Simultaneous assessment of cerebral hemodynamics and contrast agent uptake in lesions with disrupted blood– brain–barrier

1999 ◽  
Vol 17 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Sabine Heiland ◽  
Thomas Benner ◽  
Jürgen Debus ◽  
Katrin Rempp ◽  
Wolfgang Reith ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Blood Brain Barrier ◽  
Cerebral Hemodynamics ◽  
Brain Barrier ◽  
Blood Brain ◽  
Simultaneous Assessment

Abstract 35: Gamma Adducin Dysfunction Leads To Cerebrovascular Distention, Blood Brain Barrier Leakage, And Cognitive Deficits In The Fawn-hooded Hypertensive Rats

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Kirby N Thomas ◽  
Shaoxun Wang ◽  
Huawei Zhang ◽  
Reese F Crumpler ◽  
Parker S Elliott ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Blood Brain Barrier ◽  
Cognitive Deficits ◽  
Cerebral Hemodynamics ◽  
Brain Barrier ◽  
Transgenic Rats ◽  
Brain Volumes ◽  
Atherosclerosis Risk In Communities ◽  
Impaired Performance ◽  
Blood Brain

We have previously identified an inactivating mutation of ADD3 in FHH rats which is associated with impaired myogenic reactivity of renal arterioles and podocyte function, and contributes to the development of CKD. We have found that SNPs in human ADD1 or ADD3 in the same region as Add3 in FHH rats are linked to reductions in brain volumes and impaired performance on cognitive tests in 4,286 elderly patients (67-90 years old) in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS), but the mechanisms of these pathologies are unclear. The present study examined cerebral hemodynamics and cognitive function in FHH versus FHH.1BN and FHH. Add3 rats that express the WT Add3 gene. The myogenic responses of the middle cerebral artery (MCA) and parenchymal arterioles (PA) were impaired in FHH rats. MCA diameter decreased by 15-20% in FHH.1BN (n = 27) and FHH. Add3 (n = 10) transgenic rats, but increased by 9 ± 3% in FHH rats (n = 15) when perfusion pressure was increased from 40 to 160 mmHg. PA diameter increased by 3.16 ± 2.79% in FHH (n = 5) rats versus a 19 ± 3% and 13 ± 2% decrease FHH. Add3 (n = 4) and FHH.1BN (n = 6), respectively, when pressure was increased from 10 to 40 mmHg. Autoregulation of surface and deep cortical blood flow was impaired in FHH rats and rose by 48 ± 3% (n = 22) and 41 ± 3% (n = 12), respectively, versus 32 ± 3% (n = 7) and 16 ± 5% (n = 6) in FHH. Add3 rats when MAP was increased from 100 to 160 mmHg. By using a fluorescent microscope to examine 60 μm brain sections, it was revealed that the outer diameters of PAs were distended in FHH in comparison to FHH.1BN and FHH. Add3 transgenic rats when systemic pressure was increased to 160 mmHg. Blood brain barrier leakage was also greater in FHH rats than in FHH.1BN and FHH. Add3 rats after acute elevations in pressure. FHH (n=16) rats took 40- 50% longer to navigate an eight-arm water maze than FHH. Add3 (n=11) and FHH.1BN (n=7) rats. These results indicate that variants that alter Add3 function promote cognitive dysfunction in FHH rats by altering cerebral hemodynamics and may play a similar role in cognitive deficits in elderly patients in the ARIC-NCS study. This study suggests that blood pressure should be strictly controlled in hypertensive patients identified with ADD3 variants to prevent dementia.

scholarly journals Two-Photon Fluorescence Microscopy Study of Cerebrovascular Dynamics in Ultrasound-Induced Blood—Brain Barrier Opening

2011 ◽  
Vol 31 (9) ◽  
pp. 1852-1862 ◽  
Author(s):  
Eunice E Cho ◽  
Jelena Drazic ◽  
Milan Ganguly ◽  
Bojana Stefanovic ◽  
Kullervo Hynynen
Keyword(s):  
Contrast Agent ◽  
Blood Brain Barrier ◽  
Microscopy Study ◽  
Brain Barrier ◽  
Intensity Change ◽  
Two Photon ◽  
Peak Intensity ◽  
Blood Brain ◽  
Two Photon Fluorescence ◽  
Bbb Opening

Blood-brain barrier (BBB) disruption can be achieved with ultrasound (US) and circulating microbubble (MB) contrast agent. Using dorsal US sonication and Definity, an MB contrast agent, responses of the cortical cerebral vasculature to BBB opening were observed with varying acoustic peak negative pressure (0.071 to 0.25 MPa) under two-photon microscope. Wistar rats with a craniotomy were sonicated with a single piezoelectric transducer following the intravenous injection of Texas Red for visualization of vasculature and leakage from BBB opening. Based on time-dependent intensity change in the extravascular area, the leakage was classified into three types: fast, sustained, and slow. Fast leakage was characterized by a rapid increase to peak intensity during sonication, but a decrease afterwards, occurring at all pressures and vessels sizes analyzed in our study. Sustained leakage was indicated by a similar, immediate increase to peak intensity but one that remained elevated for the duration of imaging, occurring at low-to-intermediate pressures. Slow leakage began 5 to 15 minutes after sonication, dominating at low pressures, and was more prevalent among smaller vessels than fast and sustained leakage. Our study showed the possibility of controlling leakage type and vessel size in US-induced BBB opening through varying acoustic pressure.

scholarly journals Transient Widespread Blood—Brain Barrier Alterations after Cerebral Photothrombosis as Revealed by Gadofluorine M-Enhanced Magnetic Resonance Imaging

2008 ◽  
Vol 29 (2) ◽  
pp. 331-341 ◽  
Author(s):  
Guido Stoll ◽  
Christoph Kleinschnitz ◽  
Sven G Meuth ◽  
Stefan Braeuninger ◽  
Chi Wang Ip ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Contrast Agent ◽  
Blood Brain Barrier ◽  
Brain Lesions ◽  
Mri Contrast Agent ◽  
Brain Barrier ◽  
Resonance Imaging ◽  
Blood Brain ◽  
Gadofluorine M

Magnetic resonance imaging (MRI) is a powerful tool to assess brain lesions, but currently available contrast agents are limited in the assessment of cellular and functional alterations. By use of the novel MRI contrast agent gadofluorine M (Gf) we report on imaging of transient and widespread changes of blood—brain barrier (BBB) properties as a consequence of focal photothrombotic brain lesions in rats. After i.v. application, Gf led to bright contrast in the lesions, but also the entire ipsilateral cortex on T1-weighted MRI. In contrast, enhancement after application of gadolinium diethylenetriamine-pentaacetic acid (Gd-DTPA), a common clinical indicator of BBB leakage was restricted to the lesions. Remote Gf enhancement was restricted in time to the first 24 h after photothrombosis and corresponded to a transient breakdown of the BBB as revealed by extravasation of the dye Evans blue. In conclusion, our study shows that Gf can visualize subtle disturbances of the BBB in three dimensions not detectable by Gd-DTPA. Upon entry into the central nervous system Gf most likely is locally trapped by interactions with extracellular matrix proteins. The unique properties of Gf hold promise as a more sensitive contrast agent for monitoring BBB disturbances in neurologic disorders, which appear more widespread than anticipated previously.

scholarly journals Brain Redox Imaging Using Blood—Brain Barrier-Permeable Nitroxide MRI Contrast Agent

2008 ◽  
Vol 28 (6) ◽  
pp. 1165-1174 ◽  
Author(s):  
Fuminori Hyodo ◽  
Kai-Hsiang Chuang ◽  
Artem G Goloshevsky ◽  
Agnieszka Sulima ◽  
Gary L Griffiths ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Contrast Agent ◽  
Contrast Agents ◽  
Brain Tissue ◽  
Blood Brain Barrier ◽  
Mri Contrast Agents ◽  
Mri Contrast Agent ◽  
Brain Barrier ◽  
Mri Contrast ◽  
Blood Brain

Reactive oxygen species (ROS) and compromised antioxidant defense may contribute to brain disorders such as stroke, amyotrophic lateral sclerosis, etc. Nitroxides are redox-sensitive paramagnetic contrast agents and antioxidants. The ability of a blood—brain barrier (BBB)-permeable nitroxide, methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (MC-P), as a magnetic resonance-imaging (MRI) contrast agent for brain tissue redox imaging was tested. MC-P relaxation in rodent brain was quantified by MRI using a fast Look-Locker T1-mapping sequence. In the cerebral cortex and thalamus, the MRI signal intensity increased up to 50% after MC-P injection, but increased only by 2.7% when a BBB-impermeable nitroxide, 3CxP (3-carboxy-2,2,5,5,5-tetramethylpyrrolidine-1-oxyl) was used. The maximum concentrations in the thalamus and cerebral cortex after MC-P injection were calculated to be 1.9±0.35 and 3.0±0.50 mmol/L, respectively. These values were consistent with the ex vivo data of brain tissue and blood concentration obtained by electron paramagnetic resonance (EPR) spectroscopy. Also, reduction rates of MC-P were significantly decreased after reperfusion following transient MCAO (middle cerebral artery occlusion), a condition associated with changes in redox status resulting from oxidative damage. These results show the use of BBB-permeable nitroxides as MRI contrast agents and antioxidants to evaluate the role of ROS in neurologic diseases.

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