Masahiko Tagawa

Iba1+/NG2+ macrophage-like cells expressing a variety of neuroprotective factors ameliorate ischemic damage of the brain

In a transient 90-min middle cerebral artery occlusion (MCAO) model of rats, a large ischemic lesion is formed where macrophage-like cells massively accumulate, many of which express a macrophage marker, Iba1, and an oligodendrocyte progenitor cell marker, NG2 chondroitin sulfate proteoglycan (NG2); therefore, the cells were termed BINCs (Brain Iba1+/NG2+ Cells). A bone marrow transplantation experiment using green-fluorescent protein-transgenic rats showed that BINCs were derived from bone marrow. 5-Fluorouracil (5FU) injection at 2 days post reperfusion (2 dpr) markedly reduced the number of BINCs at 7 dpr, causing enlargement of necrotic volumes and frequent death of the rats. When isolated BINCs were transplanted into 5FU-aggravated ischemic lesion, the volume of the lesion was much reduced. Quantitative real-time RT-PCR showed that BINCs expressed mRNAs encoding bFGF, BMP2, BMP4, BMP7, GDNF, HGF, IGF-1, PDGF-A, and VEGF. In particular, BINCs expressed IGF-1 mRNA at a very high level. Immunohistochemical staining showed that IGF-1-expressing BINCs were found not only in rat but also human ischemic brain lesions. These results suggest that bone marrow-derived BINCs play a beneficial role in ischemic brain lesions, at least in part, through secretion of neuroprotective factors.

Plasma thrombin-cleaved osteopontin elevation after carotid artery stenting in symptomatic ischemic stroke patients

Atherothrombosis is the primary pathophysiology that underlies ischemic cerebral infarction. Osteopontin (OPN) is produced in atherosclerotic lesions and is cleaved by activated thrombin. We hypothesized that the rupture or damage of an unstable atherosclerotic plaque increases plasma levels of thrombin-cleaved OPN (trOPN). This study included 90 patients who received carotid angioplasty with stenting (CAS), 23 patients with essential hypertension (EHT) and 10 patients who were treated with carotid endarterectomy (CEA). The CAS patient group included 36 patients that had pre- and post-operative blood tests, diffusion-weighted imaging (DWI) using cerebral MRIs and estimated thrombus debris within the protection device. Immunohistochemistry of CEA specimens revealed that trOPN was detected around intra-plaque vessels. The highest tertile of plasma trOPN levels in CAS patients was higher than trOPN levels in EHT patients. Post-operative trOPN levels were significantly higher in symptomatic compared with asymptomatic patients (P=0.003). New ipsilateral DWI-positive patients revealed higher post-operative trOPN levels (P=0.003) and a higher grade of thrombi (P<0.001) than DWI-negative patients. TrOPN may be a novel biomarker that reflects the atherothrombotic status in ischemic stroke.

Ethmoidal dural arteriovenous fistula with unusual drainage route treated by transarterial embolization

Ethmoidal dural arteriovenous fistulas (AVFs) are rare intracranial lesions associated with a high risk of intracranial hemorrhage. In particular, this entity with reflux drainage directly into the ophthalmic vein is extremely rare. We report a case of ethmoidal dural AVF with direct drainage of the superior ophthalmic vein (SOV) and inferior ophthalmic vein (IOV), successfully treated by endovascular surgery. A 58-year-old man presented with progressive diplopia. Angiography and contrast-enhanced CT showed an ethmoidal dural AVF supplied via the bilateral anterior ethmoidal arteries and venous drainage through the left SOV and IOV. A transarterial approach through the bilateral anterior ethmoidal arteries was used to place the microcatheter close to the fistula site. After intra-arterial embolization with 20% N-butyl cyanoacrylate, the dural AVF was completely occluded. In patients with good vascular access, endovascular transarterial embolization may be an effective and less invasive treatment strategy for ethmoidal dural AVF.

Plasma thrombin-cleaved osteopontin as a potential biomarker of acute atherothrombotic ischemic stroke.

We investigated whether thrombin-cleaved osteopontin N-terminal is useful as a blood biomarker of acute atherothrombotic ischemic stroke. Acute ischemic stroke patients were prospectively evaluated with brain magnetic resonance imaging and cardiac evaluations for etiological diagnosis according to the Trial of Org 10172 in Acute Stroke Treatment classification. They were divided into the atherothrombotic and non-atherothrombotic groups. Thrombin-cleaved osteopontin N-terminal, osteopontin, matrix metalloproteinase-9, S100B, C-reactive protein and D-dimer levels were measured from blood samples collected at admission. After excluding patients who met the exclusion criteria or had stroke of other/undetermined etiology, 60 of the 100 patients initially enrolled were included in the final analysis. The ischemic stroke subtypes were atherothrombotic (n=28, 46.7%), cardioembolic (n=19, 31.7%) and lacunar (n=13, 21.7%). Thrombin-cleaved osteopontin N-terminal and matrix metalloproteinase-9 levels were significantly higher in the atherothrombotic than in the non-atherothrombotic group (median (interquartile range): 5.83  (0.0–8.6 ) vs. 0.0  (0.0–3.3) pmol l−1, P=0.03 and 544   (322–749 ) vs. 343   (254–485) ng ml−1, P=0.01, respectively). After adjustment for the prevalence of hypertension, diabetes and dyslipidemia, thrombin-cleaved osteopontin N-terminal levels of >5.47 pmol l−1 (odds ratio, 16.81; 95% confidence interval, 3.53–80.10) and matrix metalloproteinase-9 levels of >605.5 ng ml−1 (6.59; 1.77–24.60) were identified as independent predictors of atherothrombosis. Within 3 h from stroke onset, only thrombin-cleaved osteopontin N-terminal independently predicted atherothrombosis and thus may add valuable, time-sensitive diagnostic information in the early evaluation of ischemic stroke, especially the atherothrombotic subtype.

Usefulness of the fusion imaging of 3D-CT and MRA for carotid artery stenting with minimum use of contrast medium in patient with renal dysfunction

Patients with severe internal carotid artery (ICA) stenosis with multiple medical problems generally undergo carotid artery stenting (CAS). However, it is difficult to perform CAS in some patients because iodinated contrast medium is hard to use. We report a patient with asymptomatic ICA stenosis and chronic renal failure, in whom successful treatment was achieved using CAS with minimal use of iodinated contrast medium. A 68-year-old man with severely chronic renal failure was consulted for treatment of left ICA stenosis. Magnetic resonance angiography (MRA) and carotid echography revealed left ICA severe stenosis, and systemic non-contrast MRA showed left femoral artery constriction, but right femoral artery to be intact. CAS was therefore performed through the right femoral artery, using non-contrast three-dimensional computed tomography (3D-CT) with MRA fusion imaging, intravascular ultrasonography, and a small amount of iodinated low-osmolar contrast medium. Postoperative course was uneventful with no aggravation of renal dysfunction, and he was discharged 7 days postoperatively. These techniques are very useful for patients with chronic renal failure, and this present case represents the first report of CAS treated by using non-contrast 3D-CT with MRA fusion image technique.

Utility of bulging technique for endovascular treatment of small and wide-necked aneurysms with a Low-profile Visualized Intraluminal Support (LVIS Jr.) device: A case report and review of the literature:

Small and broad-necked aneurysms are generally very difficult to treat using endovascular therapy. The arrival of the low-profile stent (e.g., Low-profile Visualized Intraluminal Support; LVIS) has enabled reconstructive treatment for these aneurysms. In addition, the bulging technique using LVIS is an effective and attractive technique for performing stent-assisted coiling to preserve parent arteries and achieve neck coverage. We report here a patient with a small and wide-necked ruptured basilar artery (BA) top aneurysm, in whom successful treatment was achieved by stent-assisted coiling with LVIS Jr. using the bulging technique. A 74-year-old woman with moderate hypertension consulted for treatment of subarachnoid hemorrhage with a ruptured BA top aneurysm measuring 2.7 mm in height with a 4.3 mm neck. We initially tried emergency balloon-assisted coiling, but coiling proved difficult. We therefore performed stent-assisted coiling with LVIS Jr. using the bulging technique. The postoperative course was uneventful, with no aggravation of neurological symptoms, and the patient was discharged 14 days postoperatively. This treatment strategy with LVIS Jr. using the bulging technique may be very useful for patients with a ruptured aneurysm with a small and broad neck that would otherwise require treatment with intravascular devices or open surgery.

Case Report: Ethmoidal dural arteriovenous fistula with unusual drainage route treated by transarterial embolization

Ethmoidal dural arteriovenous fistulas (AVFs) are rare intracranial lesions associated with a high risk of intracranial hemorrhage. In particular, this entity with reflux drainage directly into the ophthalmic vein is extremely rare. We report a case of ethmoidal dural AVF with direct drainage of the superior ophthalmic vein (SOV) and inferior ophthalmic vein (IOV), successfully treated by endovascular surgery. A 58-year-old man presented with progressive diplopia. Angiography and contrast-enhanced CT showed an ethmoidal dural AVF supplied via the bilateral anterior ethmoidal arteries and venous drainage through the left SOV and IOV. A transarterial approach through the bilateral anterior ethmoidal arteries was used to place the microcatheter close to the fistula site. After intra-arterial embolization with 20% N-butyl cyanoacrylate, the dural AVF was completely occluded. In patients with good vascular access, endovascular transarterial embolization may be an effective and less invasive treatment strategy for ethmoidal dural AVF.