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.

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.

[Clinical presentations of Ross syndrome have changed in their lateralities following the anteriotemporal lobectomy for refractory focal epilepsy].

We describe a 60-year-old woman with medically refractory left mesial temporal lobe epilepsy accompanied by Ross syndrome. The patient had a partial triad of Ross syndrome with hypohydrosis only on her right side (contralateral to the epileptic seizure focus), Adie's tonic pupil on the right, and areflexia while her seizures used to be medically refractory. However, her hypohidrosis and Adie's tonic pupil have completely changed in terms of laterality following nearly complete seizure freedom resutling from left temporal lobectomy. This unique change in laterality in Ross syndrome is most likely caused by remote effects of the near-absent epileptic acitivity, and it also may contribute to understanding the pathophysiological mechanism of Ross syndrome.

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.

A Staged Therapy for Internal Carotid Artery Dissection Caused by Vascular Eagle Syndrome.

BACKGROUND: Eagle syndrome with stroke onset is a rare condition. Carotid stenting of dissected arteries and/or surgical resection of the elongated styloid process are frequently performed; however, there are no definitive criteria for selecting these treatments. CASE DESCRIPTION: A 46-year-old man presented with left hemiplegia. Acute infarction in the right frontal and parietal lobes and bilateral internal carotid artery (ICA) dissection due to the elongated styloid process were diagnosed via magnetic resonance imaging and computed tomography angiography. He was treated with stenting of the left ICA dissection, with observation of the right ICA dissection. However, the right ICA dissection deteriorated 4 days after the initial event, and additional stenting was performed. He underwent bilateral prophylactic styloidectomy with an extraoral approach 8 months after symptom onset. At >3 years after the styloidectomy, he has not experienced recurrence of the infarction. CONCLUSIONS: Stenting in the acute phase prevented the recurrence of stroke, and styloid process resection in the chronic phase cured vascular Eagle syndrome. This staged therapy could be beneficial in the treatment of vascular Eagle syndrome.

Staged Endovascular Treatment of Ruptured Vertebral Artery Dissection Involving the Posterior Inferior Cerebellar Artery.

In the treatment of vertebral artery (VA) dissection involving the origin of the posterior inferior cerebellar artery (PICA), the prevention of rebleeding and the preservation of VA and PICA patency are challenging. We report a case with ruptured VA dissection involving the origin of the PICA. In the acute stage, the fusiform dilatation of the dissection was first treated by means of stent-assisted coil embolization. Dual-antiplatelet therapy was administered just before stent placement. Seven days after the first treatment, two additional stents without coils were added. Rebleeding did not occur, and the lesion was thrombosed successfully 4 days after the second treatment, with the preservation of VA and PICA patency. This staged therapy appears to be beneficial in preventing rebleeding and in preserving VA and PICA patency.

Skull Meningioma Associated with Intradural Cyst: A Case Report.

We present the first report of intraosseous meningioma accompanied by intradural cyst formation. A 76-year-old woman had previously undergone breast cancer treatment, so the preoperative diagnosis was metastatic breast cancer. This case reminds us that the possibility of meningioma should be kept in mind in patients with breast cancer, irrespective of neuroimaging findings.

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.

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.

Final Results of Cilostazol-Aspirin Therapy against Recurrent Stroke with Intracranial Artery Stenosis (CATHARSIS).

PURPOSE: To compare the effect of cilostazol plus aspirin versus aspirin alone on the progression of intracranial arterial stenosis (IAS), and to compare ischemic and hemorrhagic events in patients with symptomatic IAS, an investigator-driven, nationwide multicenter cooperative randomized controlled trial (CATHARSIS; ClinicalTrials.gov Identifier 00333164) was conducted. METHODS: 165 noncardioembolic ischemic stroke patients with >50% stenosis in the responsible intracranial artery after 2 weeks to 6 months from the onset were randomly allocated to receive either cilostazol 200 mg/day plus aspirin 100 mg/day (n = 83, CA group) or aspirin 100 mg/day alone (n = 82, A group). The primary endpoint was the progression of IAS on magnetic resonance angiography at 2 years after randomization. Secondary endpoints were any vascular events, any cause of death, serious adverse events, new silent brain infarcts, and worsening of the modified Rankin Scale score. RESULTS: Progression of IAS was observed in 9.6% of the CA group patients and in 5.6% of the A group patients, with no significant intergroup difference (p = 0.53). The incidence of the secondary endpoints tended to be lower in the CA group compared with the A group, although the differences were not significant. By using exploratory logistic regression analysis adjusted for patient background characteristics, it was shown that the risk for certain combinations of secondary endpoints was lower in the CA group than in the A group [all vascular events and silent brain infarcts: odds ratio (OR) = 0.37, p = 0.04; stroke and silent brain infarcts: OR = 0.34, p = 0.04; all vascular events, worsening of modified Rankin Scale scores and silent brain infracts: OR = 0.41, p = 0.03]. Major hemorrhage was observed in 4 patients of the CA group and in 3 of the A group. CONCLUSION: Progression of IAS during the 2-year observation period appears to be less frequent than previously reported in stroke patients on antiplatelet agents after the acute phase, which could be due to the adequate control of risk factors, and because patients with stroke within 2 weeks after the onset were excluded. The results of the CATHARSIS trial suggest a potential utility of pharmacotherapies with cilostazol plus aspirin as well as of strict control of risk factors for the management of symptomatic IAS. Larger studies with higher statistical power are required to obtain conclusive results.

Angiotensin II type 1 receptor blockers suppress neointimal hyperplasia after stent implantation in carotid arteries of hypercholesterolemic rabbits.

OBJECTIVES: The purpose of this study was to examine whether oral administration of an angiotensin II type 1 receptor blocker (ARB) inhibited in-stent neointimal hyperplasia in carotid arteries of hypercholesterolemic rabbits. METHODS: Eleven male New Zealand white rabbits were subjected to endothelial injuries of the right common carotid arteries using a balloon catheter and then received chow containing 1% cholesterol for 6 weeks. A balloon-expandable stainless steel stent was subsequently inserted at the injured sites of the arteries. After stenting, five rabbits were randomly treated with an oral ARB, candesartan cilexetil (5 mg/kg per day orally), while the remaining six rabbits acted as untreated controls. Four weeks after the implantation, the rabbits were killed, followed by collection of the arteries including the stents. After careful removal of the stents, tissue sections were prepared and analyzed by morphometric and immunohistochemical methods. RESULTS: The mean thickness of the neointima was 53.6 ± 17.0 µm in the ARB-treated group, which was significantly reduced compared to 95.9 ± 16.7 µm in the control group (P = 0.0012). Immunohistochemistry showed a decrease in accumulation of macrophages and tenascin-C expression in the arterial wall in the ARB-treated animals. DISCUSSION: This study suggested that systemic administration of an ARB suppressed neointimal hyperplasia in the carotid artery following stent implantation by the anti-inflammatory effects, although the animal cohort tested was rather small. This finding implies that ARBs may be useful and practical agents for protection against in-stent restenosis in humans, and warrants further basic and clinical studies.

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.

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.

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.

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.

Using computational fluid dynamics analysis to characterize local hemodynamic features of middle cerebral artery aneurysm rupture points.

OBJECTIVE: Although rupture of cerebral aneurysms typically occurs at the fragile wall at the apex or pole, some aneurysms rupture through the body or the neck. The purpose of this study was to clarify the association between aneurysm rupture points and hemodynamic features through the use of computational fluid dynamics (CFD) analysis. METHODS: Twelve ruptured middle cerebral artery bifurcation aneurysms were analyzed by 3-dimensional computed tomographic angiography and CFD. Rupture points were evaluated on intraoperative videos by 3 independent neurosurgeons. Wall shear stress (WSS) was calculated at the rupture point, aneurysm dome, and parent artery. Intra-aneurysmal flow patterns were evaluated with cross-sectional velocity vector planes that included the rupture points. RESULTS: The mean WSS at the rupture point (0.29 Pa) was significantly lower than that at the dome (2.27 Pa) and the parent artery (8.19 Pa) (P < .01). All rupture points were located within the area of WSS ≤ 11.2% of the WSS at the parent artery. WSS at the rupture point was correlated with the minimum WSS at the dome (r = 0.64, P < .05), but not with aneurysm size (r = 0.26) or the aspect ratio (r = 0.16). Flow patterns revealed that all rupture points were located in lower-velocity area, which was associated with complex flow patterns and/or deviating necks. CONCLUSIONS: This study highlights the relationship between the local hemodynamic features and the rupture points observed during the microsurgical clipping. CFD may determine a rupture point of aneurysms using the feature of markedly low WSS.

Valsartan prevents neointimal hyperplasia after carotid artery stenting by suppressing endothelial cell injuries.

OBJECTIVES: Restenosis or neointimal hyperplasia remains an important complication after carotid artery stenting (CAS) for carotid artery stenosis. The purpose of this study was to examine if an anti-hypertensive drug, angiotensin receptor blocker (ARB), prevents post-CAS neointimal hyperplasia during the first 1-year period after CAS, and to clarify the possible mechanisms. METHODS: Hypertension had been treated with a calcium channel blocker (CCB) and/or an ARB, valsartan, by the preference of the neurosurgeon in charge in our department. At admission to perform CAS, patients were assigned to normotensive, valsartan (hypertensive patients treated with valsartan with/without any kind of CCBs), and non-valsartan (hypertensive patients treated with any kind of CCBs without ARBs) groups. Post-CAS neointimal hyperplasia was evaluated by carotid duplex ultrasound imaging in terms of intima-media thickening (IMT), which was performed at pre-CAS and at 90, 180, 270, and 360 days post-CAS. Biomarkers of oxidative stress (8-hydroxy-2'-deoxyguanosine), inflammation (C-reactive protein, tenascin-C) and endothelial cell injury (von Willebrand factor [vWF] antigen) were measured at pre-CAS and at 1, 7, and 180 days post-CAS. RESULTS: The non-valsartan group (n  =  8) had a higher incidence of maximum in-stent IMT ≧ 1.1 mm compared with the normotensive group (n  =  6). Valsartan (n  =  9) significantly suppressed plasma vWF levels at 7 days post-CAS and decreased the incidence of maximum in-stent IMT ≧ 1.1 mm compared with the non-valsartan group, although clinical parameters were similar between the two groups. Other biomarkers were not significantly different among the three groups. CONCLUSIONS: These findings suggest that valsartan may prevent post-CAS neointimal hyperplasia possibly by suppressing endothelial cell injury.

Inflammatory biomarkers in atherosclerosis: pentraxin 3 can become a novel marker of plaque vulnerability.

Inflammation is crucially involved in the development of carotid plaques. We examined the relationship between plaque vulnerability and inflammatory biomarkers using intraoperative blood and tissue specimens. We examined 58 patients with carotid stenosis. Following carotid plaque magnetic resonance imaging, 41 patients underwent carotid artery stenting (CAS) and 17 underwent carotid endarterectomy (CEA). Blood samples were obtained from the femoral artery (systemic) and common carotid artery immediately before and after CAS (local). Seventeen resected CEA tissue samples were embedded in paraffin, and histopathological and immunohistochemical analyses for IL-6, IL-10, E-selectin, adiponectin, and pentraxin 3 (PTX3) were performed. Serum levels of IL-6, IL-1ß, IL-10, TNFα, E-selectin, VCAM-1, adiponectin, hs-CRP, and PTX3 were measured by multiplex bead array system and ELISA. CAS-treated patients were classified as stable plaques (n = 21) and vulnerable plaques (n = 20). The vulnerable group showed upregulation of the proinflammatory cytokines (IL-6 and TNFα), endothelial activation markers (E-selectin and VCAM-1), and inflammation markers (hs-CRP and PTX3) and downregulation of the anti-inflammatory markers (adiponectin and IL-10). PTX3 levels in both systemic and intracarotid samples before and after CAS were higher in the vulnerable group than in the stable group. Immunohistochemical analysis demonstrated that IL-6 was localized to inflammatory cells in the vulnerable plaques, and PTX3 was observed in the endothelial and perivascular cells. Our findings reveal that carotid plaque vulnerability is modulated by the upregulation and downregulation of proinflammatory and anti-inflammatory factors, respectively. PTX3 may thus be a potential predictive marker of plaque vulnerability.

Gellan sulfate core platinum coil with tenascin-C promotes intra-aneurysmal organization in rats.

The aims of this study were to develop a new coil, gellan sulfate core platinum coil (GSCC), that delivers tenascin-C (TNC) to an aneurysm (GSCC-TNC) and to evaluate the effects on intra-aneurysmal organization. We performed in vitro adsorption tests of TNC to gellan sulfate (GS). GSCC-TNC was produced by immersing GSCC in TNC solution under the following conditions (TNC concentration 10, 50, or 100 µg/mL; TNC immersion time 15, 30, or 60 min) by monitoring intra-aneurysmal organization in a rat blind-ended aneurysm model. In addition, 20 rats randomly underwent implantation of a platinum coil or the GSCC-TNC produced under optimum conditions into an aneurysm, whose organization effects were compared in a blind fashion at 2 weeks post-surgery. GS demonstrated a high affinity to TNC in a dose-dependent fashion (affinity constant = 1.79 × 10(10) (M(-1))). GSCC immersed in 10 µg/mL of TNC solution for 30 and 60 min induced similar and better organization of aneurysmal cavity compared with that for 15 min (the ratio of the organized areas in an aneurysmal cavity-15 min, 27.2 ± 11.8 %; 30 min, 75.6 ± 11.9 %; 60 min, 82.6 ± 19.7 %, respectively) with the preservation of the aneurysmal wall structure, while higher TNC concentrations caused the destruction of the aneurysmal wall. GSCC-TNC produced under 10 µg/mL of TNC solution for 30 min showed a significantly better organization of aneurysms compared with bare platinum coils in rats. A newly developed coil, GSCC-TNC, may be effective for improving intra-aneurysmal organization after coil embolization.

Tenascin-C causes neuronal apoptosis after subarachnoid hemorrhage in rats.

The role of tenascin-C (TNC), a matricellular protein, in brain injury is unknown. The aim of this study was to examine if TNC causes neuronal apoptosis after subarachnoid hemorrhage (SAH), a deadly cerebrovascular disorder, using imatinib mesylate (a selective inhibitor of platelet-derived growth factor receptor [PDGFR] that is reported to suppress TNC induction) and recombinant TNC. SAH by endovascular perforation caused caspase-dependent neuronal apoptosis in the cerebral cortex irrespective of cerebral vasospasm development at 24 and 72 h post-SAH, associated with PDGFR activation, mitogen-activated protein kinases (MAPKs) activation, and TNC induction in rats. PDGFR inactivation by an intraperitoneal injection of imatinib mesylate prevented neuronal apoptosis, as well as MAPKs activation and TNC induction in the cerebral cortex at 24 h. A cisternal injection of recombinant TNC reactivated MAPKs and abolished anti-apoptotic effects of imatinib mesylate. The TNC injection also induced TNC itself in SAH brain, which may internally augment neuronal apoptosis after SAH. These findings suggest that TNC upregulation by PDGFR activation causes neuronal apoptosis via MAPK activation, and that the positive feedback mechanisms may exist to augment neuronal apoptosis after SAH. TNC-induced neuronal apoptosis would be a new target to improve outcome after SAH.