Basilar Artery Diameter Research Articles

Erythropoietin prevents delayed hemodynamic dysfunction after subarachnoid hemorrhage in a randomized controlled experimental setting

IntroductionErythropoietin (EPO) was proven as a promising approach for experimental subarachnoid hemorrhage (SAH). Clinical data are, however, inconclusive so far. A detailed characterization of specific EPO effects could facilitate the design of trials. The aim of the present investigation was, therefore, to characterize these effects on prevention of delayed proximal cerebral vasospasm (CVS), impaired microcirculation and cerebral blood flow (CBF) after experimental SAH. Methods27 male Sprague–Dawley rats were randomized in 3 groups: Sham, SAH control, and SAH EPO. SAH was induced by injection of 0.2ml autologous blood into the cisterna magna on days 1 and 2. Animals of the SAH EPO group received 5000iU rh EPO α 6h after the 2nd SAH intravenously. Surviving animals were examined on day 5 by MR perfusion weighted imaging (PWI). Cerebral blood flow (CBF) and volume (CBV) were determined by PWI, proximal CVS by basilar artery (BA) diameter, and neuroprotection by hippocampal cell count (CA1–CA4). ResultsBA diameter was significantly reduced in both SAH groups, but improved significantly after EPO (Sham: 144±3μm, SAH control: 79±6μm, SAH EPO 109±4μm). The rrCBV ratio was 8.78±0.72 Sham, 5.14±1.73 SAH control, and 6.80±0.44 SAH EPO. The improvement by EPO did not reach statistical significance. RrCBF ratio was also significantly reduced in both SAH groups, but was significantly improved by EPO (Sham: 8.78±0.34, SAH control: 4.26±1.05, SAH EPO 5.85±0.46). Surviving neuronal cells were significantly reduced in SAH controls in all areas, but in SAH EPO only in CA1. ConclusionThe present data suggest that an EPO application in a timely distance to the SAH is sufficient to prevent delayed proximal CVS, but that the doses were insufficient to improve microcirculation or to be directly neuroprotective.

Basilar Artery Diameter Is an Independent Predictor of Incident Cardiovascular Events

Basilar arterial (BA) dolichoectasia is associated with cerebral small-vessel disease and stroke. However, the association between moderate dilation of the BA and cerebral small-vessel disease or subsequent cardiovascular events remains unclear. This study aims to clarify the factors related to BA diameter and to clarify whether the BA diameter is an independent predictor of cardiovascular events. The study subjects comprised 493 outpatients with atherosclerotic risk factors. BA diameter, lacunar infarct, severity of deep white matter hyperintensities, and intracranial steno-occlusive lesions were assessed with MRI and magnetic resonance angiography. Then, we prospectively evaluated the association between BA diameter and cardiovascular events. The BA diameter ranged from 1.1 to 5.2 mm, and only 0.8% of the patients had dolichoectasia. Male sex, the presence of lacunar infarcts, the severity of deep white matter hyperintensities, the fetal-type variation of the circle of Willis, and intracranial steno-occlusive lesions were independently associated with BA diameter. In the mean follow-up of 6.0 years, 91 patients developed cardiovascular events. BA diameter was independently associated with total cardiovascular events after adjusting for age, sex, and conventional risk factors (hazard ratio, 1.55 per 1 mm increase in BA diameter; P=0.009). Increased BA diameter within the normal range is related to both large-vessel disease and cerebral small-vessel disease, and it could be a new predictor of cardiovascular events.

Abstract TP212: Basilar Artery Diameter Is an Independent Predictor Of Incident Cardiovascular Disease

Background and purpose: Basilar arterial dolichoectasia, is extreme dilatation and elongation of the basilar artery (BA), is associated with intracranial bleeding, stroke mortality, and cardiovascular death. However, the association between moderate dilatation of the BA and subsequent cardiovascular events remains unclear. The study aims to clarify whether the BA diameter is an independent predictor of incident cardiovascular events. Methods: The study subjects comprised 493 outpatients aged 50 years or older with atherosclerotic risk factors, who underwent brain magnetic resonance imaging (MRI). The short axis of the BA diameter, cerebral infarcts, hemorrhagic lesions, the severity of deep white matter hyperintensities (DWMH), and intracranial steno-occlusive lesions were assessed with MRI and MR angiography. We prospectively evaluated the association between BA diameter and incident cardiovascular events such as cerebrovascular events, coronary heart events, and peripheral arterial events. The Kaplan-Meier method was used to analyze survival, and Cox regression models were used to examine prognostic variables. Results: The BA diameter ranged from 1.1 to 5.2 mm, and only 0.8% of the total patients had dolichoectasia. In the mean follow-up of 6.0 years, 91 patients developed cardiovascular events. BA diameter was independently associated with the cardiovascular events after adjusting for risk factors, stroke lesions, intracranial arterial steno-occlusion, and DWMH. Patients with large BA diameter (>2.7 mm) developed more cardiovascular events compared with those with small BA diameter (≤2.7 mm) (log-rank test; p <0.001). Among the cardiovascular events, BA diameter was most strongly associated with coronary heart events; however, it was not independently associated with cerebrovascular events. Conclusion: BA diameter is independently associated with incident cardiovascular events in high-risk patients. BA diameter could be a new predictive marker of cardiovascular events.

Effect of cervical sympathetic block on cerebral vasospasm after subarachnoid hemorrhage in rabbits

Cerebral vasospasm (CVS) is a major complication after subarachnoid hemorrhage (SAH) induced by the rupture of intracranial aneurysms. The aim of the present study was to investigate the effect and mechanism of cervical sympathetic block on cerebral vasospasm of the rabbits after SAH. After successful modeling of cervical sympathetic block, 18 healthy male white rabbits were randomly divided into three groups (n=6), ie, sham operation group (Group A), SAH group (Group B) and SAH with cervical sympathetic block group (Group C). Models of delayed CVS were established by puncturing cisterna magna twice with an injection of autologous arterial blood in Groups B and C. A sham injection of blood through cisterna magna was made in Group A. 0.5 ml saline was injected each time through a catheter for cervical sympathetic block after the first injection of blood three times a day for 3 d in Group B (bilateral alternating). 0.5 ml of 0.25% bupivacaine was injected each time through a catheter for cervical sympathetic block after the first injection of blood three times a day for 7 d in Group B. 2 ml venous blood and cerebrospinal fluid were obtained before (T1), 30 min (T2) and 7 d (T3) after the first injection of blood, respectively, and conserved in a low temperature refrigerator. Basilar artery value at T1, T2 and T3 was measured via cerebral angiography. The degree of damage to nervous system at T1 and T3 was recorded. There was no significant difference in diameter of basilar artery at T1 among three groups. The diameters of basilar artery at T2 and T3 of Groups B and C were all smaller than that in Group A, which was smaller than Group C, with a significant difference. There was no significant difference in NO and NOS in plasma and cerebrospinal fluid among three groups. The NO and NOS contents at T2 and T3 of Groups B and C were all lower than Group A; Group C was higher than Group B, with a significant difference. The nerve function at T3 of Groups B and C were all lower than Group A and that of Group C higher than Group B, with a significant difference. Cervical sympathetic block can relieve cerebral vasospasm after subarachnoid hemorrhage and increase NO content and NOS activity in plasma and cerebrospinal fluid to promote neural functional recovery.

Abstract WP414: Comparative Analysis of Clinicoradiological Factors between Asymptomatic Subjects and Stroke Patients with Vertebrobasilar Dolichoectasia in Japan

Background: Vertebrobasilar dolichoectasia (VBD) is a distinct arteriopathy known as stroke risk. We aimed to elucidate etiologic factors for developing stroke in VBD patients. Methods: A total of 10345 adults (7034 men and 3311 women) underwent healthy check-up and brain magnetic resonance (MR) studies. Seven hundred eighty-one consecutive patients (452 men and 329 women) with acute brain infarct (524 patients) or brain hemorrhage (257 patients) were recruited. We reviewed medical records and MR data in both groups. VBD was defined as the diameter of the basilar artery (BA) ≥ 4.5 mm and the diameter of the intracranial vertebral artery ≥ 4.0 mm on MR angiography. The height and lateral displacement of BA were graded according to scale of Smoker et al (AJNR 1986). Asymptomatic VBD was confirmed by neurological examination. Cardiovascular disease (CVD) risk and radiological variables were analyzed statistically in asymptomatic subjects and stroke patients with VBD. Results: One hundred thirty-four subjects (118 men and 16 women) had asymptomatic VBD. Mean age (SD) was 60.3 (11.6) years. VBD existed in 60 stroke patients (54 men and 6 women). Mean age (SD) was 65.4 (13.2) years. Prevalence of VBD was 1.3% in physical check-up adults and 7.7% in stroke patients. On univariate analysis, age and the frequency of atrial fibrillation (AF), past CVD history or chronic kidney disease (CKD) defined as proteinuria or estimated glomerular filtration rate < 60 mL/min/m 2 were significantly higher in stroke patients than in asymptomatic subjects. Other CVD risk profiles, the score of the BA height and displacement did not differ statistically between both groups. The BA diameter, the frequency of brainstem compression and the number of silent infarct lesions were increased significantly in stroke patients compared to asymptomatic subjects. Multiple logistic regression analysis showed that stroke onset was significantly associated with AF [odds ratio (OR)=1.4], CKD (OR=2.0), past CVD history (OR=1.8), silent infarcts ≥ 3 lesions (OR=2.2) and BA diameter ≥ 4.9 mm (OR=1.3). Conclusion: The present study clarified independent factors for developing stroke in VBD patients. Intensive management of these clinicoradiological factors could prevent a stroke event in VBD patients.

Abstract WP437: The Relationship Between Cholesterol And Cerebral Vasospasm In A Rat Model Of Subarachnoid Hemorrhage: A Mechanistic Role For Lipid Rafts

Objective: Rho-kinase (ROK)-mediated vascular smooth muscle (VSM) contraction plays a pivotal role in cerebral vasospasm (CV). Sphingosylphosphorylcholine (SPC), a sphingolipid, induces ROK-mediated VSM contraction, and hypercholesterolemia increases SPC-ROK-mediated VSM contraction. Lipid rafts are cholesterol-enriched membrane microdomains that influence signal transduction. In this study, we report the effect of cholesterol and lipid rafts on CV. Methods: Adult male Sprague-Dawley rats (400-500g, n=53) were fed control, 1% cholesterol or 1% cholesterol +5% β-cyclodextrin (β-CD), which depletes VSM cholesterol, diets for 8 weeks. We used a double-hemorrhage rat subarachnoid hemorrhage (SAH) model, and investigated CV of the basilar artery (BA) at Day5 using a cranial window. T-Cho levels in the internal carotid artery (ICA) were measured using Gas Chromatography. The expression of Flotillin-1, a raft marker, and Flotillin-1 mRNA in the ICA were analysed by Western blot and real-time RT-PCR, respectively. Results: The BA diameters were 358.94±32.05μm and 302.21±38.36μm in control diet (non-treated) and SAH rats, respectively (n=9/group, p<0.05 vs. non-treated). SAH-induced BA contraction was markedly reversed by intracisternal infusion of 10μM Y27632 (n=4, p<0.05), a ROK inhibitor. The BA diameter in SAH rats fed the cholesterol diet was 248.11±34.56μm (n=6, p<0.05 vs. control SAH-rats), compared with 305±25.28μm in SAH rats fed a β-CD diet (n=6, p<0.05 vs. SAH-rat fed a cholesterol diet). T-Cho levels in the ICA were significantly higher in rats fed a cholesterol diet compared with the control diet (0.82±0.24 vs. 0.49±0.09mg/g, n=5/group, p=0.028) or the β-CD diet (0.47±0.06 mg/g, n=5, p=0.016 vs. cholesterol diet). Western blot analysis and real-time RT-PCR revealed increases in Flotillin-1 and Flotillin-1 mRNA expression in the ICA from rats fed a cholesterol diet, whereas Flotillin-1 and Flotillin-1 mRNA expression were not altered in the ICA from rats fed the β-CD diet. Conclusions: These results indicate that cholesterol potentiates SAH-induced CV and are compatible with a role for lipid rafts in this process.

Vertebrobasilar dolichoectasia as a risk factor for cerebral microbleeds

Both vertebrobasilar dolichoectasia (VBD) and cerebral microbleeds (CMBs) are related with the risk of intracerebral hemorrhage. We aimed to examine the relationship between the VBD and CMB in ischaemic stroke patients. A consecutive series of 182 patients hospitalized because of ischaemic stroke or transient ischaemic attack (TIA), and who underwent gradient echo brain magnetic resonance imaging were retrospectively recruited from a prospective stroke registry. CMB locations were categorized into anterior and posterior circulation. Ectasia was defined as basilar artery (BA) diameter > 4.5 mm, and dolichosis, as either BA bifurcation above the suprasellar cistern or lateral to the margin of the clivus or dorsum sellae. Whether VBD is associated with CMB anywhere in the brain or in anterior or posterior circulation territories was analysed using binary and multinomial logistic regression models. Twenty-four subjects (13.2%) had VBD and 48 (26.4%) had CMBs. CMBs were more frequently observed in patients with VBD than without (66.7% vs. 20.3%, P < 0.001). VBD was significantly associated with CMBs in any location (crude odds ratio, 7.88; 95% confidence interval, 3.10-20.02), in the posterior circulation territory only (9.63; 2.60-34.94), and in both territories (9.25; 3.40-26.29), but not in the anterior circulation only (1.14; 0.009-11.20). These associations remained unchanged after adjusting for age, gender, hypertension, leukoaraiosis and stroke subtype. VBD in patients with ischaemic stroke or TIA is independently associated with CMBs, especially in the posterior circulation territory.

Alleviation of cerebrovascular spasm by cervical sympathetic ganglia block after subarachnoid hemorrhage in rats

Objective To investigate the role and mechanism of cervical sympathetic ganglia block in alleviation of cerebrovascular spasm (CVS) of rabbits after subarachnoid hemorrhage ( SAH ).Methods A total of 18 healthy male white rabbits whose cervical sympathetic ganglia were successfully blocked were randomly divided into three groups:sham operation group (Group A),SAH group (Group B) and SAH with cervical sympathetic ganglia block group (Group C).Venous blood (2 ml) and cerebrospinal fluid (2 ml) were obtained before the first blood injection ( T1 ),at 30 minutes after injection ( T2 ) and at day 7 after injection ( T3 ),respectively,and conserved in a low temperature refrigerator for spare use.Basilar artery value at T1,T2 and T3 was measured via cerebral angiography.The degree of damage to nervous system at T3 was recorded. Results There was no significant difference in diameter of basilar artery at T1 among three groups.At T2 and T3,the diameters of basilar artery of Groups B and C were shorter than that of Group A,with Group B shorter than Group C,with statistical differences ( P ＜0.01 ).There were no significant differences in NO and NOS in plasma and cerebrospinal fluid at T1 among three groups (P＞0.05).NO and NOS contents at T2 and T3 were lower than those at T1,with Group A lower than Groups B and C,with statistical differences (P＜0.01 ).At T3,the nerve function of Groups B and C were better than that of Group A,with Group C better than Group B ( P ＜0.01 ).Conclusion Cervical sympathetic ganglia block relieves CVS,increases NO content and NOS activity in plasma and cerebrospinal fluid and promotes neural functional recovery after SAH. Key words: Vasospasm, intracranial; Ganglia, sympathetic; Subarachnoid hemorrhage

Vertebral and/or basilar dolichoectasia in human adult cadavers

Intracranial arterial dolichoectasia is a condition in which arteries demonstrate an increase in length and diameter, with the vertebrobasilar system being the most commonly affected segment. Because the criteria for and degree of vertebrobasilar dolichoectasia are usually established on three-dimensional time-of-flight MR angiography, we presented the results of an anatomic study of vertebrobasilar dolichoectasia cadaveric specimens. Examination was carried out on the brains of human adult cadavers, routinely dissected at the Institute of Forensic Medicine. Measurement of the outer diameter and length of vertebral and/or basilar arteries was performed using the ImageJ processing program. There were 14 cases (14/216) of vertebral and/or basilar (dolicho)ectasia. Their classification into special (sub)types is made according to the basilar and/or vertebral diameter. The basilar length ranged from 32.91-59.37mm, and the basilar outer diameter ranged from 3.51-8.92mm in relation to the corresponding point of its measurement. The outer diameter of the vertebral arteries ranged from 0.67-5.91mm. The Games-Howell post hoc test additionally showed that a basilar outer diameter of grade III and IV was significantly larger than in grade II (p < 0.05). We noted a predisposition of males older than 40 years to arterial dolichoectasia in the vertebrobasilar system, independently from population group, as well as its asymptomatic appearance, independently from the presence of atherosclerotic plaques.

Perivascular blood induces substantial constrictions of isolated basilar artery, which can be reversed by high pCO2

The vasoconstrictor mechanisms in acute intracerebral hemorrhage have not been fully clarified. We hypothesized that perivascular hemolysed blood (HB) has substantial effects on the tone and vasomotor responses of isolated cerebral arteries.Basilar artery (BA) from male rats was isolated and placed in a pressure‐myograph chamber. The diameters of vessels were measured by videomicroscopy. After administration of HB the vasomotor function of vessels was studied in responses to acetylcholine (Ach), sodium‐nitroprusside (SNP), nifedipine (Nife) and CO2, which were obtained in control condition, in the presence of HB, and after washout of HB.The active diameters of BA were 277±11 μm. HB reduced the basal diameters of BA (to 164±11 μm; 59±4% of AD). After washing out of HB, the active diameters of BA reached the control level: 284±9 μm. In control, Ach, SNP, Nife and CO2 elicited substantial dilations in cerebral arteries (20±2%, 26±2%, 32±3% and 26±2%). In contrast, HB decreased the dilation to ACh, SNP, but not to nifedipin and CO2 (7±1%, 12±2%, 28±3% and 30±2%). After washout of HB NO‐dependent dilations were significantly reduced compared to control (ACh: 6±1%, SNP:14±2%).Findings of the present study show that extraluminal HB elicits substantial constrictions and inhibits NO‐dependent dilations, but does not affect Ca‐channel blocker and CO2‐induced dilations.

Abstract 2961: Basilar Artery Diameter Is Associated With The Severity Of Cerebral Small-vessel Disease In Patients With Vascular Risk Factors

Background and purpose: Basilar arterial dolichoectasia (extreme enlargement and elongation) has been reported to be associated with cerebral small-vessel disease (CSVD) in stroke patients. The association of moderate dilatation of the basilar artery (BA) and CSVD or cerebrovascular risk factors is not clear. We analyzed BA diameter, stroke and white matter lesions, and other clinical factors in patients with atherosclerotic risk factors. Methods: The study subjects were 411 outpatients aged 50 or over who underwent brain magnetic resonance imaging (MRI) for clinical purposes. All patients had 1 or more atherosclerotic risk factors. The minor axis of the BA diameter was measured on the axial view of the T2-weighted MRI at midpons level. The location and size of the symptomatic and asymptomatic stroke lesions were evaluated. The severity of the deep white matter lesions were also assessed with Schelten’s score system by MRI. The anatomic variation in the posterior circle of Willis was assessed by MR angiography. Results: The diameter of BA was &lt; 2.0 mm in 71 patients, 2.0 - 2.9 mm in 212 patients, 3.0 - 3.9 mm in 115 patients, 4.0 - 4.5 mm in 11 patients, and &gt; 4.5 mm in 2 patients. In the univariate analysis, age, male gender, hypertension, low HDL cholesterol, the history of ischemic heart diseases, the presence of stroke lesions, and severity of deep white matter lesions were associated with BA diameter. Patients with infarctions ≤ 15 mm had larger size of BA than those with infarctions &gt; 15 mm and those without infarctions. Patients with a bilateral adult-type posterior cerebral artery (PCA) had larger BA diameter than those with other types of PCA. In the multivariate regression analysis, male gender (P = 0.0002), the presence of stroke lesions (P = 0.009), severity of deep white matter lesions (P &lt; 0.0001), and the variation in the posterior circle of Willis (P &lt; 0.0001) were independently associated with BA diameter. Conclusion: BA diameter is associated with the severity of CSVD in high-risk patients. Dilatation process of BA and the development of CSVD may have common causes.

Experimental study on treatment of cerebral vasospasm by intracisternal infusion of NC - PLGA microspheres

Objective To study the therapeutic effects of intracisternal infusion of( nicardipine,NC) NC - PLGA microspheres solution on rabbits cerebral vasospasm (CVS) models.Method The primary SAH rabbit models were produced by injecting blood two times through cisterna magna.The CVS rabbit models were treated by intracisternal infusing of NC - PLGA microspheres and Nicardipine solution.The basal arteriospasm was observed with transcranial Doppler.The diameter of basilar artery was measured by cerebral angiography to evaluate the severity of CVS( P ＜ 0.01 ).The pathological changes of basilar artery walls were examined.Results Intracisternal infusion of NC - PLGA microspheres and Nicardipine could reduce the severity of CVS.And they could reduce the obvious morphological changes in the artierial wall of BA.Compared with intracisternal infusion of Nicardipine,using 25％ dose of intracisternal infusion of NC - PLGA microspheres could get the same effect.Conclusions The intracisternal infusion of NC - PLGA microspheres could reverse the severity of CVS and reverse the pathologic changement in the arterial wall.The therapeutic course is simple and complication rate is reduced.The technique with polymer should guide the therapy of cerebral vascular disease to some extent. Key words: Nicardipine; Intracisternal infusion; Vasospasm, intracranial

The effect of common carotid artery occlusion on delayed brain tissue damage in the rat double subarachnoid hemorrhage model

Delayed ischemic brain tissue damage in the time course of cerebral vasospasm in the rat double-subarachnoid hemorrhage (SAH) model has been described before. However, in order to enhance hemodynamic insufficiency during cerebral vasospasm (CVS), we performed-in a modification to the standard double-hemorrhage model-an additional unilateral common carotid artery occlusion (CCAO), expecting aggravation of brain-tissue damage in areas particularly sensitive to hypoxia. CVS was induced by injection of 0.25 ml autologous blood twice in the cisterna magna of Sprague-Dawley rats with and without unilateral CCAO. The animals were examined on days 2, 3, 4 and 5, and compared with the sham-operated control group without SAH. The functional deficits were graded between 0 and 3. Perfusion weighted imaging (PWI) at 3 Tesla magnetic resonance (MR) tomography was performed to assess cerebral blood flow (CBF). The brains were fixed, stained and evaluated for histological changes. On day 5, the neurological state was significantly worse in rats with SAH. The relative CBF/muscle blood ratio was significantly decreased by SAH and lowest in rats with CCAO and SAH (4.5 ± 1.1 vs 2.7 ± 0.6) compared with sham (7.9 ± 1.5; p < 0.001). Basilar artery (BA) diameter was 79 ± 5 μm (SAH) vs 147 ± 4 μm (sham, p < 0.001). Neuronal cell count in the hippocampal areas CA1-CA4 was significantly reduced by SAH on day 5 (p < 0.001) and lowest in rats with SAH and CCAO. CCAO leads to an aggravation of CVS-related delayed brain tissue damage in the modified rat double-SAH model.

Continuous intrathecal glyceryl trinitrate prevents delayed cerebral vasospasm in the single-SAH rabbit model in vivo

Delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is a major cause of high morbidity and mortality. The reduced availability of nitric oxide (NO) in blood and cerebrospinal fluid (CSF) is well established as a key mechanism of vasospasm. Systemic administration of glyceryl trinitrate (GTN), an NO donor also known as nitroglycerin, has failed to be established in clinical settings to prevent vasospasm because of its adverse effects, particularly hypotension. The purpose of this study was to analyze the effect of intrathecally administered GTN on vasospasm after experimental SAH in the rabbit basilar artery. A single-hemorrhage model of SAH in rabbits was used to induce vasospasm. GTN (0.5 mg/ml) or saline was infused via a subcutaneous implanted osmotic pump with continuous drug release into the cerebellomedullary cistern over 5 days. The degree of vasospasm in the basilar artery was recorded with angiography on day 5 after SAH and was compared to baseline angiography on day 0. Significant reduction of basilar artery diameter was observed in the SAH group with saline infusion compared to sham-operated animals. Intrathecally administered GTN had no effect on the vessel diameter in sham-operated animals, whereas it significantly prevented vasospasm in the SAH group. Intrathecal GTN infusion did not affect arterial blood pressure. Prophylactic, continuous intrathecal administration of GTN prevents vasospasm of the basilar artery in the rabbit SAH model. No toxic effects could be demonstrated in this study. The clinical safety and feasibility of this strategy need to be further investigated.

Preliminary report: Effect of cobaltous ion on cerebral vasospasm in a rabbit subarachnoid hemorrhage model

Experimental studies have suggested what the primary role is of free radical products in the development of vasospasm. It has been suggested that the degradation products of hemolysis trigger free radical reactions leading to lipid peroxidation is subarachnoid hemorrhage (SAH). Therefore, Fe2+, a degradation product of hemoglobin, seems to be the most important substance in the pathogenesis of vasospasm. Cobaltous ion was shown to be a powerful inhibitor of lipid peroxidation in biological membrane. Eleven rabbits were anesthetized and received 5 ml of autologous arterial blood into the cisterna magna. Group 1 (n=6) received 0.1 mg/kg cobalt solution intratecally via the cisterna magna simultaneously with blood. Group 2 (n =5) underwent sham operation as a control group. Forty-eight hours later the rabbits were deeply anesthetized and the brainstem was quickly removed and put under the operating microscope to measure the basilar artery diameter. Afterwards, the upper part of the brainstem was used for lipid peroxidation measurement and the lower part for the histopathological examination. Significant vasospasm was observed in four and moderate vasospasm in one rabbit of group 2; mild vasospasm was seen in five rabbits and moderate vasospasm was seen in one rabbit of group 1. There was no vasospasm in the control group. A statistically significant increase in the levels of lipid peroxide was found in the brainstem of group 2. These data demonstrate that cobaltous ion represents a promising therapeutic tool in vasospasm after SAH.

HEMOLYSED BLOOD‐INDUCED VASOMOTOR DYSFUNTION IN ISOLATED RAT CEREBRAL ARTERIES

The underlying vasoconstrictor mechanisms following hemorrhagic stroke have not yet been elucidated. We hypothesized that hemolysed blood induces vasomotor dysfunction in isolated cerebral arteries. The basilar artery (BA) from male rats were isolated, cannulated and placed in a pressure‐myograph organ chamber. The diameters of vessels were measured by videomicroscopy in the presence of physiological intraluminal pressure (80 mmHg) without intraluminal flow. The vasomotor function of the vessels was studied in response to hemolysed blood (HB). Dilatory function of vessels were obtained in control conditions, in the presence of HB and after washout of HB. The basal diameter of BA was 264±7,5 μm, whereas the passive diameter was 404±10 μm, indicating that a substantial myogenic tone developed. HB reduced the basal diameter of BA (to 204±13 μm, 77±4% of AD). After washing out of HB, the diameter of BA was 284±9 μm. In control ACh, SNP and nifedipine elicited substantial dilations (16±2%, 23±3% and 31±2%) of cerebral arteries. In contrast, in the presence of HB dilations to ACh, SNP and nifedipine (12±2%, 16±2%, 21±2%) were significantly decreased. In conclusion, the present findings suggest that hemolysed blood increases the myogenic tone and inhibits both endothelium‐dependent and ‐independent dilator mechanisms of cerebral arteries.

Therapeutic potential of peroxisome proliferator-activated receptor gamma agonist rosiglitazone in cerebral vasospasm after a rat experimental subarachnoid hemorrhage model

The pathogenesis of cerebral vasospasm is closely associated with inflammation and immune response in arterial walls. Recently, the authors proved the key role of Toll-like receptor (TLR)4 in the development of vasospasm in experimental subarachnoid hemorrhage (SAH) model. Because peroxisome proliferator-activated receptor (PPAR) gamma agonists are identified as effective inhibitors of TLR4 activation, we investigated the anti-inflammation properties of PPAR-gamma agonist rosiglitazone in basilar arteries in a rat experimental SAH model and evaluated the effects of rosiglitazone on vasospasm. Inflammatory responses in basilar arteries were assessed by immunohistochemical staining for intercellular molecule (ICAM)-1 and myeloperoxidase (MPO). Expression of TLR4 was determined by western blot analysis. The degree of cerebral vasospasm was evaluated by measuring the mean diameter and cross-sectional area of basilar arteries. Rosiglitazone suppressed the SAH-induced inflammatory responses in basilar arteries by inhibiting the TLR4 signalling. Furthermore, rosiglitazone could attenuate cerebral vasospasm following SAH. Therefore, we suggested that PPAR-gamma agonists may be potential therapeutic agents for cerebral vasospasm.

Hypercholesterolemia increases vasospasm resulting from basilar artery subarachnoid hemorrhage in rabbits which is attenuated by Vitamin E

Background:Aneurysm rupture results in subarachnoid hemorrhage (SAH) with subsequent vasospasm in the cerebral and cerebellar major arteries. In recent years, there has been increasing evidence that hypercholesterolemia plays a role in the pathology of SAH. It is known that hypercholesterolemia is one of the major risk factors for the development of atherosclerosis. Among the factors that have been found to retard the development of atherosclerosis is the intake of a sufficient amount of Vitamin E. An inverse association between serum Vitamin E and coronary heart disease mortality has been demonstrated in epidemiologic studies. Therefore, we tested, in an established model of enhanced cholesterol feed in rabbits, the effects of hypercholesterolemia on vasospasm after SAH by using computed tomography (CT) angiograms of the rabbit basilar artery; in addition, we tested the effects of Vitamin E on these conditions, which have not been studied up to now.Methods:In this study rabbits were divided into 3 major groups: control, cholesterol fed, and cholesterol + Vitamin E fed. Hypercholesterolemia was induced by a 2% cholesterol-containing diet. Three rabbit groups were fed rabbit diet; one group was fed a diet that also contained 2% cholesterol and another group was fed a diet containing 2% cholesterol and they received i.m. injections of 50 mg/kg of Vitamin E. After 8 weeks, SAH was induced by the double-hemorrhage method and distilled water was injected into cisterna magna. Blood was taken to measure serum cholesterol and Vitamin E levels. Basilar artery samples were taken for microscopic examination. CT angiography and measurement of basilar artery diameter were performed at days 0 and 3 after SAH.Results:Two percent cholesterol diet supplementation for 8 weeks resulted in a significant increase in serum cholesterol levels. Light microscopic analysis of basilar artery of hypercholesterolemic rabbits showed disturbances in the subendothelial and medial layers, degeneration of elastic fibers in the medial layer from endothelial cell desquamation, and a reduction of waves in the endothelial layer. However, the cholesterol + Vitamin E group did not exhibit these changes. The mean diameter of the basilar artery after SAH induction in the cholesterol-treated group was decreased 47% compared with the mean diameter of the control group. This value was less affected in cholesterol + Vitamin E-treated rabbits, which decreased 18% compared with the mean diameter of the control group.Conclusions:Hypercholesterolemia-related changes in the basilar artery aggravate vasospasm after SAH. Adding Vitamin E to cholesterol-treated rabbits decreased the degree of vasospasm following SAH in the rabbit basilar artery SAH model. We suggest that Vitamin E supplements and a low cholesterol diet may potentially diminish SAH complicated by vasospasm in high-risk patients.

Basilar Artery Diameter Is a Potential Screening Tool for Fabry Disease in Young Stroke Patients

Background: Fabry disease (FD) is a rare hereditary lysosomal storage disease that has been highlighted as a possible etiology of stroke at a young age. Enlarged basilar artery diameters (BADs) have been demonstrated in FD, and we hypothesize that they might be useful for the screening of FD in young stroke patients. The aim of this study was to compare BADs of young stroke patients without FD to those of FD patients and of healthy age-matched controls. Methods: BADs were measured using MR angiography in 3 age- and gender-matched groups: 25 FD patients (aged 36.5 ± 11.0 years), 26 non-FD stroke patients and 20 healthy controls. Results: Compared to the non-FD stroke patients, FD patients had significantly enlarged BADs. FD patients could be significantly separated from stroke patients by BADs (area under the curve = 0.89, 95% confidence interval 0.81–0.98). Eighty-six percent of all subjects could be correctly classified by BADs (sensitivity 84%, specificity 88.5%). Conclusions: Enlarged BADs were able to detect FD within a cohort of FD, stroke patients and healthy controls. BAD measurement could be an easily obtainable and sensitive screening tool for FD in young stroke patients.

Progressive aneurysm development following hemodynamic insult

Hemodynamic insult has been speculated to be a key factor in intracranial aneurysm formation; however, it is unclear whether a sustained insult is necessary. The authors examined whether aneurysmal degradation would continue despite the normalization of wall shear stress (WSS) by adaptive outward vascular remodeling. Twenty-five rabbits underwent either sham operation (5 animals) or bilateral common carotid artery ligation (20 animals) to augment basilar artery (BA) flow. Basilar termini (BTs) were harvested at 5 days and 3, 12, and 27 weeks postoperation. Histological changes at the BTs were quantified using an aneurysm development score (ADS) wherein the luminal length of the vessel wall exhibiting internal elastic lamina (IEL) loss, media thinning (> 30% media loss), and bulging was multiplied by the percentage of media thinning divided by the BA diameter. This score and its component variables were evaluated over the specified time points and compared with the WSS time course obtained from multiple angiography and BA flow velocity measurements. Serial examination of histological sections from the ligation group (17 rabbits survived the procedure) demonstrated localized, progressive, degenerative, and aneurysmal changes at the BTs. Prominent IEL loss was observed in BT specimens from all ligated animals. Media thinning and luminal bulging significantly progressed over the 27-week follow-up. The composite ADS significantly increased over the study period, indicating progressive aneurysm development, although the WSS returned to preligation baseline values within 5 weeks of ligation. Hemodynamic insult can elicit a pathological vascular response leading to a self-sustaining aneurysmal remodeling that does not require persistence of the original inciting factor to continue its pathological progression.