Takahito Okazaki

Intravenous administration of bone marrow stromal cells increases survivin and Bcl-2 protein expression and improves sensorimotor function following ischemia in rats

Intravenous administration of bone marrow stromal cells (MSCs) in animal models with focal cerebral ischemia has been found to be effective in attenuating neuronal damage. We examined whether intravenously transplanted MSCs alters expression of apoptosis-related proteins. Fisher-344 rats were subjected to 90-min middle cerebral artery occlusion (MCAO). The experimental groups were: (I) vehicle group, with intravenous injection of phosphate-buffered saline (PBS) 3h after MCAO; and (II) transplant group, with intravenous injection of MSCs (3x10(6)cells) 3h after MCAO. Neurological function of rats was evaluated using modified neurological severity score (mNSS) and Rotor-rod Motor Test (RMT). Rats were sacrificed on 1st, 3rd and 7th days of MCAO, and coronal brain sections were stained immunohistochemically to identify the apoptosis-related proteins, namely survivin and Bcl-2. We also examined Terminal Deoxynucleotidyl Transferase-Mediated dUTP-biotin Nick End Labeling (TUNEL)-positive cells on 3rd day of MCAO. Functional recovery according to mNSS and RMT was significantly better in the transplant group as compared with the vehicle group (P<0.05). Immunohistochemical analysis revealed significant expression of survivin on 3rd day and Bcl-2 on 1st and 3rd days in the transplant group. The vehicle group displayed significantly more TUNEL-positive cells than the transplant group on 3rd day (P<0.05). These results suggest that intravenous transplantation of MSCs prevents down-regulation of survivin and Bcl-2 preventing apoptosis and cell death in the ischemic brain leading to motor and sensory function recovery.

Characteristics of aneurysms of the internal carotid artery bifurcation.

SummaryBackground. Arterial bifurcations are sites of maximal hemodynamic stress, where cerebral aneurysms commonly develop. However, in our experience with endovascular treatment for aneurysms of the internal carotid artery (ICA) bifurcation, we often experienced that the aneurysmal neck did not necessarily exist only at the ICA bifurcation (ICBi). In this study, we have retrospectively evaluated characteristics of aneurysms at the ICBi.Methods. Ten ICBi aneurysms in 10 consecutive patients were studied retrospectively. The size of the aneurysms, the angles formed between the ICA and the anterior cerebral artery (ACA) and middle cerebral artery (MCA), and the diameter of the ICA, ACA and MCA were measured. Furthermore, to study the relationship between the location of the aneurysmal neck and the bifurcation of the ICA, the distance between the midline of the aneurysmal neck and of the ICA was measured.Results. The average aneurysm size was 6.3 ± 3.2 mm and the average neck was 3.1 ± 1.2 mm. The average ICA-ACA angle was 57.3 ± 16.5 degrees, and the average ICA-MCA angle was 128.9 ± 24.1 degrees. The average diameters of the ICA, ACA and MCA were 2.9 ± 0.5 mm, 1.9 ± 0.4 mm and 2.5 ± 0.4 mm, respectively. The average distance between the midline of the aneurysmal neck and the ICA was 1.6 ± 0.6 mm, and all aneurysmal necks of the ICBi arose from the side of the ACA.Conclusion. ICBi aneurysms were deviated to the side of the A1 segment of the ACA, where the artery might suffer higher hemodynamic stress.

Churg-Strauss syndrome presenting with subarachnoid hemorrhage from ruptured dissecting aneurysm of the intracranial vertebral artery

Churg-Strauss syndrome (CSS) represents a rare systemic vasculitis that is almost invariably accompanied by bronchial asthma and eosinophilia. We report a case of a 36-year-old woman with previously diagnosed CSS presented with subarachnoid hemorrhage (SAH) from dissecting aneurysm in a vertebral artery (VA). Two months before onset of SAH, the patient had presented with numbness on her right lower leg due to peripheral neuropathy. On admission, angiography revealed dissecting aneurysm of the right intracranial VA and stenosis of the basilar artery. Hematological examination revealed an increased percentage of eosinophils. Ruptured dissecting aneurysm of the intracranial VA was diagnosed. Emergent coil embolization of the dissecting aneurysm and occlusion of the parent artery was performed to prevent repeated hemorrhage from the dissecting aneurysm. Then pharmacotherapy with prednisone was initiated for CSS. The patient recovered well and was discharged without any neurological deficit. As far as we know, this is the first reported case of CSS presented with SAH from dissecting aneurysm on posterior circulation.

Effects of simulated microgravity on proliferation and chemosensitivity in malignant glioma cells

A three-dimensional (3D) clinostat is a device for generating multidirectional G force, resulting in an environment with an average of 10(-3)G. We cultured human malignant glioma cell lines in a 3D-clinostat (CL group) and examined the growth properties and chemosensitivity of the cells compared to cells cultured under normal 1G conditions (C group). The growth rate was significantly inhibited in the CL group, but without cell cycle change. Mitochondrial activity was also inhibited in the CL group. Thus, inhibition of malignant glioma proliferation occurred that could be attributed to deceleration of mitosis. Chemosensitivity to cisplatin (cis-diamminedichloroplatinum(II), CDDP) in the CL group was significantly enhanced compared to the C group. This method has significant potential as a treatment of malignant gliomas and a tool for understanding developmental biology.

Generation of bone marrow-derived neural cells in serum-free monolayer culture

Bone marrow-derived cells (BMCs) are reported to trans-differentiate into neural lineages, and are expected to offer a valuable resource for treating severe diseases of the central nervous system. BMCs that show neural differentiation may differ morphologically from typical marrow stromal cells. The present study aimed to obtain efficient generation of cells with neural features from bone marrow. Serum-free culture was applied to BMCs to prevent the growth of differentiated cells. Using basic fibroblast growth factor and extracellular matrix, rodent BMCs capable of proliferation and neural differentiation expanded in monolayer form. Cultured cells were small, round or spindle-shaped, and expressed nestin. Under neural differentiation conditions, cells developed long, thin cellular processes with branches, and expressed neuronal and glial phenotypes. Intracerebrally transplanted BMCs survived and migrated into the subcortex of syngenic animals.

Carotid artery stenting for vulnerable plaques on MR angiography and ultrasonography: utility of dual protection and blood aspiration method

Background Carotid artery stenting (CAS) for internal carotid artery (ICA) stenosis with vulnerable plaques is controversial. We analyzed the effect of a dual protection and blood aspiration method during CAS in patients with vulnerable plaques. Methods A total of 111 patients with ICA stenosis underwent CAS using the dual protection (simultaneous flow reversal and distal filter) and blood aspiration method. In 103 of 111 patients, preoperative carotid plaque was estimated by both 3 T MRI and ultrasonography (US). ICA plaques with a high intensity signal on time-of-flight-MR angiography (TOF-MRA) and/or mobile component on US were defined as vulnerable plaques. We assessed major adverse events (MAE) (ie, major stroke, myocardial infarction, and death) and hyperintense spots on diffusion-weighted images (DWI) after CAS. We then evaluated the visible debris captured by dual protection and blood aspiration during CAS. Results The preoperative ICA plaque on TOF-MRA and US was judged to be vulnerable in 48.5% (50/103 patients). The success rate of the CAS procedure was 100% with no MAE within 30 days. DWI showed small hyperintense spots in 18% (9/50 patients) and 18.9% (10/53 patients) in the vulnerable and non-vulnerable plaque groups, respectively. Visible debris was captured in 68% (34/50 patients) and 45.3% (24/53 patients) in the vulnerable and non-vulnerable plaque groups, respectively (p=0.0286). Conclusions The combination of dual protection and blood aspiration could provide effective distal embolic protection although vulnerable plaques on TOF-MRA and US had a high incidence of debris during CAS. Thus, CAS using dual protection and blood aspiration is safe in patients with vulnerable plaques.

A Rare Case of Shunt Malfunction Attributable to a Broken Codman-Hakim Programmable Shunt Valve after a Blow to the Head

We report a rare case of shunt malfunction resulting from breakage of the Codman-Hakim programmable shunt valve system following a blow to the head. Originally, the patient had suffered intraventricular hemorrhage a month after birth; ventriculoperitoneal shunt was performed at 7 months. After that, the shunt valve functioned well for 7 years. The patient presented with headaches after receiving a blow behind the right ear. The headache became exacerbated with activity and improved with rest. Damage to the shunt valve was identified during surgery, with a crack at the top of the valve housing. Symptoms resolved following a change of the complete shunt system. The possibility of damage to the shunt valve following a blow should be considered in shunt patients presenting with headaches.

Carotid artery stenting in a patient with right-sided aortic arch with an aberrant left subclavian artery

A right-sided aortic arch with an aberrant left subclavian artery is a rare anatomical variation. We report a case treated with carotid artery stenting (CAS) for a patient with a right-sided aortic arch with an aberrant left subclavian artery. A 72-year-old man presented right hemiparesis due to acute brain infarction. Neck CT angiography showed 70% stenosis in the left internal carotid artery (ICA). We diagnosed acute brain infarction as artery-to-artery embolism due to ICA stenosis and decided to perform carotid artery stenting (CAS) for symptomatic ICA stenosis. CT angiography to evaluate an access route to the lesion incidentally showed the right-sided aortic arch with an aberrant left subclavian artery. An intraoperative aortogram showed a right-sided aortic arch. The guiding catheter was carefully introduced up to the left common carotid artery. CAS was performed with a proximal balloon and distal filter protection. The stenotic area was restored, and the patient was discharged without suffering recurrent attacks. Although a right-sided aortic arch with an aberrant left subclavian artery is a very rare anatomical variation, it can be encountered in neuroendovascular treatment, and therefore knowledge of this anatomical variation is important.

Course of apparent diffusion coefficient values in cerebral edema of dural arteriovenous fistula before and after treatment.

Apparent diffusion coefficient (ADC) values at magnetic resonance imaging (MRI) are useful to distinguish vasogenic and cytotoxic edema due to cerebovascular diseases. Dural arteriovenous fistulas (DAVFs) with retrograde leptomeningeal venous drainage may cause cerebral edema by venous congestion. We report herein the course of ADC values of cerebral edema before and after endovascular treatment in DAVFs. A 65-year-old woman with transverse-sigmoid (T-S) sinus DAVFs with retrograde leptomeningeal venous drainage presented with severe edema in cerebellar hemisphere and brainstem. In preoperative MRI, increased ADC values were observed in the edema area. The isolated sinus was obliterated completely by transvenous embolization. On the following day after treatment, the ADC values in cerebral edema area increased slightly without any new neurological deficits and improved at 1 week later. Rapid resolution of venous congestion due to DAVFs may cause a slight, transient progression of vasogenic edema.

Vascular Wall Imaging of Unruptured Cerebral Aneurysms with a Hybrid of Opposite-Contrast MR Angiography

BACKGROUND AND PURPOSE: Inflammation and degeneration of the intracranial saccular aneurysm wall play a major role in aneurysm formation, development and subsequent rupture. The aim of this study was to characterize the walls of unruptured intracranial aneurysms by using a hybrid of opposite-contrast MRA at 3T. MATERIALS AND METHODS: Fourteen consecutive patients with 17 unruptured intracranial aneurysms who initially underwent clipping surgery were prospectively evaluated. All aneurysms were scanned preoperatively by using a hybrid of opposite-contrast MRA in 3T high-resolution MR imaging. We classified intraoperative findings of atherosclerotic plaques in the aneurysms into 3 grades: grade A (major plaques), grade B (minor plaques), and grade C (no plaques). The contrast ratio of the high-intensity area was also measured relative to the background low-intensity area inside the carotid artery. RESULTS: Findings from preoperative plaque imaging of the aneurysm corresponded to the intraoperative findings in 15 of 16 aneurysms (excluding 1 that was impossible to visualize in its entirety due to anatomic reasons). Overall sensitivity and specificity of the hybrid of opposite-contrast MRA were 88.9% and 100%, respectively. During the operation, 4 aneurysms were classified as grade A; 5, as grade B; and 7, as grade C. The means of the contrast ratio for grades A, B, and C were 0.72 ± 0.03, 0.34 ± 0.30, and −0.02 ± 0.09, respectively. CONCLUSIONS: The hybrid of opposite-contrast MRA can detect visible atherosclerotic plaques in the unruptured aneurysm wall, and the contrast ratio in intracranial aneurysms correlated with their presence and extent. A study including a larger series is needed to validate the diagnostic potential of this imaging technique.