U-46619 but not serotonin increases endocannabinoid content in middle cerebral artery: evidence for functional relevance

2005 ◽  
Vol 288 (6) ◽  
pp. H2694-H2701 ◽  
Author(s):  
David J. Rademacher ◽  
Sachin Patel ◽  
W.-S. Vanessa Ho ◽  
Amanda M. Savoie ◽  
Nancy J. Rusch ◽  
...  

Cerebral vascular smooth muscle cells express the CB1 cannabinoid receptor, and CB1 receptor agonists produce vasodilation of cerebral arteries. The purpose of this study was to determine whether vasoconstriction of rat middle cerebral artery (MCA) results in the local formation of endocannabinoids (eCBs), which, via activation of CB1 receptors, oppose the vasoconstriction in a feedback manner. The thromboxane A2 (TXA2) mimetic U-46619 significantly increased N-arachidonylethanolamine (AEA) and 2-arachidonylglycerol (2-AG) content of isolated MCA, whereas 5-hydroxytrypamine (5-HT) decreased AEA and 2-AG content. If eCBs play a feedback role in the regulation of MCA tone, then CB1 receptor antagonists should enhance the constriction of MCA produced by U-46619 but not 5-HT. U-46619 caused concentration-dependent constrictions of endothelium-denuded MCA. Two CB1 receptor antagonists SR-141716 and AM-251 decreased the EC50 value for U-46619 to constrict endothelium-denuded MCA without affecting the maximal effect. A low concentration of CB1 receptor agonist Win-55212-2 (30 nM) produced vasodilation of MCAs constricted with low but not saturating concentrations of U-46619. SR-141716 had no effect on the 5-HT concentration-contraction relationship. These data suggest that TXA2 receptor activation increases MCA eCB content, which, via activation of CB1 receptors, reduces the constriction produced by moderate concentrations of the TXA2 agonist. Although 5-HT-induced vasoconstriction is reduced by exogenous CB1 receptor agonist, activation of 5-HT receptors does not increase eCB content. These results suggest that MCA production of eCBs is not regulated by constriction per se but likely via a signaling pathway that is specific for TXA2 receptors and not 5-HT receptors.

1999 ◽  
Vol 276 (2) ◽  
pp. H341-H349 ◽  
Author(s):  
Gavin R. Norton ◽  
Angela J. Woodiwiss ◽  
Robert J. McGinn ◽  
Mojca Lorbar ◽  
Eugene S. Chung ◽  
...  

Presently, the physiological significance of myocardial adenosine A2a receptor stimulation is unclear. In this study, the influence of adenosine A2a receptor activation on A1 receptor-mediated antiadrenergic actions was studied using constant-flow perfused rat hearts and isolated rat ventricular myocytes. In isolated perfused hearts, the selective A2a receptor antagonists 8-(3-chlorostyryl)caffeine (CSC) and 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM-241385) potentiated adenosine-mediated decreases in isoproterenol (Iso; 10−8 M)-elicited contractile responses (+dP/d t max) in a dose-dependent manner. The effect of ZM-241385 on adenosine-induced antiadrenergic actions was abolished by the selective A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (10−7 M), but not the selective A3 receptor antagonist 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS-1191, 10−7 M). The A2a receptor agonist carboxyethylphenethyl-aminoethyl-carboxyamido-adenosine (CGS-21680) at 10−5 M attenuated the antiadrenergic effect of the selective A1 receptor agonist 2-chloro- N 6-cyclopentyladenosine (CCPA), whereas CSC did not influence the antiadrenergic action of this agonist. In isolated ventricular myocytes, CSC potentiated the inhibitory action of adenosine on Iso (2 × 10−7 M)-elicited increases in intracellular Ca2+concentration ([Ca2+]i) transients but did not influence Iso-induced changes in [Ca2+]itransients in the absence of exogenous adenosine. These results indicate that adenosine A2areceptor antagonists enhance A1-receptor-induced antiadrenergic responses and that A2a receptor agonists attenuate (albeit to a modest degree) the antiadrenergic actions of A1 receptor activation. In conclusion, the data in this study support the notion that an important physiological role of A2a receptors in the normal mammalian myocardium is to reduce A1 receptor-mediated antiadrenergic actions.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zhihua Xu ◽  
Zhenhua Tong ◽  
Yang Duan ◽  
Dengxiang Xing ◽  
Hongyan Song ◽  
...  

Objective: To explore the relation between diffusion-weighted and susceptibility weighted imaging (DWI-SWI) mismatch and collateral circulation or prognosis in patients with occluded M1 segments of middle cerebral artery (MCA).Methods: We enrolled 59 patients with MCA M1-segment occlusion for a retrospective review of baseline clinical and imaging data. As markers of circulatory collaterals, prominent laterality of posterior (PLPCA) and anterior (PLACA) cerebral arteries on magnetic resonance angiography (MRA) studies and a hyperintense vessel sign (HVS) on T2 fluid-attenuated inversion recovery (FLAIR) images were collectively scored. The extent of acute cerebral infarction was then quantified on DWI, using the Alberta Stroke Program Early CT Score (DWI-ASPECTS). Hypointensity vessel sign prominence (PVS) was also evaluated by SWI and similarly scored (SWI-ASPECT) to calculate DWI-SWI mismatch [(DWI-ASPECTS) – (SWI-ASPECTS)], ranging from −10 to 10 points.Results: DWI-SWI mismatch showed significant associations with PLPCA, PLACA, HVS prominence, and collective collateral scores (all, p < 0.05). National Institutes of Health Stroke Scale (NIHSS), DWI-SWI mismatch, and DWI-ASPECTS also differed significantly according to patient prognosis (good vs. poor) after MCA M1-segment occlusion (p < 0.05). In binary logistic regression analyses, NIHSS and DWI-SWI mismatch emerged as independent prognostic factors (p < 0.05).Conclusions: Collateral circulation may be an important aspect of DWI-SWI mismatch, which in this study correlated with prognostic outcomes of MCA M1-segment occlusion.


2020 ◽  
pp. 028418512094671 ◽  
Author(s):  
Dong Hyuk Shin ◽  
Sang Kuk Han ◽  
Jang Hee Lee ◽  
Pil Cho Choi ◽  
Sang O Park ◽  
...  

Background A hyper-intense vessel sign on fluid attenuated inversion recovery magnetic resonance imaging (FHV) represents slow blood flow in the cerebral arteries. Purpose To investigate the relationship between the proximal FHV (pFHV) on initial magnetic resonance imaging (MRI) and the status of the culprit vessel (stenosis, obstruction) in hyper-acute strokes affecting the territory of the middle cerebral artery (MCA). Material and Methods The study participants consisted of 105 patients presenting to the emergency department (ED) with acute MCA infarction within 4.5 h of onset of symptoms. Patients underwent brain MRI within 45 min of arrival at the ED and angiography within 2 h of arrival. Culprit vessel status and presence of a pFHV on initial MRI were investigated retrospectively. Results The pFHV was observed in 71/105 (67.6%) patients who presented with a hyper-acute MCA infarction. All patients with hyper-acute MCA infarction caused by internal carotid artery (90.6% caused by M1 occlusion, 92.9% caused by M2 occlusion) showed a pFHV on initial MRI. After logistic regression analysis, the presence of a pFHV showed significant positive correlation with large vessel occlusion (adjusted odds ratio [OR] 34.533, 95% confidence interval [CI] 9.781–121.926; P < 0.001). A pFHV was not associated with severe large vessel stenosis. Conclusion A pFHV is independently representative of the acute occlusion of intervention-eligible proximal arteries within the territory of the MCA. If a patient with a hyper-acute MCA infarction shows a pFHV, aggressive flow augmentation strategies and early activation of intervention team should be warranted for best patient outcome.


2003 ◽  
Vol 9 (1_suppl) ◽  
pp. 129-132
Author(s):  
T. Yamanome ◽  
M. Sasoh ◽  
Y. Kubo ◽  
Y. Nishikawa ◽  
H. Endoh ◽  
...  

For the treatment of 11 patients with hyperacute embolic occlusion of major cerebral arteries (ten with occlusion of middle cerebral artery and one with occlusion of basilar artery), TCD-enhanced thrombolysis (TCDET) was performed in combination with ultrasound irradiation, using diagnostic transcranial Doppler (TCD) (TC2-64B: 2MHz, 100mW/cm2, pulsed wave) (TCDET group), and the effectiveness of this procedure was compared with that of local intra-arterial fibrinolysis (LIF) in 45 patients with embolic occlusion of the middle cerebral artery (LIF group). Regarding dose of TPA, the LIF group used 1046.7 ± 607.8 units and the TCDET group 700.0 ± 431.3 units (p < 0.05). Regarding time technically required to attain recanalization, the LIF group required 68.2 minutes, and the TCDET group 28.6 minutes. A good outcome was noted in 60.8% of the LIF group and 64% of the TCDET group. Haemorrhagic transformation was observed in 7.8% of the LIF group and in 0% of the TCDET group. No complications due to TCD irradiation were observed in the TCDET group. These findings suggest that TCDET can be an effective method of achieving recanalization.


2000 ◽  
Vol 279 (4) ◽  
pp. R1230-R1238 ◽  
Author(s):  
Sayoko Kanie ◽  
Osamu Yokoyama ◽  
Kazuto Komatsu ◽  
Koichi Kodama ◽  
Satoshi Yotsuyanagi ◽  
...  

To evaluate the influences of γ-aminobutyric acid (GABA) mechanisms on bladder hyperactivity after left middle cerebral artery occlusion, cystometric recordings were obtained from unanesthetized female rats. Intracerebroventricular administration of both muscimol (GABAA receptor agonist; 0.1–10 nmol) and baclofen (GABAB receptor agonist; 0.1–3 nmol) produced dose-dependent inhibitions of micturition with increases in bladder capacity (BC). The effects of high doses (1–10 nmol) were similar in sham-operated (SO) and cerebral-infarcted (CI) rats. However, lower doses of muscimol (0.1 or 0.3 nmol) and baclofen (0.1 nmol) reduced BC in CI rats. After bicuculline (GABAA receptor antagonist; 1 or 3 nmol) administration, BC in both SO and CI rats first decreased and subsequently increased. An increase in urethral pressure was observed after administration of bicuculline (3 nmol) but not with either muscimol or baclofen. Infarct volumes in muscimol-, bicuculline-, or baclofen-treated rats were not significantly different from those of vehicle-treated rats. These results suggest that GABAergic mechanisms inhibit the micturition reflex at the supraspinal level but that this can change as a result of CI.


1993 ◽  
Vol 75 (6) ◽  
pp. 2805-2810 ◽  
Author(s):  
L. L. Thomsen ◽  
H. K. Iversen

A new transcranial Doppler system (3-D Transscan, Eden Medizinische Elektronik) was evaluated in relation to sex, age, intersubject, interobserver, side-to-side, and day-to-day variation. Fifty-eight healthy volunteers participated (aged 18–80 yr). Mean velocity was higher in females than in males and decreased with age. The coefficient of variation in the middle cerebral artery was 26% between subjects, 20% between sides, 16% between days, 13% between observers, and 7% during 5 min. The coefficient of variation was higher in the anterior and posterior cerebral arteries. Bruits were heard in 35 subjects, 24 females and 11 males (P = 0.002). When middle cerebral artery velocity was monitored, high- and low-frequency oscillations were found, with a mean frequency of 5 and 1.6/min, respectively. These variations underline the necessity of standardized conditions and very carefully matched control groups in studies using transcranial Doppler. This is especially important when expected changes are small and easy to overlook, as in studies of normal physiological responses and migraine.


2018 ◽  
Vol 7 (6) ◽  
pp. 308-314 ◽  
Author(s):  
Bradley A. Gross ◽  
William J. Ares ◽  
Cynthia L. Kenmuir ◽  
Ashutosh P. Jadhav ◽  
Tudor G. Jovin ◽  
...  

Introduction: Distal access catheters are an infrequent focus of technical notes in neurointervention. The 5-French SOFIA’s unique design allows for compatibility with 6-French guide catheters, while its supple construction allows for remarkably distal access for a catheter with a 0.055-inch inner diameter. Methods: The authors reviewed a prospectively maintained endovascular database for cases utilizing the 5-French SOFIA from February 2017 through November 2017. Case type, SOFIA location, microcatheter used, and catheter-related complications were noted. Results: Over the evaluated period, the 5-French SOFIA was utilized in 33 cases, including 13 aneurysm treatments, 10 arteriovenous shunt embolizations, 5 stroke thrombectomies, and 5 other cases. Of 5 flow diversion cases, 1 was for a symptomatic cavernous internal carotid artery aneurysm necessitating transradial access, another for a ruptured A3 aneurysm, and another for a middle cerebral artery (M2) aneurysm; 2 were more proximal aneurysms. Thrombectomies were for M2 (n = 3) or A2 (n = 2) occlusions. In all cases, the 5-French SOFIA reached its anticipated distal target without complication or the need to utilize a smaller/alternative catheter. Of these 33 cases, there were 10 cases of distal SOFIA target locations: 6 M2/M3, 3 anterior cerebral arteries (ACA), and 1 posterior cerebral artery (PCA). M2/M3 and PCA catheterization was achieved over 2.1-Fr microcatheters; ACA catheterization employed a 2.9-Fr microcatheter for pipeline embolization and a deployed stentriever in the setting of two thrombectomies. Conclusion: The 5-French SOFIA can be safely utilized for distal, superselective catheterization in the context of complex neurointervention, including aneurysm and arteriovenous shunt embolization and distal thrombectomy.


VASA ◽  
1999 ◽  
Vol 28 (4) ◽  
pp. 279-282 ◽  
Author(s):  
Müller ◽  
Behnke ◽  
Walter

Background: To study the pattern of cerebral blood flow velocity and cerebral resistance changes after carotid endarterectomy. Patients and methods: In 81 patients (mean age ± SD, 64 ± 8 years) with unilateral carotid endarterectomy (CEA) the systolic, diastolic and mean blood velocities, and the pulsatility index (PI) were recorded in both middle cerebral arteries preoperatively and repetitively postoperatively with the use of transcranial Doppler ultrasound (TCD). Results: In the middle cerebral artery ipsilateral to CEA mean blood velocity was increased 6 hours (64 ± 25 cm/sec; p < 0.005) and 7 days (54 ± 15 cm/sec; p < 0.05) after CEA and had returned to the preoperative level (49 ± 11 cm/sec) after 3 months. Compared to preoperatively (0.86 ±. 22), the PI was significantly increased at 6 hours examination (1.03 ±. 23, p < 0.005), and remained increased thereafter. A pathologically increased mean blood velocity (> 83 cm/sec) 6 hours after CEA occurred in 11 patients, two of them developed a slight hyperperfusion syndrome. In the contralateral middle cerebral artery, only the diastolic blood velocity showed significant changes (preoperatively, 35 ± 12 cm/sec; 3 months after CEA, 33 ± 8 cm/sec; p < 0.05). Conclusions: Using TCD, hemodynamic changes occur predominantly in the middle cerebral arteries ipsilateral to CEA. Early postoperative TCD studies may be of help to identify patients at risk to develop a hyperperfusion syndrome.


Neurosurgery ◽  
2002 ◽  
Vol 50 (5) ◽  
pp. 1026-1031 ◽  
Author(s):  
Jose G. Romano ◽  
Alejandro M. Forteza ◽  
Mauricio Concha ◽  
Sebastian Koch ◽  
Roberto C. Heros ◽  
...  

Abstract OBJECTIVE: To determine the frequency and characteristics of microembolic signals (MES) in subarachnoid hemorrhage (SAH). METHODS: Twenty-three patients with aneurysmal SAH were monitored with transcranial Doppler ultrasonography for the presence of MES and vasospasm. Each middle cerebral artery was monitored for 30 minutes three times each week. Patients were excluded if they had traumatic SAH or cardiac or arterial sources of emboli. Monitoring was initiated 6.3 days (1–16 d) after SAH and lasted 6.6 days (1–13 d). Eleven individuals without SAH or other cerebrovascular diseases who were treated in the same unit served as control subjects. Each patient underwent monitoring of both middle cerebral arteries a mean of three times; therefore, 46 vessels were studied (a total of 138 observations). Control subjects underwent assessment of each middle cerebral artery once, for a total of 22 control vessels. RESULTS: MES were detected for 16 of 23 patients (70%) and 44 of 138 patient vessels (32%) monitored, compared with 2 of 11 control subjects (18%) and 2 of 22 control vessels (9%) (P &lt; 0.05). MES were observed for 83% of patients with clinical vasospasm and 54% of those without clinical vasospasm. Ultrasonographic vasospasm was observed for 71 of 138 vessels monitored; MES were observed for 28% of vessels with vasospasm and 36% of those without vasospasm. Aneurysms proximal to the monitored artery were identified in 38 of 138 vessels, of which 34% exhibited MES, which is similar to the frequency for vessels without proximal aneurysms (31%). Coiled, clipped, and unsecured aneurysms exhibited similar frequencies of MES. CONCLUSION: MES were common in SAH, occurring in 70% of cases of SAH and one-third of all vessels monitored. Although MES were more frequent among patients with clinical vasospasm, this difference did not reach statistical significance. We were unable to demonstrate a relationship between ultrasonographic vasospasm and MES, and the presence of a proximal secured or unsecured aneurysm did not alter the chance of detection of MES. Further studies are required to determine the origin and clinical relevance of MES in SAH.


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