scholarly journals Hyperlipidemia Disrupts Cerebrovascular Reflexes and Worsens Ischemic Perfusion Defect

2013 ◽  
Vol 33 (6) ◽  
pp. 954-962 ◽  
Author(s):  
Cenk Ayata ◽  
Hwa Kyoung Shin ◽  
Ergin Dileköz ◽  
Dmitriy N Atochin ◽  
Satoshi Kashiwagi ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Apolipoprotein E ◽  
Knockout Mice ◽  
Perfusion Defect ◽  
Laser Speckle ◽  
Wild Type ◽  
Apolipoprotein E Knockout Mice ◽  
The Impact ◽  
Cerebrovascular Reflexes

Hyperlipidemia is a highly prevalent risk factor for coronary and cervical atherosclerosis and stroke. However, even in the absence of overt atherosclerosis, hyperlipidemia disrupts endothelial and smooth muscle function. We investigated the impact of hyperlipidemia on resting-brain perfusion, fundamental cerebrovascular reflexes, and dynamic perfusion defect during acute focal ischemia in hyperlipidemic apolipoprotein E knockout mice before the development of flow-limiting atherosclerotic stenoses. Despite elevated blood pressures, absolute resting cerebral blood flow was reduced by 20% in apolipoprotein E knockout compared with wild type when measured by [14C]-iodoamphetamine technique. Noninvasive, high spatiotemporal resolution laser speckle flow imaging revealed that the lower autoregulatory limit was elevated in apolipoprotein E knockout mice (60 vs. 40 mm Hg), and cortical hyperemic responses to hypercapnia and functional activation were attenuated by 30% and 64%, respectively. Distal middle cerebral artery occlusion caused significantly larger perfusion defects and infarct volumes in apolipoprotein E knockout compared with wild type. Cerebrovascular dysfunction showed a direct relationship to the duration of high-fat diet. These data suggest that hyperlipidemia disrupts cerebral blood flow regulation and diminishes collateral perfusion in acute stroke in the absence of hemodynamically significant atherosclerosis.

The role of adenosine in hypercarbic hyperemia: in vivo and in vitro studies in adenosine 2A receptor knockout and wild-type mice

2009 ◽  
Vol 110 (5) ◽  
pp. 981-988 ◽  
Author(s):  
Grzegorz Miekisiak ◽  
Kristen Yoo ◽  
Adam L. Sandler ◽  
Tobias B. Kulik ◽  
Jiang-Fan Chen ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Knockout Mice ◽  
Average Diameter ◽  
In Vitro Studies ◽  
Wild Type ◽  
Doppler Flowmetry ◽  
In The Wild

Object The authors tested the hypothesis that adenosine, acting through the A2A receptor, is not involved in hypercarbic hyperemia by assessing the effects of increased PaCO2 on cerebral blood flow (CBF) in vivo in wild-type and A2A receptor knockout mice. In addition, they evaluated the effect of abluminal pH changes in vitro on the diameter of isolated perfused penetrating arterioles harvested from wild-type and A2A receptor knockout mice. Methods The authors evaluated in a blinded fashion the CBF response during transient (60-second) hypercapnic (7% CO2) hypercarbia in anesthetized, ventilated C57Bl/6 wild-type and adenosine A2A receptor knockout mice. They also evaluated the hypercarbic response in the absence and presence of the nonselective and selective adenosine antagonists. Results Cerebral blood flow was measured using laser Doppler flowmetry. There were no differences between the CBF responses to hypercarbia in the wild-type and the knockout mice. Moreover, the hypercarbic hyperemia response was not affected by the adenosine receptor antagonists. The authors also tested the response to alteration in abluminal pH in isolated perfused, pressurized, penetrating arterioles (average diameter 63.3 ± 3.6 μm) harvested from wild-type (6 mice) and knockout (5 mice) animals. Arteriolar dilation in response to a decrease in abluminal pH, simulating the change in vivo during hypercarbia, was similar in wild-type (15.9 ± 2.6%) and A2A receptor knockout (17.7 ± 1.3%) mice. With abluminal application of CGS 21680 (10−6 M), an A2A receptor agonist, wild-type arterioles dilated in an expected manner (9.8 ± 0.7%), whereas A2A receptor knockout vessels had minimal response. Conclusions The results of the in vivo and in vitro studies in wild-type and A2A receptor knockout mice support the authors' hypothesis that hypercarbic vasodilation does not involve an adenosine A2A receptor–related mechanism.

Telmisartan prevents high-fat diet-induced neurovascular impairments and reduces anxiety-like behavior

2021 ◽  
pp. 0271678X2110034
Author(s):  
Gianna Huber ◽  
Mikolaj Ogrodnik ◽  
Jan Wenzel ◽  
Ines Stölting ◽  
Lukas Huber ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
High Fat Diet ◽  
Neurovascular Unit ◽  
Laser Speckle ◽  
Angiotensin Ii Receptor ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Whisker Pad ◽  
Receptor Blockers

Angiotensin II receptor blockers (telmisartan) prevent rodents from diet-induced obesity and improve their metabolic status. Hyperglycemia and obesity are associated with reduced cerebral blood flow and neurovascular uncoupling which may lead to behavioral deficits. We wanted to know whether a treatment with telmisartan prevents these changes in obesity. We put young mice on high-fat diet and simultaneously treated them with telmisartan. At the end of treatment, we performed laser speckle imaging and magnetic resonance imaging to assess the effect on neurovascular coupling and cerebral blood flow. Different behavioral tests were used to investigate cognitive function. Mice developed diet-induced obesity and after 16, not 8 weeks of high-fat diet, however, the response to whisker pad stimulation was about 30% lower in obese compared to lean mice. Simultaneous telmisartan treatment increased the response again by 10% compared to obese mice. Moreover, telmisartan treatment normalized high-fat diet-induced reduction of cerebral blood flow and prevented a diet-induced anxiety-like behavior. In addition to that, telmisartan affects cellular senescence and string vessel formation in obesity. We conclude, that telmisartan protects against neurovascular unit impairments in a diet-induced obesity setting and may play a role in preventing obesity related cognitive deficits in Alzheimer’s disease.

Sign in / Sign up

Export Citation Format

Share Document