Cerebral Venous Thrombosis after Red Blood Cell Transfusion for the Treatment of Iron Deficiency Anemia.

A 57-year-old male presented with generalized seizure who received red blood cell (RBC) transfusion for the treatment of iron deficiency anemia (IDA). Neuroradiological findings revealed cerebral venous thrombosis (CVT) on the left frontal vein. He received anticoagulants, anticonvulsants, and iron supplements. He discharged without any neurological deficit. It should be noted that RBC transfusion might increase the risk of CVT in patients with IDA.

Cerebral Infarction After Aneurysmal Subarachnoid Hemorrhage.

Predictors for cerebral infarction, an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH), were examined. This study used data from the Prospective Registry of Subarachnoid Aneurysms Treatment (PRESAT) cohort, which included 579 patients whose ruptured aneurysms were treated with either clipping or coiling within 12 days of onset. Patient, clinical, radiographic, and treatment variables associated with cerebral infarction were determined. Ruptured aneurysms were clipped in 282 patients and coiled in 297 patients. Cerebral infarction occurred in 162 patients (28.0 %): 101 patients by cerebral vasospasm, 34 patients by clipping, and 33 patients by coiling. Univariate analyses showed that significant factors associated with cerebral infarction development were Fisher computed tomography (CT) group 3 on admission, premature aneurysm rupture during clipping procedure, cerebrospinal fluid drainage, symptomatic vasospasm, endovascular treatment for vasospasm, and shunt-dependent hydrocephalus. Multivariable logistic regression analyses showed that cerebral infarction was significantly associated with Fisher CT group 3 on admission, larger aneurysm dome size, ruptured posterior circulation aneurysms, premature aneurysm rupture during clipping procedure, symptomatic vasospasm, and infection, while endovascular treatment for vasospasm significantly decreased the development of cerebral infarction. The most important potentially treatable factor associated with cerebral infarction was symptomatic vasospasm.

Aneurysm Organization Effects of Gellan Sulfate Core Platinum Coil with Tenascin-C in a Simulated Clinical Setting and the Possible Mechanism.

BACKGROUND: This study aimed to deliver gellan sulfate core platinum coil with tenascin-C (GSCC-TNC) into rabbit side-wall aneurysms endovascularly and to evaluate the organization effects in a simulated clinical setting. METHODS: Elastase-induced rabbit side-wall aneurysms were randomly coiled via a transfemoral route like clinical settings with platinum coils (PCs), gellan sulfate core platinum coils (GSCCs), or GSCC-TNCs (n = 5, respectively). Aneurysm-occlusion status was evaluated angiographically and histologically at 2 weeks post coiling. As each rabbit coiled aneurysm provided only 2-3 tissue slices due to technical limitations and prevented immunohistochemical evaluations, a PC, GSCC, or GSCC-TNC was randomly implanted in a rat blind-ended model (n = 3, respectively) and the organization effects were immunohistochemically evaluated for expressions of tenascin-C (TNC), transforming growth factor-beta (TGF-ß), and matrix metalloproteinase-9 (MMP-9) 2 weeks later. RESULTS: Coil handling was similar among the 3 kinds of coils. GSCCs showed a significantly higher ratio of organized area to the aneurysmal cavity than PCs, but GSCC-TNCs had the greatest organization-promoting effects on aneurysms (the ratio of organized area/aneurysmal luminal area: PC, 17.9 ± 7.1%; GSCC, 54.2 ± 18.3%; GSCC-TNC, 82.5 ± 5.8%). GSCC-TNCs had intense immunoreactivities for TNC, TGF-ß, and MMP-9 in the organized thrombosis and tunica media. GSCCs also showed intense immunoreactivities for TNC, TGF-ß, and MMP-9, although the extent was less than GSCC-TNCs. The immunoreactivities were hardly found in unorganized thrombus and the tunica media of aneurysm wall in the PC group. CONCLUSIONS: This study first showed that GSCC-TNCs promote intra-aneurysmal clot organization in simulated clinical settings using rabbits possibly through the TGF-ß and MMP-9 upregulation.

Risk factors for vasospasm-induced cerebral infarct when both clipping and coiling are equally available.

INTRODUCTION: Vasospasm-induced cerebral infarct is still a significant cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: In 537 patients of the Prospective Registry of Subarachnoid Aneurysms Treatment cohort, ruptured aneurysms were treated either microsurgically or endovascularly judged by the attending neurosurgeon to be appropriate for the individual patient within 3 days of onset. Factors for vasospasm-induced cerebral infarct were examined. RESULTS: Clipping (273 patients) was preferably performed for middle cerebral artery aneurysms, while coiling (264 patients) was preferred for larger, internal carotid artery and posterior circulation aneurysms. After aneurysmal obliteration, cerebrospinal fluid drainage was performed more in clipped patients, and antithrombotic treatment was performed more in coiled patients. Vasospasm-induced cerebral infarct occurred in 17.7 %, and multivariable logistic regression showed that vasospasm-induced cerebral infarct increased the odds of poor outcome by a factor of 5.2 (adjusted odds ratio, 5.2; 95 % confidence interval, 2.8-9.8; P < 0.001). Multivariate analyses showed that vasospasm-induced cerebral infarct was significantly associated with admission World Federation of Neurosurgical Societies grade IV-V, Fisher computed tomography (CT) group 3-4, and ruptured middle cerebral artery aneurysms. CONCLUSIONS: New treatment strategies for vasospasm-induced cerebral infarct are needed, especially for ruptured middle cerebral artery aneurysm cases associated with massive SAH.

Effects of tenascin-C on early brain injury after subarachnoid hemorrhage in rats.

BACKGROUND AND PURPOSE: We previously reported that tenascin-C (TNC), a matricellular protein, was involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH), but the role of TNC in early brain injury (EBI) is unknown. This study assessed whether inhibition of TNC upregulation in brain by imatinib mesylate (imatinib), an inhibitor of the tyrosine kinases of platelet-derived growth factor receptors, prevents EBI after experimental SAH. METHODS: Rats were assigned to sham, SAH plus vehicle, and SAH plus imatinib groups (n = 4 per group). Imatinib (50 mg/kg body weight) was administered intraperitoneally to rats undergoing SAH by endovascular perforation, and EBI was evaluated using terminal deoxynucleotidyl transferase-mediated uridine 5-triphosphate-biotin nick end-labeling staining at 24 h after SAH. Imatinib-treated SAH rats were also treated by a cisternal injection of recombinant TNC. RESULTS: SAH upregulated TNC and caused EBI. Imatinib treatment suppressed both TNC upregulation and EBI at 24 h. Recombinant TNC reinduced EBI in imatinib-treated SAH rats. CONCLUSIONS: TNC may be involved in the pathogenesis of EBI after SAH.

Tenascin-C is a possible mediator between initial brain injury and vasospasm-related and -unrelated delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Tenascin-C (TNC), a matricellular protein, exerts diverse functions, including tissue remodeling and apoptosis, and is induced in cerebrospinal fluid (CSF) after aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to examine the relationships among CSF TNC levels, initial brain injury, delayed cerebral ischemia (DCI), and vasospasm after SAH. METHODS: CSF TNC levels were measured in 30 patients with aneurysmal SAH of Fisher computed tomography (CT) group III who were treated microsurgically or endovascularly with CSF drainage within 24 h of SAH. Admission World Federation of Neurosurgical Societies (WFNS) grade was supposed to indicate the severity of initial brain injury. Cerebral vasospasm was defined as narrowed (≥ 25 %) cerebral arteries demonstrated by angiography. DCI was defined as any neurological deterioration presumed related to ischemia that persisted for ≥ 1 h. RESULTS: Higher CSF TNC levels were correlated with worse admission WFNS grades. Vasospasm was aggravated with higher TNC levels. DCI occurred regardless of the degree of vasospasm but was associated with TNC induction. Multivariate analyses showed that higher TNC levels and vasospasm were independent predictors of DCI occurrence. CONCLUSIONS: SAH (initial brain injury) that is more severe induces more TNC, which may cause the subsequent development of both vasospasm and vasospasm-unrelated secondary brain injury, leading to DCI.

Vasoconstrictive effect of tenascin-C on cerebral arteries in rats.

BACKGROUND AND PURPOSE: The authors have reported that tenascin-C (TNC), a matricellular protein, is induced after subarachnoid hemorrhage (SAH), associated with cerebral vasospasm. In this study, we examined whether TNC alone causes cerebral vasospasm-like constriction of the intracranial internal carotid arteries (ICAs) in rats, focusing on the p38 mitogen-activated protein kinase (MAPK)-mediated mechanisms. METHODS: First, we injected 10 µg of TNC into the cisterna magna of healthy rats and studied morphologically whether TNC caused constriction of the left ICA at 24-72 h after administration. Second, we examined the effect of SB203580 (a p38 MAPK inhibitor) on the vessel diameter of the left ICA in healthy rats at 24 h. Third, we evaluated the effect of SB203580 on TNC-induced constriction of the left ICA in healthy rats at 24 h. RESULTS: TNC significantly induced cerebral vasospasm-like angiographic constriction of the left ICAs, which continued at least for 72 h. SB203580 itself had no effect on the diameter of normal ICAs, but abolished the TNC-induced vasoconstrictive effect on the left ICA. CONCLUSION: These findings show that TNC causes left ICA constriction via activation of p38 MAPK, resembling post-SAH vasospasm, and suggest the possible involvement of TNC in the pathogenesis of cerebral vasospasm.

Cerebral Venous Sinus Thrombosis Associated With Subclinical Hypothyroidism: A Case Report and Literature Review.

Thyroid dysfunction is a well-known cause of cerebral venous sinus thrombosis (CVST), but most reports have focused on CVST associated with hyperthyroidism, with only a few mentioning CVST associated with hypothyroidism. Subclinical hypothyroidism, characterized by thyroid hormone levels within reference values but elevated thyroid-stimulating hormone, can also cause CVST. Here, we present a case of CVST associated with subclinical hypothyroidism. A 48-year-old man with headache, nausea, and left-sided motor weakness was admitted to our hospital, with a history of economy-class syndrome. Magnetic resonance imaging revealed occlusion of the superior sagittal sinus, right transverse sinus, and right sigmoid sinus. Digital subtraction angiography (DSA) confirmed CVST from the right common carotid artery, revealing abnormal staining of the thyroid gland. The patient was serologically in a state of subclinical hypothyroidism. Consequently, the patient was diagnosed with CVST associated with subclinical hypothyroidism. Anticoagulation therapy was initiated shortly after admission. CVST gradually resolved, and the affected sinuses were recanalized. Paraplegia improved, and the patient was discharged home 19 days after admission with a modified Rankin scale of 1. Subclinical hypothyroidism can induce CVST, underscoring the importance of screening for thyroid function in CVST patients, even without apparent thyroid dysfunction symptoms. DSA findings are valuable for diagnosing thyroid disease.

Low wall shear stress is independently associated with the rupture status of middle cerebral artery aneurysms.

BACKGROUND AND PURPOSE: We determined which hemodynamic parameter independently characterizes the rupture status of middle cerebral artery (MCA) aneurysms using computational fluid dynamics analysis. METHODS: In 106 patient-specific geometries of MCA aneurysms (43 ruptured, 63 unruptured), morphological and hemodynamic parameters were compared between the ruptured and unruptured groups. Multivariate logistic regression analysis was performed to determine parameters that independently characterized the rupture status of MCA aneurysms. RESULTS: Univariate analyses showed that the aspect ratio, wall shear stress (WSS), normalized WSS, oscillatory shear index, WSS gradient, and aneurysm-formation index were significant parameters. The size of the aneurysmal dome and the gradient oscillatory number were not significantly different between the 2 groups. With multivariate analyses, only lower WSS was significantly associated with the rupture status of MCA aneurysms. CONCLUSIONS: WSS may be the most reliable parameter characterizing the rupture status of MCA aneurysms.

High-risk plaque for carotid artery stenting evaluated with 3-dimensional T1-weighted gradient echo sequence.

BACKGROUND AND PURPOSE: Preventing cerebral embolisms is a major concern with carotid artery stenting (CAS). This study evaluated 3-dimensional T1-weighted gradient echo (3D T1GRE) sequence to predict cerebral embolism related to CAS. METHODS: We performed quantitative analyses of the characteristics of 47 carotid plaques before CAS by measuring the signal intensity ratio (SIR) and plaque volume using 3D T1GRE images. We used T1-weighted turbo field echo sequence to obtain 3D T1GRE images. We also evaluated diffusion-weighted images (DWI) of the brain before and after CAS to detect ischemic lesions (DWI lesions) from cerebral emboli. RESULTS: SIR (2.17 [interquartile range 1.50-3.07] versus 1.35 [interquartile range 1.08-1.97]; P=0.010) and plaque volume (456 mm(3) [interquartile range 256-696] versus 301 mm(3) [interquartile range 126-433]; P=0.008) were significantly higher in the group of patients positive for DWI lesions (P-group: n=26) than DWI lesion-negative patients (N-group: n=21). In multivariate logistic regression analysis, SIR (P=0.007) and plaque volume (P=0.042) were independent predictors of DWI lesions with CAS. Furthermore, SIR (rs=0.42, P=0.005) and plaque volume (rs=0.36, P=0.012) were positively correlated with the number of DWI lesions. From analysis of a receiver-operating characteristic curve, the most reliable cutoff values of SIR and plaque volume to predict DWI lesions related to CAS were 1.80 and 373 mm(3), respectively. CONCLUSIONS: Quantitative evaluation of carotid plaques using 3D T1GRE images may be useful in predicting cerebral embolism related to CAS.

Tenascin-C induces prolonged constriction of cerebral arteries in rats.

Tenascin-C (TNC), a matricellular protein, is induced in association with cerebral vasospasm after subarachnoid hemorrhage. The aim of this study was to assess the vasoconstrictive effects of TNC and its mechanisms of action on cerebral arteries in vivo. Two dosages (1 and 10µg) of TNC were administered intracisternally to healthy rats, and the effects were evaluated by neurobehavioral tests and India-ink angiography at 24, 48, and 72h after the administration. Western blotting and immunohistochemistry were performed to explore the underlying mechanisms on constricted cerebral arteries after 24h. The effects of toll-like receptor 4 (TLR4) antagonists (LPS-RS), c-Jun N-terminal kinase (JNK), and p38 inhibitors (SP600125 and SB203580) on TNC-induced vasoconstriction were evaluated at 24h. Higher dosages of TNC induced more severe cerebral arterial constriction, which continued for more than 72h. TNC administration also upregulated TLR4, and activated JNK and p38 in the smooth muscle cell layer of the constricted cerebral artery. LPS-RS blocked TNC-induced TLR4 upregulation, JNK and p38 activation, and vasoconstrictive effects. SP600125 and SB203580 abolished TNC-induced TLR4 upregulation and vasoconstrictive effects. TNC may cause prolonged cerebral arterial constriction via TLR4 and activation of JNK and p38, which may upregulate TLR4. These findings suggest that TNC causes cerebral vasospasm and provides a novel therapeutic approach against it.

Effect of aneurysm treatment modalities on cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: It is still controversial if the selection of treatment modality (clip or coil) affects cerebral vasospasm development following aneurysmal subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: We enrolled 579 SAH patients in the Prospective Registry of Subarachnoid Aneurysms Treatment project, and these patients were treated either microsurgically or endovascularly within 12 days of onset. The incidence of vasospasm was compared between patients treated with clipping and coiling. RESULTS: Clipping (282 patients) was preferably performed for small aneurysms with a wide neck or middle cerebral artery aneurysms and was followed by cerebrospinal fluid drainage; coiling (297 patients) was preferred for older patients, larger, internal carotid artery and posterior circulation aneurysms, or treatment during a nonacute stage and more frequently followed by antithrombotic treatment. Univariate analyses showed that vasospasm-induced cerebral infarct occurred more frequently in clipped patients than in coiled patients, but this difference disappeared after multivariate analyses. Higher incidence of vasospasm-induced cerebral infarct after clipping was explained by the fact that clipping was selected more for the ruptured middle cerebral artery aneurysm with massive SAH or hematoma, in which vasospasm more frequently occurred. CONCLUSIONS: Treatment modalities (clip or coil) may not significantly affect the incidence of vasospasm.

Matricellular protein: a new player in cerebral vasospasm following subarachnoid hemorrhage.

INTRODUCTION: Matricellular protein (MCP) is a class of nonstructural and secreted extracellular matrix proteins that exert diverse functions, but its role in vascular smooth muscle contraction has not been investigated. MATERIAL AND METHODS: First, rat subarachnoid hemorrhage (SAH) models were produced by endovascular perforation and examined for tenascin-C (TNC) and osteopontin (OPN) induction (representatives of MCPs) in vasospastic cerebral arteries using immunostaining. Second, recombinant TNC (r-TNC), recombinant OPN (r-OPN), or both were injected into a cisterna magna in healthy rats, and the effects on the diameter of basilar arteries were determined using India ink angiography. RESULTS: In SAH rats, TNC immunoreactivity was markedly induced in the smooth muscle cell layers of spastic cerebral arteries on day 1 but not in control animals. The TNC immunoreactivity decreased on day 3 as vasospasm improved: OPN immunoreactivity, on the other hand, was more induced in the arterial wall on day 3. r-TNC injections caused prolonged contractions of rat basilar arteries, which were reversed by r-OPN, although r-OPN itself had no effect on the vessel diameter. CONCLUSIONS: MCPs, including TNC and OPN, may contribute to the pathophysiology of cerebral vasospasm and provide a novel therapeutic approach against it.

Role of platelet-derived growth factor in cerebral vasospasm after subarachnoid hemorrhage in rats.

BACKGROUND AND PURPOSE: The role of platelet-derived growth factor (PDGF) remains unknown in cerebral vasospasm after subarachnoid hemorrhage (SAH). In this study, we examined the effects of PDGF receptor (PDGFR) inactivation on cerebral vasospasm in the endovascular perforation model of SAH in rats. METHODS: Rats were assigned to sham, SAH plus vehicle, and SAH plus imatinib mesylate (imatinib) groups (n = 4 per group). Imatinib (50 mg/kg body weight), an inhibitor of the tyrosine kinases of PDGFR, or vehicle was administered intraperitoneally 30 min post-SAH. Vasospasm was evaluated in the left (perforation-sided) internal carotid artery by means of neurobehavioral tests, India ink angiography, and immunohistochemistry at 24 h after SAH. RESULTS: Imatinib significantly inhibited post-SAH PDGFR activation in the left internal carotid artery, in which vasospasm was significantly prevented. Animal's neurobehavior also showed a tendency to improve by imatinib treatment. CONCLUSIONS: PDGF may play an important role in the pathogenesis of vasospasm after SAH.

Traumatic middle meningeal arteriovenous fistula presenting with long delayed-onset facial nerve palsy without temporal bone fracture: illustrative case.

BACKGROUND: Traumatic facial nerve palsy (FNP) without temporal bone fracture (TBF) has a delayed onset in some cases; however, long delayed-onset FNP in this setting has not been reported. The middle meningeal vein (MMV) is one of the venous drainage routes from the facial nerve. Herein, the authors describe a rare case of traumatic middle meningeal arteriovenous fistula (MMAVF) presenting with the long delayed-onset FNP without TBF. OBSERVATIONS: A 42-year-old man with pulsatile tinnitus and left FNP was admitted to our hospital 4 weeks after head trauma without TBF. Cerebral angiography revealed an MMAVF between the middle meningeal artery and the MMV on the left side. Seven days after admission, the FNP showed slight improvement, and preoperative angiography revealed decreased shunt flow of the MMAVF. Transarterial coil embolization was successfully performed. Postoperative angiography showed no residual fistula. Two weeks after the procedure, there was complete resolution of the FNP. This clinical course was correlated with the angiographic findings, suggesting that the long delayed-onset FNP was caused by the traumatic MMAVF without TBF. LESSONS: In patients presenting with long delayed-onset FNP after head trauma without TBF, the vascular lesion must be evaluated to exclude MMAVF.

Imatinib mesylate prevents cerebral vasospasm after subarachnoid hemorrhage via inhibiting tenascin-C expression in rats.

Platelet-derived growth factor (PDGF) has been implicated in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH), but the mechanism remains unknown. The purpose of this study was to assess whether imatinib mesylate (imatinib), an inhibitor of the tyrosine kinases of PDGF receptors (PDGFRs), prevents cerebral vasospasm after SAH in rats, and to elucidate if tenascin-C (TNC), a matricellular protein, is involved in the mechanism. Imatinib (10 or 50 mg/kg body weight) was administered intraperitoneally to rats undergoing SAH by endovascular perforation, and the effects were evaluated by neurobehavioral tests and India-ink angiography at 24-72 h post-SAH. Western blotting and immunohistochemistry were performed to explore the underlying mechanisms in cerebral arteries at 24h post-SAH. Recombinant TNC was administered intracisternally to imatinib-treated SAH rats, and the effects were evaluated by neurobehavioral tests, India-ink angiography and immunohistochemistry at 24 h post-SAH. Both dosages of imatinib significantly prevented post-SAH neurological impairments and vasospasm at 24-72 h. SAH caused PDGFR-ß upregulation, PDGFR activation, mitogen-activated protein kinase activation, and TNC upregulation in the spastic cerebral arteries, all of which were significantly suppressed by imatinib treatment. Recombinant TNC reversed the anti-vasospastic effects and protein expression changes by imatinib. This study suggests that imatinib prevents cerebral vasospasm at least partly via inhibiting the upregulation of TNC, implying that TNC may be a new therapeutic target for post-SAH vasospasm.

Factors predicting retreatment and residual aneurysms at 1 year after endovascular coiling for ruptured cerebral aneurysms: Prospective Registry of Subarachnoid Aneurysms Treatment (PRESAT) in Japan.

INTRODUCTION: Endovascular treatment of cerebral aneurysms includes follow-up imaging to identify aneurysms that may need retreatment. The aim of this study was to determine predictors of incomplete aneurysm occlusion at 1 year after endovascular coiling for ruptured cerebral aneurysms. METHODS: In 129 patients of the Prospective Registry of Subarachnoid Aneurysms Treatment cohort, ruptured aneurysms were coiled within 14 days of onset and both initial post-coiling and 1-year follow-up digital subtraction angiography or magnetic resonance angiography were obtained. Factors predicting 1-year incomplete aneurysm occlusion (retreatment within 1-year or residual aneurysms at 1 year) were determined using multivariate logistic regression analyses. RESULTS: One-year incomplete aneurysm occlusion was identified in 59 patients, including ten patients who were retreated within 1-year post-coiling. Dome size ≥7.5 mm (P = 0.007, odds ratio (OR) = 5.00, 95% confidence interval (CI) = 1.55-16.15), pre-treatment aneurysm re-rupture (P = 0.023, OR = 3.50, 95% CI = 1.19-10.31), non-small size/small neck aneurysm (dome size, ≥10 mm or neck size, ≥4 mm; P = 0.022, OR = 3.26, 95% CI = 1.19-8.96), and residual aneurysms on immediate post-coiling angiograms (P = 0.017, OR = 1.43, 95% CI = 1.07-1.93) significantly predicted incomplete aneurysm occlusion at 1-year post-coiling. CONCLUSIONS: In addition to the characteristics of aneurysm and initially incomplete aneurysm occlusion, this study showed pre-treatment aneurysm re-rupture to be a predictor that favors closer imaging follow-ups for coiled aneurysms.

Historical perspective of carotid artery stenting in Japan: analysis of 8,092 cases in The Japanese CAS survey.

BACKGROUND AND PURPOSE: We conducted a large retrospective survey of the clinical results of carotid artery stenting (CAS) for about 10 years performed by neurointerventionists at 43 Japanese institutions. Hence, the historical perspective of CAS in Japan was demonstrated. METHODS: Cases were stratified into three separate periods based on the approval status of devices: the first period, in which off-label CAS was performed using balloon protection; the second period, using a limited number of approved devices under filter protection; the third period, using appropriate protection selected from several different options based on the preoperative evaluation (tailored CAS). Clinical results were retrospectively evaluated. Then 30-day results of each period were examined. The major adverse event (MAE) was defined as stroke, myocardial infarction or death. RESULTS: Between January 2001 and December 2010, a total of 8,092 cases were registered, including 4,072, 1,526 and 2,494 in the first, second and third period, respectively. In the first period, 92 % of CAS was performed under balloon protection. In contrast, 91 % was done under filter protection in the second period. In the third period, various protection methods were used, including balloon (31 %), filter (50 %) and proximal protection (18 %). The rate of MAE at 30 days was 6.1 %, 10.2 % and 3.5 % in the first, second and third periods, respectively, and 6.3 % in all periods combined. The rate of MAE in the third period was significantly lower than that in the first and second periods. CONCLUSIONS: The historical paradigm of CAS in Japan was demonstrated. Due to the improvement of devices, increasing experience and appropriate selection of protection, CAS is continuing to evolve into a safer and more efficacious method of stroke prevention.

Tenascin-C enhances crosstalk signaling of integrin αvß3/PDGFR-ß complex by SRC recruitment promoting PDGF-induced proliferation and migration in smooth muscle cells.

Migration and proliferation of smooth muscle cells (SMCs) are key events during neointimal formation in pathological conditions of vessels. Tenascin-C (TNC) is upregulated in the developing neointima of lesions. We evaluated the effects of TNC on responses of SMCs against platelet-derived growth factor (PDGF) stimulation. TNC coated on substrate promoted PDGF-BB-induced proliferation and migration of rat SMC cell line A10 in BrdU incorporation and transwell assays, respectively. Immunoblotting showed that TNC substrate enhanced autophosphorylation of PDGFR-ß after PDGF-BB stimulation. Integrin αvß3 is known to be a receptor for TNC in SMCs. In immunofluorescence and immunoblot of integrin αv subunit, clustering of αv-positive focal adhesions and upregulated αv expression were observed in the cells on TNC substrate. Immunoprecipitation using anti-integrin αvß3 antibody demonstrated that PDGFR-ß and integrin αvß3 were co-precipitated and that the relative amount of PDGFR-ß after the stimulation was increased by TNC treatment. TNC also promoted phosphorylation of focal adhesion kinase (FAK) at tyrosine (Y) 397 and Y925. The phosphorylated FAK was localized at focal adhesions in immunofluorescence. Phosphorylated SRC at Y418 was also seen at focal adhesions. Immunoprecipitation with αv antibody showed increased SRC association with the integrin signaling complex in the cells on TNC after PDGF treatment. In the cells on TNC substrate, crosstalk signaling between integrin αvß3 and PDGFR-ß could be amplified by SRC and FAK recruited to focal adhesions, followed by enhanced proliferation and migration of A10 cells by PDGF-BB.

Novel dynamic four-dimensional CT angiography revealing 2-type motions of cerebral arteries.

BACKGROUND AND PURPOSE: We developed a novel dynamic 4-dimensional CT angiography to accurately evaluate dynamics in cerebral aneurysm. METHODS: Dynamic 4-dimensional CT angiography achieved high-resolution 3-dimensional imaging with temporal resolution in a beating heart using dynamic scanning data sets reconstructed with a retrospective simulated R-R interval reconstruction algorithm. RESULTS: Movie artifacts disappeared on dynamic 4-dimensional CT angiography movies of 2 kinds of stationary phantoms (titanium clips and dry bone). In the virtual pulsating aneurysm model, pulsation on the dynamic 4-dimensional CT angiography movie resembled actual movement in terms of pulsation size. In a clinical study, dynamic 4-dimensional CT angiography showed 2-type motions: pulsation and anatomic positional changes of the cerebral artery. CONCLUSIONS: This newly developed 4-dimensional visualizing technique may deliver some clues to clarify the pathophysiology of cerebral aneurysms.