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Background A low-profile visualized intraluminal support (LVIS) device may incompletely expand during stent deployment in tortuous vessels. However, the cause of incomplete expansion remains uninvestigated. We aimed to examine in vitro the factors causing incomplete expansion in LVIS deployment by using various vessel models. Methods A linear model group was created by connecting linear silicone tubes (inner diameter 4 mm) at both sides of the LVIS deployment vessel (inner diameter 4 mm) with different curvature angles of 10–140° at 10° intervals. For comparison, proximal and distal bending model groups were created, both with 90° bending on the proximal/distal larger curvature side of the deployment vessel. A single operator macroscopically deployed an LVIS (4.5×32 mm) four times in each model and 56 times in each group. Results In each model group the LVIS deployment vessel with a narrow curvature angle incompletely expanded. Incomplete expansion occurred significantly more frequently in the distal bending model group (34%, 19/56) compared with that in the linear model group (14.3%, 8/56; p Conclusions Factors such as acute angle, distal bending, and proximal bending of the deployment vessel can cause incomplete LVIS expansion.

Background and Purpose— The treatment and prognosis of acute large vessel occlusion with mild symptoms have not been sufficiently studied. The present study aimed to investigate the clinical or radiological predictors of clinical outcome in patients with stroke with mild symptoms due to acute large vessel occlusion. Methods— Of 2420 patients with acute large vessel occlusion in the RESCUE-Japan Registry 2 (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Registry 2), a multicenter prospective registry in Japan, patients with modified Rankin Scale scores of 0 to 2 before onset and initial National Institutes of Health Stroke Scale (NIHSS) scores of 0 to 5 were examined in post hoc analysis. We examined the clinical and radiological characteristics associated with a favorable outcome (modified Rankin Scale score, 0–2 at 90 days) using multivariate analysis, as well as the factors associated with a favorable outcome in patients treated with endovascular therapy. Results— We analyzed 272 patients (median age, 73 years; median NIHSS score on admission, 3). Eighty-six (31.6%) patients were treated with intravenous recombinant tissue-type plasminogen activator, 54 (19.9%) underwent endovascular therapy, and 208 (76.5%) showed a favorable outcome. In multivariate analysis, age P Conclusions— Younger age, lower initial NIHSS score, intravenous recombinant tissue-type plasminogen activator, and absence of hyperglycemia were independently associated with a favorable outcome in patients with acute large vessel occlusion with low NIHSS scores. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02419794.

Background Dissection of a vertebral artery (VA) fenestration is extremely rare. We herein present the first case of a patient who presented with the dissection of a VA fenestration limb accompanied by occlusion after rupture, who was treated with internal trapping of the dissected limb and the parent artery proximal to the fenestration. Case Description A 55-year-old man presented with sudden headache and altered consciousness. Computed tomography at admission showed subarachnoid hemorrhage. Angiography showed occlusion of the inner limb of the vertebrobasilar junction fenestration, and the occluded ends had a tapered shape, suggesting the occlusion of the dissection of the inner limb after rupture. Angiography immediately before embolization revealed inner limb recanalization with an irregular string sign; thus only the inner limb was embolized. Angiography after embolization showed near-complete suppression of the blood flow in the inner limb; however, a slight antegrade flow through the coil mass was observed in the late phase. The procedure was finished with the expectation of complete occlusion over time with natural heparin reversal. Angiography 8 days after embolization revealed a significant increase in antegrade blood flow through the coil mass within the inner limb. Therefore additional embolization of the parent artery proximal to the fenestration was performed, which achieved complete occlusion. Conclusions The embolization length was limited and the antegrade blood flow through the other limb remained during internal trapping for the dissected VA fenestration limb; therefore careful observation of the blood flow to the dissected segment after embolization is necessary.

Background: Ruptured intracranial fungal mycotic aneurysms have a high mortality rate. It has been reported that the number of opportunistic infections has increased. Here, we report the first case of a patient in which a ruptured fungal carotid artery aneurysm was successfully treated by stent-assisted coil embolization. Case Description: A 76-year-old male receiving dual antiplatelet therapy due to a recent percutaneous transluminal angioplasty presented with blurred vision of the right eye and diplopia. Magnetic resonance imaging revealed a fungal mass in the sphenoid sinus, and the patient was pathologically diagnosed with invasive aspergillosis. After receiving oral voriconazole for 4 weeks, he was admitted to the hospital with hemorrhagic shock from epistaxis. The right internal carotid artery angiography revealed a de novo irregularly shaped aneurysm at the cavernous portion, projecting into the sphenoid sinus, which was considered to be the source of bleeding. Due to the lack of ischemic tolerance and urgent demand for hemostasis, we performed a stent-assisted coil embolization of the aneurysm without interrupting the blood flow. Postoperatively, the patient had no neurological deficit, and treatment with voriconazole was continued for 12 months without rebleeding. Conclusion: Stent-assisted coil embolization without parent artery occlusion might be a promising option for the urgent treatment of ruptured fungal mycotic aneurysms. Long-term administration of voriconazole might be continued for 12 months for such patients.

Background: Spinal dural defects can result in superficial siderosis (SS) of the central nervous system. Closure of the defect can stop or slow the progression of the disease. Here, we evaluated, whether preoperative three-dimensional fast steady-state acquisition MR could adequately detect these defects and, thus, facilitate their closure and resolution. Case Description: A 65-year-old right-handed male presented with a 33-year history of the left C8 root avulsion and a 3-year history of slowly progressive gait difficulties and hearing loss. The T2*-weighted imaging revealed symmetrical hemosiderin deposition throughout his central nervous system. A left C6-C7 dural defect involving only inner layer was identified using a three-dimensional MR (3D-FIESTA). It was treated through a left C6-7 hemilaminectomy and successfully sealed with adipose tissue and fibrin glue. Subsequently, the progression of cerebellar ataxia was halted, nevertheless the sensorineural hearing loss worsened even over the next 2 years. Conclusion: 3D-FIESTA reconstruction was approved to be useful tool for identifying the tiny hole of the inner dural layer responsible for SS.

Background and Purpose: High blood pressure increases bleeding risk during treatment with antithrombotic medication. The association between blood pressure levels and the risk of recurrent stroke during long-term secondary stroke prevention with thienopyridines (particularly prasugrel) has not been well studied. Methods: This was a post hoc analysis of the randomized, double-blind, multicenter PRASTRO-I trial (Comparison of Prasugrel and Clopidogrel in Japanese Patients With Ischemic Stroke-I). Patients with noncardioembolic stroke were randomly assigned (1:1) to receive prasugrel 3.75 mg/day or clopidogrel 75 mg/day for 96 to 104 weeks. Risks of any ischemic or hemorrhagic stroke, combined ischemic events, and combined bleeding events were determined based on the mean level and visit-to-visit variability, including successive variation, of systolic blood pressure (SBP) throughout the observational period. These risks were also compared between quartiles of mean SBP level and successive variation of SBP. Results: A total of 3747 patients (age 62.1±8.5 years, 797 women), with a median average SBP level during the observational period of 132.5 mm Hg, were studied. All the risks of any stroke (146 events; hazard ratio, 1.318 [95% CI, 1.094–1.583] per 10-mm Hg increase), ischemic stroke (133 events, 1.219 [1.010–1.466]), hemorrhagic stroke (13 events, 3.247 [1.660–6.296]), ischemic events (142 events, 1.219 [1.020–1.466]), and bleeding events (47 events, 1.629 [1.172–2.261]) correlated with increasing mean SBP overall. Similarly, an increased risk of these events correlated with increasing successive variation of SBP (hazard ratio, 3.078 [95% CI, 2.220–4.225] per 10-mm Hg increase; 3.051 [2.179–4.262]; 3.276 [1.172–9.092]; 2.865 [2.042–4.011]; 2.764 [1.524–5.016], respectively). Event rates did not differ between the clopidogrel and prasugrel groups within each quartile of SBP or successive variation of SBP. Conclusions: Both high mean SBP level and high visit-to-visit variability in SBP were significantly associated with the risk of recurrent stroke during long-term medication with either prasugrel or clopidogrel after stroke. Control of hypertension would be important regardless of the type of antiplatelet drugs. Registration: URL: https://www.clinicaltrials.jp ; Unique identifier: JapicCTI-111582.

Background Statins have been associated with reduced recurrence and better functional outcomes in patients with acute ischemic stroke. However, the effect of statins in patients with acute large vessel occlusion (LVO) is not well scrutinized. Methods and Results RESCUE (Recovery by Endovascular Salvage for Cerebral Ultra‐Acute Embolism)‐Japan Registry 2, a physician‐initiated registry, enrolled 2420 consecutive patients with acute LVO who were admitted to 46 centers across Japan within 24 hours of onset. We compared patients with and without statin use after acute LVO onset (statin group and nonstatin group, respectively) in terms of the modified Rankin scale at 90 days. We estimated that the odds ratios for the primary outcome was modified Rankin scale and we estimated the odds ratios for a 1‐scale lower modified Rankin scale adjusting for confounders. After excluding 12 patients without LVO and 9 patients without follow‐up, the mean age of 2399 patients was 75.9 years; men accounted for 55% of patients. Statins were administered to 447 (19%) patients after acute LVO onset. Patients in the statin group had more atherothrombotic cerebral infarctions (34.2% versus 12.1%, P P P P =0.02). The mortality at 90 days was lower in the statin group (4.7%) than the nonstatin group (12.5%; P P =0.02). Conclusions Statin administration after acute LVO onset is significantly associated with better functional outcome and mortality at 90 days.

Background Although the incidence is rare, patients with moyamoya disease are at risk of stroke during pregnancy. Therefore, there is limited information regarding appropriate peripartum management. Herein, we report a case of major postpartum cerebral infarction in a patient with moyamoya disease, despite previous direct bilateral anastomosis of the superficial temporal artery to the middle cerebral artery (STA-MCA). Case description The patient was a 32-year-old woman who had undergone direct STA-MCA anastomosis and encephalo-myo-synangiosis in her childhood. This was her second pregnancy. She sustained a major ischemic stroke in the left middle cerebral artery area on postpartum day 3, which resulted in right hemiplegia and aphasia. On magnetic resonance angiography, simultaneous interruption of antegrade flow of the left middle cerebral artery and STA-MCA anastomosis was observed. The patency of these vessels was confirmed before the first pregnancy. The patient’s consciousness was impaired for several days due to edema in the infarct area. However, her condition improved following conservative treatment with osmotic diuretics and antiplatelet therapy; the patient recovered independent gait and her aphasia improved after 5 months of inpatient rehabilitation. Conclusions Careful monitoring of women with moyamoya disease is recommended during pregnancy and the peripartum period even if direct or indirect anastomosis has been previously performed.

Background Occipital sinus (OS) dural arteriovenous fistula (DAVF) is extremely rare, and we are aware of no case accompanied by cerebral hemorrhage. We present a case of OS DAVF presenting with cerebellar hemorrhage, treated successfully by transvenous embolization. Case Description A 62-year-old female presented with headache and nausea of recent onset. Computed tomography revealed left cerebellar hemorrhage with perihematomal edema. Angiography showed OS DAVF fed by bilateral occipital and posterior meningeal arteries, with drainage into the left inferior hemispheric vein and right transverse sinus receiving the shunt flow from OS. The caudal side of the OS was occluded. The inferior hemispheric vein was dilated with 2 varices, and the junction between the OS and right transverse sinus was narrowed. Because the OS was not involved in normal cerebellar drainage, transvenous embolization of the OS was performed. The microcatheter was advanced to the OS from the transverse sinus during balloon occlusion at the confluence of sinuses. Coils were placed in the OS from the caudal to cranial side, and complete occlusion of the shunt was obtained. Conclusions This is the first report of OS DAVF presenting with cerebellar hemorrhage. Transvenous embolization of the affected OS appears ideal when transvenous access is feasible, and the OS is not involved in normal venous drainage of the cerebellum.

Background Some mechanical thrombectomy techniques for acute ischemic stroke use a combination of an aspiration catheter and stent retriever. We experienced a rare case of aspiration catheter coil breakage and subsequent retrieval using a stent retriever. Case Description A 79-year-old man suddenly developed somnolence, global aphasia, and right hemiplegia. Magnetic resonance imaging revealed acute infarction of the left frontal lobe and occlusion of the left common carotid artery. Thus, using an aspiration catheter and a stent retriever, mechanical thrombectomy was performed. The stent retriever was deployed from the middle cerebral artery to the internal carotid artery and retracted into the aspiration catheter placed in the internal carotid artery proximal to the thrombus. The catheter was bent during retraction of the stent retriever. After thrombus aspiration, the internal carotid and anterior and middle cerebral arteries were successfully reperfused; however, the stent retriever captured a broken section of the winding coil of the aspiration catheter. We suspected that an X-ray marker on the stent retriever broke the winding coil at the bent segment of the aspiration catheter and the stent captured the broken coil. Conclusions The combined use of an aspiration catheter and a stent retriever may cause unexpected device breakage, especially when the catheter is bent.

Carotid stenosis may occur as a late complication following cervical radiation therapy(RT);however, it may also progress in the early post-RT period. This study aimed to characterize the clinical features associated with the early progression of post-RT carotid stenosis.We retrospectively reviewed clinical records of 30 patients who had undergone unilateral or bilateral cervical RT between January 2010 and November 2014. We analyzed the pre- and post-RT stenosis of their carotid arteries using contrast-enhanced computed tomography images. The arteries were classified as progressive or non-progressive according to the presence or absence of stenosis progression within five years after RT. Using univariate and multivariate analyses, we evaluated the following potential clinical risk factors:age;gender;history of hypertension, hyperlipidemia, diabetes mellitus, coronary artery disease, or smoking habit;antiplatelet or statin use;radiation dose;and prior presence of carotid stenosis before RT.In total, we reviewed 57 irradiated carotid arteries and identified 9 with early post-RT progression. Carotid stenosis before RT was observed in 88.9% of arteries in the progressive group but only 2% of arteries in the non-progressive group and it predicted progression(univariate and multiple logistic regression analyses, p0.0001). No other clinical characteristics had a significant association with the progression of carotid stenosis.Prior presence of carotid stenosis may be a risk factor for its early progression after RT. Pre-RT screening of cervical arteries may be useful, and strict management of carotid stenosis is critical in patients with cervical radiation therapy.

Highlights • Visual metacognition of controls was dependent on spatial frequency. • Visual metacognition of schizophrenia patients was independent of spatial frequency. • Patients and controls differently rely on the dorsolateral prefrontal cortex. • Sensory inputs may reach metacognitive circuits in an atypical manner among patients., Although altered early stages of visual processing have been reported among schizophrenia patients, how such atypical visual processing may affect higher-level cognition remains largely unknown. Here we tested the hypothesis that metacognitive performance may be atypically modulated by spatial frequency (SF) of visual stimuli among individuals with schizophrenia, given their altered magnocellular function. To study the effect of SF on metacognitive performance, we asked patients and controls to perform a visual detection task on gratings with different SFs and report confidence, and analyzed the data using the signal detection theoretic measure meta-d′. Control subjects showed better metacognitive performance after yes- (stimulus presence) than after no- (stimulus absence) responses (‘yes-response advantage’) for high SF (HSF) stimuli but not for low SF (LSF) stimuli. The patients, to the contrary, showed a ‘yes-response advantage’ not only for HSF but also for LSF stimuli, indicating atypical SF dependency of metacognition. An fMRI experiment using the same task revealed that the dorsolateral prefrontal cortex (DLPFC), known to be crucial for metacognition, shows activity mirroring the behavioral results: decoding accuracy of perceptual confidence in DLPFC was significantly higher for HSF than for LSF stimuli in controls, whereas this decoding accuracy was independent of SF in patients. Additionally, the functional connectivity of DLPFC with parietal and visual areas was modulated by SF and response type (yes/no) in a different manner between controls and patients. While individuals without schizophrenia may flexibly adapt metacognitive computations across SF ranges, patients may employ a different mechanism that is independent of SF. Because visual stimuli of low SF have been linked to predictive top-down processing, this may reflect atypical functioning in these processes in schizophrenia.

Background Endovascular therapy has been shown to be effective in patients with acute cerebral large‐vessel occlusion, but real‐world efficacies are unknown. Methods and Results We conducted a prospective registry at 46 centers between October 2014 and January 2017. Eligible patients were those who were aged 20 years or older, with acute cerebral large‐vessel occlusion, and who were hospitalized within 24 hours of the onset. We enrolled both consecutive patients who were treated with or without endovascular therapy. Endovascular therapy included thrombectomy, balloon angioplasty, stenting, local fibrinolysis, and piercing. The primary outcome was a favorable outcome as defined by a modified Rankin Scale of 0 to 2 at 90 days after onset. Secondary outcomes were modified Rankin Scale of 0 to 1 and mortality. Safety outcomes were intracerebral hemorrhage or a recurrence of ischemic stroke. We constructed the 2242 (1121 each) propensity score–matched patients cohort based on a propensity score for endovascular therapy and estimated the adjusted odds ratio, followed by sensitivity analyses on original 2399 (1278 in endovascular therapy versus 1121 in no endovascular therapy) patients. In the propensity score–matched cohort, favorable outcomes were observed in 35.3% and 30.7% of patients in the endovascular therapy and no endovascular therapy groups, respectively ( P= 0.02). The adjusted odds ratio for the favorable outcome was 1.44 (95% confidence interval, 1.10–1.86, P =0.007). The efficacy of endovascular therapy in achieving favorable outcomes did not differ between our subgroups and in the sensitivity analyses. Conclusions Endovascular therapy decreased disabilities at 90 days in real‐world patients with acute cerebral large‐vessel occlusion. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT02419794.

Molecularly targeted therapy has been adopted to treat a number of cancers. Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor, is a representative agent used in molecularly targeted therapeutic regimens. However, the therapeutic effect of bevacizumab for the treatment of brain metastases remains unknown. We report the clinical effects of low dose bevacizumab(≤2.5mg/kg/week)to treat recurrent brain metastases.We retrospectively analyzed patients with brain metastases who had been treated with bevacizumab between 2012 and 2016 at our institution. We identified clinical characteristics, including age, gender, primary tumor site, dose of bevacizumab, therapeutic and adverse effects, and magnetic resonance imaging results. The lesions were assessed with the RECIST criteria based on gadolinium-enhanced T1-weighted, T2-weighted, and FLAIR images. Statistical analysis was performed using t-test and Fisher's exact test.The cohort comprised 26 patients(8 men, 18 women)with a median age of 61 years(range 39-82 years). There were no significant clinical differences between the low dose and non-low dose groups. Patients in the low dose group did not report any adverse effects from bevacizumab. Three patients with brain metastases from colon cancer are illustrated to report the clinical course of low dose bevacizumab.Low dose bevacizumab may be a safe and effective therapeutic option to treat recurrent brain metastases from bevacizumab-sensitive cancers.

ObjectiveThe recently published arteriovenous malformation-related intracerebral haemorrhage (AVICH) score showed better outcome prediction for patients with arteriovenous malformation (AVM)-related intracerebral haemorrhage (ICH) than other AVM or ICH scores. Here we present the results of a multicentre, external validation of the AVICH score.MethodsAll participating centres (n=11) provided anonymous data on 325 patients to form the Spetzler-Martin (SM) grade, the supplemented SM (sSM) grade, the ICH score and the AVICH score. Modified Rankin score (mRS) at last follow-up (mean 25.6 months) was dichotomized into favourable (mRS 0-2, n=210) and unfavourable (mRS 3-6;n=115). Univariate and AUROC analyses were performed to validate the AVICH score.ResultsExcept nidus structure and AVM size, all single parameters forming the SM, sSM, ICH and AVICH score and the scores itself were significantly different between both outcome groups in the univariate analysis. The AVICH score was confirmed to be the highest predictive outcome score with an AUROC of 0.765 compared with 0.705 for the ICH score and 0.682 for the sSM grade.ConclusionThe multicentre-validated AVICH score predicts clinical outcome superior to pre-existing scores. We suggest the routine use of this score for future clinical outcome prediction and in clinical research.Trial registration numberNCT02920645.

Few effective treatment options exist for stroke beyond the hyperacute period. Radical generation and myeloperoxidase (MPO) have been implicated in stroke. We investigated whether pharmacologic reduction or gene deletion of this highly oxidative enzyme reduces infarct propagation and improves outcome in the transient middle cerebral artery occlusion mouse model (MCAO). Mice were treated with 4-aminobenzoic acid hydrazide (ABAH), a specific irreversible MPO inhibitor. Three treatment regimens were used: (1) daily throughout the 21-day observational period, (2) during the acute stage (first 24 hours), or (3) during the subacute stage (daily starting on day 2). We found elevated MPO activity in ipsilateral brain 3 to 21 days after ischemia. 4-Aminobenzoic acid hydrazide reduced enzyme activity by 30% to 40% and final lesion volume by 60% ( P

We report a case in which strict anticoagulant therapy management was useful for a recurrent in-stent thrombosis after carotid artery stenting (CAS). An 84-year-old man presented with cognitive decline that progressed rapidly over two months. Head magnetic resonance imaging showed an acute-stage infarct occurring frequently in the right cerebral hemisphere, and he underwent hospitalization and treatment. On neck magnetic resonance angiography (MRA), severe stenosis was found at the origin of the right internal carotid artery. Since he took aspirin, clopidogrel, and a statin after placement of an indwelling coronary stent, we treated him by adding argatroban and edaravone drip therapy to his existing medication. CAS was performed on day 15 of the hospitalization. A small in-stent thrombosis with plaque protrusion was observed on a carotid sonogram performed at the second day after CAS, and re-examination at the seventh day confirmed enlargement of the lesion and an increase in peak systolic velocity; thus, a second CAS procedure was performed on the same day. After the second CAS, oral cilostazol was added for triple antiplatelet therapy (TAPT), but as the in-stent thrombosis increased further, we started a continuous infusion of heparin with the goal of an activated partial thromboplastin time (APTT) of 50 to 65 seconds. After starting heparin, the lesion did not progress; after 14 days of continuous heparin infusion, the patient was switched to TAPT, and regression of the plaque was confirmed. This case demonstrated to us that controlled anticoagulation therapy can be an effective treatment for cases in which a thrombus recurs within a stent after CAS.

The horizontal stenting technique facilitates endovascular treatment of wide-necked bifurcation intracranial aneurysms. Previous literature shows, however, that subsequent coil embolization at initial treatment results in incomplete obliteration in many cases. The authors present two consecutive cases of wide-necked large bifurcation aneurysms to describe an additional coil embolization technique following horizontal stenting. The patients were a 53-year-old female with an unruptured internal carotid artery terminus aneurysm and a 57-year-old female with a recurrent basilar artery tip aneurysm. Both patients underwent endovascular treatment with horizontal stenting followed by coil embolization with jailed double-microcatheters. Immediate complete obliteration was achieved with no complications, and no recanalization was observed at the one-year follow-up in both cases. Coil embolization with jailed double-microcatheter technique following horizontal stenting is a safe and effective strategy for wide-necked bifurcation aneurysms.

Cerebral ischemia causes neuronal death and disruption of neural circuits in the central nervous system. Various neurological disorders caused by cerebral infarction can severely impair quality of life and are potentially fatal. Functional recovery in the chronic stage mainly depends on physical treatment and rehabilitation. We aim to establish cell therapy for cerebral ischemia using embryonic stem (ES) cells, which have self-renewing and pluripotent capacities. We previously reported that the transplanted monkey and mouse ES cell-derived neural progenitors, by stromal cell-derived inducing activity method, could survive and differentiate into various types of neurons and glial cells, and form the neuronal network in basal ganglia. In this report, we induced the differentiation of the neural progenitors from mouse ES cells using the serum-free suspension culture method and confirmed the expression of various basal ganglial neuronal markers and neurotransmitter-related markers both in vitro and in vivo, which was thought to be suitable for replacing damaged striatum after middle cerebral artery occlusion. This is the first report that used selectively induced telencephalic neural progenitors into ischemia model. Furthermore, we purified the progenitors expressing the neural progenitor marker Sox1 by fluorescence-activated cell sorting and Sox1-positive neural progenitors prevented tumor formation in ischemic brain for 2 months. We also analyzed survival and differentiation of transplanted cells and functional recovery from ischemic damage.

Bone marrow stromal cells (MSCs) are an excellent source of cells for treating a variety of central nervous system diseases. In this study, we report the efficient induction of committed neural progenitor cells from rat and human MSCs (NS-MSCs) by introduction of cells with the intracellular domain of Notch-1 followed by growth in the free-floating culture system. NS-MSCs successfully formed spheres, in which cells highly expressed the neural precursor cell markers. The commitment of spheres to neural lineage cells was confirmed by their successful differentiation into neuronal cells when exposed to a differentiation medium. To determine the therapeutic potential of NS-MSCs, cells were transplanted into the cortex and striatum in a rat model of focal cerebral ischemia. The survival, distribution, and integration of NS-MSCs in the host brain were very high, and at day 100, grafted NS-MSCs were positive for dopaminergic, glutamatergic, and γ-amino butyric acid (GABA)ergic neuronal markers. They extended long neurites for nearly 6.3 mm and many of these expressed synaptophysin. Significant behavioral recovery was also observed in limb-placing and water-maze tests. These suggest a high potential for this MSC approach in the replenishment of neural cells for stroke and for a wide range of neurodegenerative conditions that require various types of neural cells.

Enhanced matrix metalloproteinases (MMPs) can cause vasogenic edema and hemorrhagic transformation after cerebral ischemia, and affect the extent of ischemic injury. We hypothesized that the endogenous MMP inhibitors, tissue inhibitor of MMPs (TIMPs), were essential to protect against blood—brain barrier (BBB) disruption after ischemia by regulating the activities of MMPs. We confirmed the transition of MMP-2 and MMP-9, and the TIMPs family after 30 mins of middle cerebral artery occlusion, and elucidated the function of TIMP-1 and TIMP-2 in focal ischemia, using TIMP-1−/−and TIMP-2−/− mice. TIMP-1 mRNA expression was gradually increased until 24 h after reperfusion. In TIMP-1−/− mice, MMP-9 protein expression and gelatinolytic activity were significantly more augmented after cerebral ischemia than those in WT mice, and were accompanied by exacerbated BBB disruption, neuronal apoptosis, and ischemic injury. In contrast, TIMP-2 gene deletion mice exhibited no significant difference in MMP expressions and the degree of ischemic injury despite an increased Evans blue leakage. These results suggest that TIMP-1 inhibits MMP-9 activity and can play a neuroprotective role in cerebral ischemia.

Cerebral blood volume (CBV) can be measured using a C-arm flat detector angiographic system. The present report describes a case in which cerebral hyperperfusion was detected with the Neuro parenchymal blood volume (PBV) system (syngo Neuro PBV IR, Siemens Medical Solutions, Erlangen, Germany) during carotid artery stenting (CAS). An 89-year-old man was referred to our hospital for cerebral brain infarction and severe stenosis of the left carotid artery. CAS was performed, and Neuro PBV was used to measure CBV both during and after the procedure. Postoperative Neuro PBV revealed dramatically increased CBV, and a hyperperfusion state was suspected. The next day, subarachnoid hemorrhage along the sulcus of the left hemisphere was revealed on computed tomography. Strict management of blood pressure was instituted just after the detection of hyperperfusion, and the patient was ultimately discharged from the hospital without any new neurological deficits. Neuro PBV has the advantage that it can be performed in the angiography suite and does not require patient transfer to an alternate setting. Therefore, intracranial hemodynamic changes can be detected during the procedure. We conclude that the Neuro PBV system is useful for monitoring intracranial hemodynamics during endovascular procedures.

Thioredoxin (Trx) is a 12-kDa protein ubiquitously expressed in all living cells that fulfills a variety of biological functions related to cell proliferation and apoptosis. It is characterized by the highly conserved reduction/oxidation (redox)-active site sequence Trp-Cys-Gly-Pro-Cys-Lys. Trx acts as a powerful antioxidant and plays an important role in maintaining critical protein thiols in the reduced state. Moreover, it has been shown to scavenge reactive oxygen species (ROS) and to protect against oxidative stress. We have reported that Trx-1 protects against neuronal damage during focal ischemia. However, the mechanisms underlying this protective effect and the effect of Trx-1 on neuronal apoptosis during ischemia have not been fully clarified. In this study, we analyzed the effect of Trx-1 overexpression against neuronal degeneration after a short duration of transient brain ischemia. Mild focal ischemia was reported to induce neuronal death through apoptosis. We employed Fluorojade-B staining to detect neuronal degeneration. In Trx transgenic mice, a smaller number of Fluorojade-B-positive neurons were detected after ischemia-reperfusion than in wild-type mice. In addition, we detected cleaved caspase-3- and TUNEL-positive cells, which indicated caspase-dependent apoptosis. Fewer caspase-3- and TUNEL-positive neurons were detected after ischemia-reperfusion in Trx transgenic mice than in wild-type mice. Furthermore, Akt signaling was reported to play a role in neuronal survival in Trx-1 overexpressing mice. After ischemia-reperfusion, Western blot and immunohistochemical analysis indicated that phosphorylation of Akt was enhanced in Trx transgenic mice after ischemia-reperfusion. Intraventricular injection of LY294002,which is a phosphoinositide 3-kinase (PI3K), vanished the neuroprotective effect in Trx-1 transgenic mice. These results indicate that Trx-1 overexpression protects neurons from apoptosis after ischemia-reperfusion.