Kazuhiko Suyama

Early increases in TNF-α, IL-6 and IL-1β levels following transient cerebral ischemia in gerbil brain

Abstract The effects of transient global ischemia using bilateral carotid artery occlusion on regional cytokine levels in gerbil brain were investigated using enzyme-linked immunoassay techniques. Brain concentrations of interleukin-6 (IL-6), interleukin-lβ (IL-1β), and tumor necrosis factor-α (TNF-α) were increased during the early recirculation period (

Kynurenine Pathway Enzymes in Brain: Responses to Ischemic Brain Injury Versus Systemic Immune Activation

Accumulation of l‐kynurenine and quinolinic acid (QUIN) in the brain occurs after either ischemic brain injury or after systemic administration of pokeweed mitogen. Although conversion of l‐[13C6]tryptophan to [13C6]‐QUIN has not been demonstrated in brain either from normal gerbils or from gerbils given pokeweed mitogen, direct conversion in brain tissue does occur 4 days after transient cerebral ischemia. Increased activities of enzymes distal to indoleamine‐2,3‐dioxygenase may determine whether l‐kynurenine is converted to QUIN. One day after 10 min of cerebral ischemia, the activities of kynureninase and 3‐hydroxy‐3,4‐dioxygenase were increased in the hippocampus, but local QUIN levels and the activities of the indoleamine‐2,3‐dioxygenase and kynurenine‐3‐hydroxylase were unchanged. By days 2 and 4 after ischemia, however, the activities of all of these enzymes in the hippocampus as well as QUIN levels were significantly increased. Kynurenine aminotransferase activity in the hippocampus was unchanged on days 1 and 2 after ischemia but was decreased on day 4, at a time when local kynurenic acid levels were unchanged. A putative precursor of QUIN, [13C6]anthranilic acid, was not converted to [13C6]‐QUIN in the hippocampus of either normal or 4‐day postischemic gerbils. Gerbil macrophages stimulated by endo‐toxin in vitro converted l‐[13C6]tryptophan to [13Ce]QUIN. Kinetic analysis of kynurenine‐3‐hydroxylase activity in the cerebral cortex of postischemic gerbils showed that Vmax increased, without changes in Km. Systemic administration of pokeweed mitogen increased indoleamine‐2,3‐dioxygenase and kynureninase activities in the brain without significant changes in kynurenine‐3‐hydroxylase or 3‐hydroxyanthranilate‐3,4‐dioxygenase activities. Increases in kynurenine‐3‐hydroxylase activity, in conjunction with induction of indoleamine‐2,3‐dioxygenase, kynureninase, and 3‐hydroxyanthranilate‐3,4‐dioxygenase in macro‐phage infiltrates at the site of brain injury, may explain the ability of postischemic hippocampus to convert l‐[13C6]tryptophan to [13C6]QUIN.

Usefulness of intraoperative photodynamic diagnosis using 5-aminolevulinic acid for meningiomas with cranial invasion: technical case report.

OBJECTIVE We present a case of a meningioma in which photodynamic diagnosis (PDD) using 5-aminolevulinic acid was very useful in identifying the cranial involvement. CLINICAL PRESENTATION An 83-year-old woman presented with a bony, hard, immobile bulge in her left forehead. Computed tomographic scans showed a thickening in the left frontal bone with a flat mass underneath. Magnetic resonance imaging scans revealed that enhancing lesions spread to the dura mater and subcutaneous tissue around the thickened frontal bone, reaching the upper margin of the left orbit. INTERVENTION Intraoperative PDD using 5-aminolevulinic acid indicated the optimal extent of the excision by showing clear fluorescence of affected tissues. The tumor was totally resected and diagnosed as an atypical meningioma. Histopathological examination confirmed the consistency of the extent of tumor invasion with affected lesions on PDD. CONCLUSION To the best of our knowledge, this is the first case demonstrating the efficacy of PDD using 5-aminolevulinic acid for a meningioma with cranial invasion. Additional studies are warranted, as shown in cases of malignant gliomas.

Efficacy of DynaCT Digital Angiography in the Detection of the Fistulous Point of Dural Arteriovenous Fistulas

BACKGROUND AND PURPOSE: Identifying the precise hemodynamic features, including the fistulous point, is essential for treatments of dural arteriovenous fistulas (DAVFs). This study illustrates the efficacy of DynaCT digital angiograms obtained from a 3D C-arm CT to directly visualize the location of the fistulous points in DAVFs. MATERIALS AND METHODS: This retrospective study observed 14 consecutive patients with DAVFs, which included 7 cavernous sinuses, 4 transverse-sigmoid sinuses, 2 convexity-superior sagittal sinuses, and 1 tentorial sinus. In the assessment of the practical applicability for the diagnosis of DAVFs, images obtained from 2D digital subtraction angiography (DSA) and DynaCT were comparatively evaluated. RESULTS: In all patients, DynaCT digital angiography could clearly demonstrate the feeding arteries, the fistulous points, and the draining veins. Significant anatomic landmarks for the fistulous points with relationships to osseous structures were also provided. Compared with 2D DSA, DynaCT digital angiograms demonstrated 12 additional findings in 8 patients (57%), including the detection of the fistulous points (n = 7), the feeders (n = 1), the retrograde leptomeningeal drainage (n = 1), the draining veins (n = 1), and the venous anomaly (n = 2). CONCLUSIONS: In comparison with 2D DSA, DynaCT may provide more detailed information to evaluate DAVFs. DynaCT digital angiograms have a high contrast and isotropic spatial resolution, allowing a reliable visualization of small vessels and fine osseous structures. Such detailed information, especially for the location of the fistulous points, could be very useful for either the endovascular or the surgical treatments of DAVFs.

Anoxic depolarization determines ischemic brain injury

To clarify the role of anoxic depolarization (AD) in ischemic brain injury, we examined the correlation between AD and ischemia-induced neuronal injury. Twenty-eight rats underwent transient forebrain ischemia with lowering of blood pressure and bilateral carotid occlusion while direct current shifts, electrocorticogram, and cortical blood flow (CoBF) were epidurally recorded from the right parietal cortex. One week later the right parietal cortex was studied histopathologically. AD appeared 0.5-3.0 min after carotid occlusion in 21 of 28 animals. Circulation was reinitiated 15 min after AD onset in 11 rats (group A) and 10 min after onset in 10 rats (group B). AD did not develop during 20 min of ischemia in 7 rats (group C). All 12 rats (6 from group A and 6 from group B) in which CoBF decreased below 9.5% of control flow exhibited AD. Histopathologic examination disclosed massive neuronal necrosis in 5 of the 6 group A animals with marked flow reduction but in none from group B. CoBF fell between 9.5% and 20% in 14 rats, among these, AD appeared in 9 (5 from group A and 4 from group B) but not in 5 (group C). Massive neuronal necrosis was demonstrated in 3 of 5 rats from group A. Ischemic neuronal changes were absent or minimal in only 1/5 of group A animals, a much lower fraction than in group B (4/4, p < 0.05) or in group C (5/5, p < 0.05). When CoBF remained above 20% of control flow during ischemia (2 rats) no AD or irreversible injury occurred. The present study suggests that AD is a more reliable determinant of irreversible brain injury than degree of CBF reduction, and also demonstrates that 15 min is the critical duration of AD for irreversible brain injury at brain temperatures around 37 degrees C.

An epidemiological survey of moyamoya disease, unilateral moyamoya disease and quasi-moyamoya disease in Japan

OBJECTIVES Moyamoya disease (MMD) is a unique occlusive disease of the bilateral internal carotid arteries in which, compensation for occlusion results in an enrichment of collateral arteries at the base of the brain. However, the epidemiology of unilateral MMD (typical angiographic evidence of MMD unilaterally with equivocal contralateral findings), and quasi-MMD (MMD present with inherited or acquired disorders) is poorly known. Here, a nationwide epidemiological survey was conducted to estimate the total numbers of patients, the annual incidence rates and prevalences of MMD, unilateral MMD and quasi-MMD in Japan. PATIENTS AND METHODS The neurosurgery, neurology and pediatrics departments that were listed in Japanese resident training programs were recruited to participate in this survey. Questionnaires were directly mailed to 2998 departments in February 2006. RESULTS A total of 1183 departments replied to the questionnaire (39.5% response rate). It was estimated that there were 6670.9 MMD patients, 840.5 unilateral MMD patients and 430.4 quasi-MMD patients in Japan. The annual incidence rates of MMD, unilateral MMD and quasi-MMD are 1.13, 0.23 and 0.11/100,000, respectively, and the prevalences are 5.22, 0.66 and 0.34/100,000, respectively. These patients were mainly treated by neurosurgeons. An estimated total of 929.1 surgical interventions are performed in Japan annually. CONCLUSION This nationwide study reports the current epidemiologic status of MMD, unilateral MMD and quasi-MMD in Japan.

Incidence and clinical features of symptomatic cerebral hyperperfusion syndrome after vascular reconstruction.

BACKGROUND Vascular reconstructions are the established treatment for ischemic cerebrovascular disease. Cerebral hyperperfusion syndrome (CHS) is occasionally seen after vascular reconstruction and manifest clinical symptoms. The purpose of this study is to investigate the incidence and clinical features of CHS after vascular reconstruction. METHODS A total of 144 patients with ischemic cerebrovascular disease (53 carotid endarterectomy [CEA] for carotid artery stenosis, 48 carotid artery stenting [CAS] for carotid artery stenosis, 20 bypass surgery for atherosclerotic cerebrovascular disease, 40 bypass surgery for moyamoya disease [MMD]) underwent vascular reconstruction. Patients were examined neurologically and radiologically, including computed tomography, magnetic resonance imaging, and single-photon-emission computed tomography, and then CHS was evaluated. RESULTS CHS developed in 1 (1.9%) CEA, 1 (2.1%) CAS, 1 (5.0%) bypass surgery for atherosclerotic cerebrovascular disease, and 6 (15.0%) bypass surgery for MMD. The incidence of CHS was significantly higher in patients with MMD. Aged patients and impairment of cerebrovascular reserve were correlated with CHS. Patients manifested disorientation after CEA and complained of headache after CAS. Diffuse hemispheric hyperperfusion was detected by single-photon-emission computed tomography. However, MMD patients manifested focal neurologic deficit, focal cerebral edema, and increased regional cerebral blood flow around vascular anastomosis. These patients were treated with blood pressure control and administration of free radical scavengers, and recovered without permanent deficits. CONCLUSIONS The incidence of CHS is significantly higher in patients with MMD and results in vasogenic edema visible on magnetic resonance imaging.

Assessment of Carotid Plaque Stability Based on the Dynamic Enhancement Pattern in Plaque Components With Multidetector CT Angiography

Background and Purpose— Recent studies have investigated plaque morphology to determine patients who are at high risk of carotid atherosclerosis. In this study, we investigated whether a difference in dynamic enhancement pattern in plaque components could be useful to assess plaque stability with multidetector CT angiography. Methods— Fifty-nine lesions with moderate to severe carotid atherosclerosis in 51 patients (33 symptomatic, 18 asymptomatic) were consecutively included. Early- and delayed-phase images were obtained in 3 equivalent axial slices with multidetector CT angiography. Hounsfield units (HU) in the early phase were subtracted from those in the delayed phase in plaques (&Dgr;HU) and compared with clinical features, MRI-based plaque characteristics, and histological findings with 20 surgical specimens acquired from carotid endarterectomy. Results— The &Dgr;HU was significantly higher in asymptomatic than that in symptomatic presentation (P=0.02). With MRI, a higher &Dgr;HU was negatively correlated with signal intensity on T1-weighted imaging (r=−0.56, P<0.0001). Histology confirmed that &Dgr;HU was positively correlated with fibrous tissue (r=0.67, P=0.001) and negatively correlated with a lipid-rich necrotic core with hemorrhage (r=−0.70, P<0.001). Moreover, less neovascularization and inflammation was found in plaques with a higher &Dgr;HU. Conclusions— Delayed-phase images provide information regarding the dynamic change in contrast media from the early arterial phase. An increase in HU from the early phase on multidetector CT angiography indicates plaque stability with more fibrous tissue and a less lipid-rich necrotic core, intraplaque hemorrhage, and neovascularization.

Detection of blood blister-like aneurysm and intramural hematoma with high-resolution magnetic resonance imaging.

Blood blister-like aneurysms (BBAs) tend to have a more precipitous clinical course, enlarging rapidly and rebleeding frequently. Nevertheless, they often present a diagnostic challenge because of the characteristic morphological features of a wide neck and shallow outpouching of the medial wall. The authors present the case of a 34-year-old woman who suffered a subarachnoid hemorrhage whose cause could not be determined on the initial imaging with digital subtraction (DS) angiography and CT angiography. Interestingly, MR imaging studies obtained on the 7th day revealed an intramural hematoma on the dorsal wall of the left internal carotid artery, which helped in the diagnosis of BBA on the third DS angiography study obtained on the 8th day, and in the surgical intervention on the 10th day. This case supports the hypothesis that focal dissection contributes to the formation of BBAs. Use of MR imaging in the subacute stage, in addition to DS and CT angiography, might be helpful in the diagnosis of BBAs.

Changes of neuronal transmission in the hippocampus after transient ischemia in spontaneously hypertensive rats and the protective effects of MK-801.

I studied the mechanism of postischemic neuronal degeneration in the hippocampus by an electrophysiological method. Methods Sequential changes of field potentials evoked by perforant path stimulation in the dentate gyrus and the CA1 region of the hippocampus were evaluated in spontaneously hypertensive rats up to 7 days after transient global ischemia induced by bilateral occlusion of the carotid arteries for 20 minutes after electrocauterization of the vertebral arteries. Animals were treated with vehicle or the excitotoxin antagonist (+)−5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10 amine (MK-801,2 mg/kg or 5 mg/kg) intraperitoneally 30 minutes before ischemia. Results Complete recovery of the population spike was observed in the dentate gyrus within 24 hours after recirculation, followed by a gradual reduction of population spike amplitude. In contrast, population spike in the CA1 region showed partial recovery 24 hours after recirculation, and an abrupt reduction of population spike amplitude occurred on day 2. There was no significant enhancement of population spike amplitude in either region throughout the experiment. Interneuronal recurrent inhibition in the dentate gyrus was enhanced on day 4, and ischemic changes were apparent in the CA1 pyramidal cells on day 7. Pretreatment with 5 mg/kg MK-801 prevented field potential and pathological changes completely in the dentate gyrus and partially in the CA1 region. Conclusions My results indicate that pathological changes of the CA1 pyramidal neurons after transient ischemia may not be the result of postischemic overstimulation. However, neuronal transmission in the CA1 region may be persistently impaired during or after transient ischemia.