterioles by α-smooth muscle actin staining.…”

Section: Animal Studiesmentioning

confidence: 97%

Potential Mechanism of Venous System for Leukoaraiosis: From post-mortem to in vivo Research

et al. 2019

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Background: Leukoaraiosis (LA), widely accepted as a feature of cerebral small vessel disease, significantly increases the incidence of stroke, dementia, and death. Cerebral small artery disease has been considered as one of the main causes of LA. However, since the term "venous collagenosis" (VC) was proposed in an atrophy research in 1995, there have been pathological and neuroimaging studies proving the association between the venous system and LA in aging, Alzheimer's disease (AD), and Parkinson's disease. Summary: Autopsy studies confirmed that thickening of the lumen wall in venules, which results from the deposition of collagen I and III, leading to vessel stenosis or occlusion, is closely associated with LA. Susceptibility-weighted imaging research revealed a controversial association of deep medullary veins and LA in vivo, regarding which there are no standard criteria currently. Nevertheless, retinal venous changes had been reported to increase the risk of LA development, providing a novel way for in vivo evaluation. As for the internal jugular vein, jugular venous reflux could double the LA score in aging and modulate circulation of cerebral spinal fluids. Key Messages: Disruption of the venous system was notably associated with LA in aging, AD, and Parkinson's disease postmortem and in in vivo models. The venous pathological changes may induce cerebral hypoperfusion, drainage system disruption, and vasogenic oedema in the veins around the periventricular white matter. The clarification of VC in LA may provide an early prevention and early treatment strategy for LA patients.

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Cerebral Venous Collagen Remodeling in a Modified White Matter Lesions Animal Model

Cited by 15 publications

References 31 publications

EP3 Receptor Deficiency Improves Vascular Remodeling and Cognitive Impairment in Cerebral Small Vessel Disease

EP3 Receptor Deficiency Improves Vascular Remodeling and Cognitive Impairment in Cerebral Small Vessel Disease

EP3 Receptor Deficiency Attenuates Vascular Remodeling and Cognitive Impairment in a Cerebral Small Vessel Disease Model

Potential Mechanism of Venous System for Leukoaraiosis: From post-mortem to in vivo Research

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