Aki Shintani

Protection of dopamine neurons by bone marrow stromal cells.

Transplantation of bone marrow stromal cells (BMSC) has recently been demonstrated to provide neuroprotection in animal models of brain injuries such as ischemia and trauma. The present study was undertaken to explore whether BMSC can promote the survival of dopamine (DA) neurons in neuronal insult models in vitro. We also examined whether BMSC can increase the survival rate of embryonic DA neurons grafted into the striatum of a rat model of Parkinsons disease (PD). Treatment with conditioned media derived from BMSC cultures was found to significantly prevent the death of DA neurons in in vitro cell injury models such as serum deprivation and exposure to the neurotoxin 6-OHDA. In a transplantation study, we also found that the survival of grafted DA cells was significantly enhanced by treating donor cells with the conditioned media at the steps of both cell dissociation and implantation. The results suggest that BMSC may secrete diffusible factors able to protect DA neurons against neuronal injuries. Indeed, BMSC expressed mRNA encoding brain-derived neurotrophic factor, fibroblast growth factor-2 and glial cell line-derived neurotrophic factor, all of which have previously been shown to exhibit potent neurotrophic effects on DA cells. Enzyme-linked immunosorbent assay revealed that the cells release these growth factors into culture media. The present data indicate that BMSC may be a potential donor source of cell-based regenerative therapy for PD where the progressive loss of the midbrain DA neurons takes place.

Hemodynamic characteristics at the rupture site of cerebral aneurysms: a case study.

BACKGROUND AND IMPORTANCE Hemodynamics play an important role in the mechanisms of aneurysm formation, growth, and rupture. However, little is known about the hemodynamics of rupture sites. CLINICAL PRESENTATION We incidentally acquired 3-dimensional images before and at the moment of rebleeding of a cerebral aneurysm in a patient. Comparison of these 2 images enabled precise identification of the rupture site. On the basis of computational fluid dynamics simulation, we propose that there are characteristic hemodynamic parameters of the rupture site in cerebral aneurysms. We evaluated flow velocity, wall shear stress (WSS), pressure, and the oscillatory shear index to determine characteristic parameters at the rupture site. Among the hemodynamic parameters in the cardiac cycle, the rupture site was most markedly distinguished by a combination of low WSS at end diastole and high pressure at peak systole. The flow patterns around the rupture site uniquely changed in the cardiac cycle. The rupture site was an impingement zone at peak systole. Flow separation at the rupture site was observed at end diastole. CONCLUSION In this case, a region with low WSS at end diastole and high pressure at peak systole was at the rupture site. A possible mechanism of rupture in this particular aneurysm is that low WSS at end diastole caused degeneration and thinning of the aneurysm wall and that high pressure at peak systole (impingement zone) resulted in rupture of the thinning wall.

Endovascular recanalization of the completely occluded internal carotid artery using a flow reversal system at the subacute to chronic stage.

OBJECT The efficacy and pitfalls of endovascular recanalization were evaluated in cases of internal carotid artery (ICA) occlusion in the subacute to chronic stage. METHODS Fourteen cases (15 lesions) of symptomatic ICA occlusion with hemodynamic compromise or recurrent symptoms were treated at the subacute to chronic stage using an endovascular technique. The Parodi embolic protection system was used during the recanalization procedure to prevent embolic stroke by reversing the flow from the distal ICA to the common carotid artery. RESULTS Recanalization of the occluded ICA was possible in 14 of 15 lesions. The occlusion points were 10 cervical ICAs and 4 petrous/cavernous ICAs in successfully recanalized cases. Ischemic symptoms disappeared completely after the treatment, and new ischemic symptoms did not appear related to the treated lesion. Single photon emission computed tomography findings demonstrated the improvement of hemodynamic compromise in all cases. One case showed right middle cerebral artery branch occlusion during the procedure, but this patients neurological symptoms were stable due to preexisting hemiparesis. Endovascular recanalization was possible and effective in improving hemodynamic compromise. However, there are still several problems with this technique, such as hyperperfusion syndrome after recanalization, cerebral embolism during treatment, durability after treatment, and identification of the occlusion point before treatment. CONCLUSIONS Endovascular recanalization using an embolic protection device can be considered as an alternative treatment for symptomatic ICA occlusion with hemodynamic compromise or refractoriness to antiplatelet therapy, even in the subacute to chronic stage of the illness.

Hemodynamic Effects of Stent Struts versus Straightening of Vessels in Stent-Assisted Coil Embolization for Sidewall Cerebral Aneurysms

Background Recent clinical studies have shown that recanalization rates are lower in stent-assisted coil embolization than in coiling alone in the treatment of cerebral aneurysms. Objective This study aimed to assess and compare the hemodynamic effect of stent struts and straightening of vessels by stent placement on reducing flow velocity in sidewall aneurysms, with the goal of reducing recanalization rates. Methods We evaluated 16 sidewall aneurysms treated with Enterprise stents. We performed computational fluid dynamics simulations using patient-specific geometries before and after treatment, with or without stent struts. Results Stent placement straightened vessels by a mean (±standard deviation) of 12.9°±13.1° 6 months after treatment. Placement of stent struts in the initial vessel geometries reduced flow velocity in aneurysms by 23.1%±6.3%. Straightening of vessels without stent struts reduced flow velocity by 9.6%±12.6%. Stent struts had significantly stronger effects on reducing flow velocity than straightening (P = 0.004, Wilcoxon test). Deviation of the effects was larger by straightening than by stent struts (P = 0.01, F-test). The combination of stent struts and straightening reduced flow velocity by 32.6%±12.2%. There was a trend that larger inflow angles produced a larger reduction in flow velocity by straightening of vessels (P = 0.16). Conclusion In sidewall aneurysms, stent struts have stronger effects (approximately 2 times) on reduction in flow velocity than straightening of vessels. Hemodynamic effects by straightening vary in each case and can be predicted by inflow angles of pre-operative vessel geometry. These results may be useful to design a treatment strategy for reducing recanalization rates.

Stent-assisted coil embolization and computational fluid dynamics simulations of bilateral vertebral artery dissecting aneurysms presenting with subarachnoid hemorrhage: case report.

BACKGROUND AND IMPORTANCE A vertebral artery dissecting aneurysm (VADA) is a relatively rare cause of subarachnoid hemorrhage. Bilateral VADAs are even rarer, and management strategies are controversial. We report a case of bilateral VADAs presenting with subarachnoid hemorrhage. We treated the patient by stent-assisted coil embolization of both aneurysms at a single session on the basis of results of preoperative computational fluid dynamic simulations. CLINICAL PRESENTATION A 48-year-old man presented with subarachnoid hemorrhage resulting from bilateral VADAs. We treated the patient by stent-assisted coil embolization of both aneurysms at a single session. Before the treatment, we performed computational fluid dynamics simulations to predict the ruptured side. We also estimated the increase in wall shear stress on an aneurysm in case of trapping of another aneurysm, which might cause enlargement and rupture of the aneurysm. The treatment was performed successfully. The patient remains neurologically intact at 14 months from the onset. CONCLUSION Stent-assisted coil embolization of subarachnoid hemorrhage with bilateral VADAs for both sides is a reasonable treatment because it prevents rebleeding and preserves bilateral vertebral arteries without increasing hemodynamic stress. To the best of our knowledge, this is the first report to describe this type of treatment for bilateral VADAs with subarachnoid hemorrhage. Computational fluid dynamics simulations may be useful for developing treatment strategies for aneurysms.

Generation of dopamine neurons from embryonic stem cells in the presence of the neuralizing activity of bone marrow stromal cells derived from adult mice

Stromal cell lines such as PA6 and MS5 have been employed for generating dopamine (DA) neurons from embryonic stem (ES) cells. The present study was designed to test whether bone marrow stromal cells (BMSC) derived from adult mice might be available as a feeder layer to produce DA cells efficiently from ES cells. When ES cells were grown on BMSC in the presence of fibroblast growth factor 8 (FGF8) and sonic hedgehog (SHH), about 40% of TuJ1‐positive neurons expressed tyrosine hydroxylase (TH). Because these cells labeled with TH were negative for dopamine‐β‐hydroxylasae (DBH), the marker for noradrenergic and adrenergic neurons, the TH‐positive cells were most likely DA neurons. They indeed expressed midbrain DA neuron markers such as Nurr 1, Ptx‐3, and c‐ret and were capable of synthesizing and releasing DA in vitro. Furthermore, DA neurons differentiated from ES cells in this differentiation protocol survived transplantation in rats with 6‐hydroxydopamine lesions and reversed the lesion‐induced circling behavior. The data indicate that BMSC can facilitate an efficient induction of DA neurons from ES cells and that the generated DA neurons are biologically functional both in vitro and in vivo. Insofar as BMSC have recently been employed in autologous cell therapy for ischemic heart and arteriosclerotic limb diseases, the present study raises the possibility that autologous BMSC can be applied in future cell transplantation therapy in Parkinsons disease.

Stenting for Left Subclavian Artery Stenosis before and after Coronary Artery Bypass Grafting Using the Internal Mammary Artery A Report of Three Cases

Stenosis of the subclavian artery proximal to the origin of the internal mammary artery (IMA) used for coronary artery bypass grafting may produce flow reversal (steal syndrome) and cause myocardial ischemia. We present three cases of subclavian artery stenosis proximal to the IMA before and after CABG. The first case developed symptomatic myocardial ischemia resulting from a variant of coronary-subclavian steal syndrome. The second case had asymptomatic subclavian artery stenosis proximal to the IMA used for CABG. In the third case we planned to perform CABG using the left IMA to treat cardiac ischemia. All of the patients were successfully treated by stent placement without the use of a protection device. In the first and second cases, cardiac ischemia did not appear during balloon inflation of the subclavian artery and no embolic complication occurred. In the third case, CABG was performed six months after stenting. Subclavian artery stenting is a valid alternative to surgical treatment to restore the flow to the IMA before or after CABG.

Intraoperative hemorrhage in medulloblastoma: a case report and review of the literature

HeadingAbstract Object. We present the first case of intraoperative hemorrhage in a medulloblastoma. Case report. A 10-year-old girl presented with a 4-week history of headache, nausea, and vomiting. Radiological examination showed a space-occupying mass in the cerebellar vermis. Surgical removal was performed via a midline suboccipital approach. When the dura was incised and the occipital sinus was ligated after suboccipital craniectomy, bleeding occurred in the tumor. Macroscopically, hematoma was found only in the left part of the tumor and not in the right part. Microscopically, different architectures of tumor vessels, thin-walled and thick-walled, were found between the left part and the right part, respectively. The tumoral contents and hematoma were totally removed. Histological examination revealed a medulloblastoma. Conclusion. We experienced a very rare case of medulloblastoma in which intratumoral hemorrhage occurred during operation. We speculate that ligation of the occipital sinus and thin-walled vessels within the tumor might have caused the hemorrhage in our case.

Stent-Assisted Coil Embolization for Cavernous Carotid Artery Aneurysms

Internal carotid artery (ICA) occlusion with or without a bypass surgery is the traditional treatment for cavernous sinus (CS) aneurysms with cranial nerve (CN) dysfunction. Coil embolization without stents frequently requires retreatment because of the large size of CS aneurysms. We report the mid-term results of six unruptured CS aneurysms treated with stent-assisted coil embolization (SACE). The mean age of the patients was 72 years. The mean size of the aneurysms was 19.8 mm (range: 13–26 mm). Before treatment, four patients presented with CN dysfunction and two patients had no symptoms. SACE was performed under local or general anesthesia in three patients each. Mean packing density was 29.1% and tight packing was achieved. There were no neurological complications. CN dysfunction was cured in three patients (75%) and partly resolved in one patient (25%). Transient new CN dysfunction was observed in two patients (33%). Clinical and imaging follow-up ranged from 6 to 26 months (median: 16 months). Recanalization was observed in three patients (50%; neck remnant in two patients and dome filling in one patient), but no retreatment has yet been required. No recurrence of CN dysfunction has occurred yet. In summary, SACE increases packing density and may reduce requirement of retreatment with an acceptable cure rate of CN dysfunction. SACE may be a superior treatment for coiling without stents and be an alternative treatment of ICA occlusion for selected patients, such as older patients and those who require a high-flow bypass surgeryor cannot receive general anesthesia.

Jargonagraphia with severe aphasia due to a right hemisphere lesion: case report.

The authors report a case of a patient who developed jargonagraphia, severe aphasia, unilateral spatial neglect and apraxia due to a right hemisphere lesion. Jargonagraphia with severe aphasia, unilateral spatial neglect and apraxia is quite rare. The mechanisms of jargonagraphia remain unknown. A possible mechanism underlying this case of jargonagraphia is discussed.