scholarly journals Zebrafish Models of Cerebrovascular Disease

2014 ◽  
Vol 34 (4) ◽  
pp. 571-577 ◽  
Author(s):  
Brian P Walcott ◽  
Randall T Peterson

Perturbations in cerebral blood flow and abnormalities in blood vessel structure are the hallmarks of cerebrovascular disease. While there are many genetic and environmental factors that affect these entities through a heterogeneous group of disease processes, the ultimate final pathologic insult in humans is defined as a stroke, or damage to brain parenchyma. In the case of ischemic stroke, blood fails to reach its target destination whereas in hemorrhagic stroke, extravasation of blood occurs outside of the blood vessel lumen, resulting in direct damage to brain parenchyma. As these acute events can be neurologically devastating, if not fatal, development of novel therapeutics are urgently needed. The zebrafish ( Danio rerio) is an attractive model for the study of cerebrovascular disease because of its morphological and physiological similarity to human cerebral vasculature, its ability to be genetically manipulated, and its fecundity allowing for large-scale, phenotype-based screens.

BioEssays ◽  
2013 ◽  
Vol 36 (3) ◽  
pp. 251-259 ◽  
Author(s):  
Marta S. Charpentier ◽  
Frank L. Conlon

2007 ◽  
Vol 293 (4) ◽  
pp. R1754-R1763 ◽  
Author(s):  
Christiné S. Rigsby ◽  
Ashley E. Burch ◽  
Safia Ogbi ◽  
David M. Pollock ◽  
Anne M. Dorrance

Data from the Framingham Heart Study suggest that women may be more sensitive to the deleterious cardiovascular remodeling effects of aldosterone. Previous studies from our laboratory have shown that chronic treatment with spironolactone, a mineralocorticoid receptor (MR) antagonist, decreases ischemic cerebral infarct size and prevents remodeling of the middle cerebral artery (MCA) in male spontaneously hypertensive stroke-prone rats (SHRSP). Therefore, we hypothesized that MR antagonism would reduce ischemic infarct size and prevent MCA remodeling in female SHRSP. Six-week-old female SHRSP were treated for 6 wk with spironolactone (25 or 50 mg·kg−1·day−1) or eplerenone (100 mg·kg−1·day−1) and compared with untreated controls. At 12 wk, cerebral ischemia was induced for 18 h using the intraluminal suture occlusion technique, or the MCA was isolated for analysis of passive structure using a pressurized arteriograph. MR antagonism had no effect on infarct size or passive MCA structure in female SHRSP. To study the potential effects of estrogen, the above experiments were repeated in bilaterally ovariectomized (OVX) female SHRSP treated with spironolactone (25 mg·kg−1·day−1). Infarct size and vessel structure in OVX SHRSP were not different from control SHRSP. Spironolactone had no effect on infarct size in OVX SHRSP. However, MCA lumen and outer diameters were increased in spironolactone-treated OVX SHRSP, suggesting an effect of estrogen. Cerebral artery MR expression, assessed by Western blotting, was increased in female, compared with male, SHRSP. These studies highlight an apparent sexual dimorphism of MR expression and activity in the cerebral vasculature from hypertensive rats.


Author(s):  
Krishna Madhavan ◽  
Walter Bonani ◽  
Craig Lanning ◽  
Wei Tan

Vascular grafts are currently used to treat cardiovascular diseases such as arthrosclerosis by bypass surgery and as vascular access in hemodialysis [1]. There are a number of types of grafts including autologous vessels (such saphenous vein), synthetic grafts (such as expanded polytetrafluoroethylene) and tissue engineered blood vessels. Currently synthetic grafts are most commonly used as blood vessel replacements and there are a number of problems associated with them. One main impediment is that these grafts are not suitable for small-diameter (less than 6mm) vessel replacement [1, 2], due to high occlusion rates. The major concern over the other alternatives such as autologous vessels and tissue engineered products is their availability. Thus, new approaches to constructing biomimetic small-diameter blood vessel equivalents, that are immediately available, may address the unmet demand in this area. Therefore, we have designed a novel bilayer vascular construct which is made up of a nanofibrous intimal-equivalent as thromboresistant vessel lumen and a mimetic extracellular matrix (ECM) as medial-equivalent for smooth muscle cells (SMC) from native artery to invade and remodel the ECM.


2020 ◽  
Vol 1 (2) ◽  
pp. 49
Author(s):  
Hijriyah Putri Tarmizi Hasibuan ◽  
Isra Thristy

Background: Stroke is the second largest cause of death in the world. Stroke is classified based on its etiology as ischemic stroke and hemorrhagic stroke. Most large-scale studies on the risk of total cholesterol and triglyceride levels in stroke are not distinguished between ischemic and hemorrhagic strokes. Purposes: The purpose of this study was to determine the comparison of triglyceride and total cholesterol levels in ischemic stroke patients with hemorrhagic stroke. Method: Descriptive analytic study using medical records of patients at Medan Haji General Hospital in 2018-2019. The number of ischemic stroke patients is 28 patients and hemorrhagic stroke 28 patients with a total sample of 56 patients. Results: In ischemic stroke patients, the average value of triglyceride levels was 144.75 mg/dL and the average value of total cholesterol was 250.93 mg/dL. In hemorrhagic stroke patients, the average value of triglyceride levels is 126.93 mg/dL and the average total cholesterol level is 174.25 mg/dL. Conclusion: From this study we found a significant difference in total cholesterol between ischemic and hemorrhagic strokes. No significant difference was found in triglycerides between ischemic and hemorrhagic strokes.


2020 ◽  
Author(s):  
Joungyoun Kim ◽  
Hyeong-Seop Kim ◽  
Yun-Jong Bae ◽  
Hyeong-Chul Lee ◽  
Jae-woo Lee ◽  
...  

Abstract Background Statins have been recommended for use in atherosclerotic cardio-cerebrovascular disease (CCVD). The purpose of this study was to investigate the efficacy of five different types of statin in the secondary prevention of CCVD in patients. Methods This study has a retrospective design and utilised data from the Korean National Health Insurance Service-National Health Screening Cohort. Participants aged 40 to 69 years at baseline were categorized into five statin groups (atorvastatin, rosuvastatin, pitavastatin, simvastatin, and pravastatin). The primary composite outcome was defined as recurrence of CCVD or all causes of death. Cox proportional hazard regression models were adopted after stepwise adjustments for confounders to investigate the difference in efficacy among the different statins. Results Of the 755 final study participants (485: atorvastatin, 34: pitavastatin, 8: pravastatin, 96: rosuvastatin, and 132: simvastatin group), 48 patients experienced primary composite outcomes. The median follow-up duration was 12.4 years across all groups. After stepwise adjustments, the hazard ratios (95% confidence intervals) for primary composite outcomes of atorvastatin, pitavastatin, and rosuvastatin groups were 0.956 (0.456–2.005), 1.347 (0.354–5.116), and 0.943 (0.317–2.803), respectively, when compared with the simvastatin group. Conclusions There were no significant differences between the statins in their efficacy for preventing recurrence of CCVD events and/or death in CCVD patients. However, further large-scale clinical trials are required to confirm these results.


1999 ◽  
Vol 17 (2) ◽  
pp. 257-266 ◽  
Author(s):  
Chun Yuan ◽  
Eugene Lin ◽  
Jacob Millard ◽  
Jenq–Neng Hwang

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Julia E Slocomb ◽  
Mary E Lott ◽  
Vikram Shivkumar ◽  
Kerstin Bettermann

The eye and the brain share embryological, anatomic and physiological similarities, which suggest that the retinal microvasculature may be an ideal surrogate marker of cerebrovascular function. This is intriguing, as the cerebral vasculature cannot be directly measured in a non-invasive manner. In epidemiological studies abnormal retinal Arteriovenous Ratios (AVR) are associated with an increased risk of stroke and cerebrovascular disease. However, the association between retinal vasoreactivity measurements and cerebral blood vessel function remains unknown. An attenuated retinal vasoreactivity may indicate endothelial dysfunction in the eye and brain and may prove to be useful as a marker of cerebrovascular disease in high risk populations such as in diabetics. STUDY GOALS: To examine 1) the impact of diabetes at different disease stages on measures of cerebrovascular function and 2) the relationship between retinal blood vessel reactivity, retinal AVRs and measures of cerebral small vessel function. METHODS: This cohort study included 29 type 2 diabetics, 14 pre-diabetics, and 14 healthy controls (ages: 37 to 75 years). Retinal vasoreactivity was measured with the Dynamic Vessel Analyzer (Imedos, Jena, Germany) following high frequency flicker light stimulation. Cerebrovascular blood flow velocity of the Middle Cerebral Artery (MCA) was assessed by Transcranial Doppler Ultrasound (TCD) (Siemens, USA). RESULTS: Progression of diabetes was found to be significantly associated with attenuation of light flicker stimulus response (P=0.0009 artery, P=0.0001 vein, CI 95%), AVR (P=0.0070, CI 95%), PI (P=0.0202, CI 95%), RI (P=0.0033, CI 95%) and hyperventilation-breath hold (P≤0.0001, CI 95%). Across all groups, attenuated retinal arterial and venous diameter responses to the light flicker stimulus were associated with an increase in MCA RI (P=0.02, r=-0.30 artery, P=0.06, r=-0.24 vein, CI 95%). An attenuated venous diameter response was associated with an increase in PI (P=0.02, r=-0.29 vein, CI 95%). In addition, attenuated retinal diameter responses were also associated with a decrease in MCA mean flow velocities following hyperventilation-breath hold (P=0.05, r=0.26 artery, P=0.01, r=0.34 vein, CI 95%). Attenuated retinal responses were also correlated with a reduction in AVR (P=0.05, r=0.26 artery, P=0.15, r=0.19 vein, CI 95%). CONCLUSION: Impairment of retinal vasoreactivity is associated with cerebrovascular dysfunction across the continuum of diabetes, possibly indicating that the eye reflects changes in cerebral blood vessel function and stroke risk.


Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Tu Mai ◽  
Andre' Diedrich ◽  
Pandu Gangula ◽  
Emily Garland ◽  
David Robertson

Calcitonin gene related peptide (CGRP) is known to be a potent microvascular dilator and hypotensive agent. This peptide and its receptors are distributed widely in both central and peripheral nervous systems. CGRP-containing neural fibers are closely associated with blood vessels in the arterial circulation where its release leads to vascular dilation. However, its role in cardiovascular regulation remains controversial. We studied the hemodynamic and autonomic function, as well as blood vessel structure in CGRP knockout (KO) mice. Blood pressure (BP), heart rate (HR) and activity level were assessed at least one week after mice were implanted with telemeters. Ten CGRP KO and ten wild type (WT) mice (4-5 month old) were used in this study. After the recording period, 24-hr urine and blood were collected for assessment of catecholamines and their metabolites. To study the baroreflex sensitivity, phenylephrine and sodium nitroprusside were administered in an acute study with seven mice from each group. We found no significant difference in 24-hr mean arterial pressure (MAP) (105.0 ± 1.8mmHg, vs. 112.1 ± 3.1mmHg, p= 0.05) between the two groups. There was also no difference in HR (KO: 566.4 ± 12.1; WT: 581.9 ± 8.5, p = 0.31). Norepinephrine was greatly elevated in both plasma and 24-hr urine in KO mice (in urine: KO: 956 ± 91 pg/ml, WT: 618 ± 46pg/ml, p = 0.004; in plasma: KO: 2505 ± 596pg/ml, n=6, WT: 1168 ± 98 pg/ml, p = 0.04). Paradoxically, cardiovagal baroreflex sensitivity was higher in the KO mice (KO: 3.2 ± 0.7 ms/mmHg, n=7, WT: 1.4 ± 0.3 ms/mmHg, n=7, p=0.03). Thoracic aortas were collected from both groups to measure vessel stiffness. The diameter at 125 mmHg of the aorta was significantly smaller in CGRP KO mice than in WT (321±30μm, vs. 422±82μm, p<0.01). Therefore, we hypothesize that although CGRP may have a limited contribution to physiological cardiovascular regulation, it may play a significant role in modulating the vagal tone and the structure properties of blood vessels.


Sign in / Sign up

Export Citation Format

Share Document