研究者詳細 - 杉生　憲志

Fenestration of the supraclinoid internal carotid artery with associated aneurysm

Keisuke Onoda, Shigeki Ono, Koji Tokunaga, Kenji Sugiu, Isao Date

NEUROLOGIA MEDICO-CHIRURGICA 48 ( 3 ) 118 - 120 2008年3月

記述言語：英語出版者・発行元：JAPAN NEUROSURGICAL SOC

A 42-year-old woman presented with a rare case of fenestration of the supraclinoid internal carotid artery (ICA) with associated aneurysm manifesting as headache. Computed tomography (CT) found no abnormalities. Three-dimensional CT angiography showed fenestration of the left ICA with an associated aneurysm. Direct surgery was performed for the aneurysm, and the patient's postoperative course was uneventful. The present case of ICA fenestration associated with aneurysm indicates that surgical treatment should be considered for even small unruptured aneurysms arising from this location, because of the high risk of rupture.

DOI： 10.2176/nmc.48.118

Effects of deferoxamine-activated hypoxia-inducible factor-1 on the brainstem after subarachnoid hemorrhage in rats 国際誌

Tomohito Hishikawa, Shigeki Ono, Tomoyuki Ogawa, Koji Tokunaga, Kenji Sugiu, Isao Date

NEUROSURGERY 62 ( 1 ) 232 - 240 2008年1月

記述言語：英語出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

OBJECTIVE: Hypoxia-inducible factor (HIF)-1 is a transcription factor that regulates the expression of various neuroprotective genes. The goal of this study was to clarify the relationship between HIF-1 expression and subarachnoid hemorrhage (SAH) and to characterize the effects of deferoxamine (DFO)-induced increases in HIF-1 protein levels on the brainstem and the basilar artery (BA) after experimental SAH.
METHODS: Rat single- and double-hemorrhage models (injected on Days 0 and 2) of SAH were used. We assessed the time courses for HIF-1 protein levels in the brainstems and the BA diameters within 10 minutes and 6 hours on Days 1 and 2 in the single-SAH model, and also on Day 7 in the double-SAH model. After induction of double hemorrhage in rats, DFO was injected intraperitoneally. We then evaluated HIF-1 protein expression and brainstem activity, BA diameter, and brainstem blood flow.
RESULTS: After the rats experienced SAH, HIF-1 protein expression was significantly greater at 10 minutes in the single-injection model and at 7 days in the double-injection model than at similar time points in the control group, and these increases correlated with degrees of cerebral vasospasm. DFO injection resulted in significant increases in HIF-1 protein expression and activity in the brainstems of rats with SAH, compared with the rats with SAH that were given placebos, and the rats without SAH in the double-hemorrhage model. Cerebral vasospasm and reduction of brainstem blood flow were significantly attenuated in the rats that were administered DFO.
CONCLUSION: These results show that a DFO-induced increase in HIF-1 protein level and activity exerts significant attenuation of BA vasospasm and reduction of brainstem blood flow in the rat model of SAH. DFO may be a promising agent for treating clinical SAH.

DOI： 10.1227/01.NEU.0000296989.61911.81

Continuous evaluation of regional oxygen saturation in cerebral vasospasm after subarachnoid haemorrhage using INVOS (R), portable near infrared spectrography

S. Ono, S. Arimitsu, T. Ogawa, H. Manabe, K. Onoda, K. Tokunaga, K. Sugiu, I. Date

CEREBRAL VASOSPASM: NEW STRATEGIES IN RESEARCH AND TREATMENT 104 215 - 218 2008年

記述言語：英語出版者・発行元：SPRINGER-VERLAG WIEN

Background. Although several tools are available for the detection of cerebral vasospasm after subarachnoid haemorrhage, it has remained difficult to identify vasospasm timely and accurately. INVOS (R) monitoring measures the oxygen saturation by using near infrared spectroscopy, and in this study we examined the usefulness of this system for the detection of vasospasm.
Method. Five patients who had suffered SAH were enrolled in this study. In view of the thickness of the clots, the probes of INVOS (R) were attached to the scalp in the areas where vasospasm was likely to occur, from day 3 to the end of vasospasm, up to 14 days post SAH. Patients were monitored every day by INVOS 0) and by neurological exams. Angiography was performed if regional oxygen saturation had continuously decreased by 10% or more as compared to the contralateral side, or if patients showed additional neurological deficits. If vasospasm was detected, interventional treatment using intraarterial fasudil injection or percutaneous, transluminal angioplasty was performed. The same interventional therapy was repeated until neurological deficits improved.
Findings. When the INVOS (R) value decreased to lower than 60, angiographic or symptomatic vasospasm tended to occur, and the response of regional oxygen saturation correlated accurately, both symptomatically and angiographically, with brain ischemia due to vasospasm. Recovery from ischemia on angiography or single photon emission CT also correlated with the return of regional oxygen saturation by INVOS (R).
Conclusions. INVOS (R) monitoring is handy and noninvasive; it is able to evaluate real-time regional oxygen saturation in the region of VS and may be superior to the other existing monitoring systems.

DOI： 10.1007/978-3-211-75718-5-41

Endovascular treatment for ruptured cerebral aneurysms in elderly patients.

Sugiu K, Tokunaga K, Nishida A, Hayase H, Ono S, Onoda K, Date I

Journal of Stroke & Cerebrovascular Disease 17 ( (5)Supplement 1 ) S92 2008年

塞栓物質の選び方と使用方法 2. コイル.

杉生憲志

IVR 23 ( -2 ) 195 - 198 2008年

頸動脈ステント留置術と抗血小板療法.

平松匡文, 杉生憲志, 徳永浩司, 西田あゆみ, 早瀬仁志, 菱川朋人, 小野成紀, 三好康之, 伊達勲

新薬と臨床 57 ( -12 ) 1987 - 1993 2008年

記述言語：日本語出版者・発行元：(株)医薬情報研究所

頸動脈ステント留置術(CAS)の初期治療成績と、周術期の抗血小板療法の実際について報告した。頸動脈狭窄症に対して、脳保護フィルターを使用して自己拡張型ステントを留置した50例を対象とした。術前狭窄率はNASCET法で60〜95(平均83)%であったが、術後狭窄率は0〜30(平均8)%に改善した。mRSは、術直後に悪化した症例は5例あったが、24時間後も悪化した状態が継続した症例は1例のみであった。CASの周術期における抗血小板剤の投与については、アスピリン、クロピドグレル、チクロピジン、シロスタゾールの中から、複数の抗血小板剤をCAS施行3日以上前から投与された。

内頸動脈海綿静脈洞部巨大・大型動脈瘤に対する複合治療.

伊達勲, 徳永浩司, 杉生憲志

脳卒中の外科 36 ( 1 ) 12 - 18 2008年

記述言語：日本語出版者・発行元：The Japanese Society on Surgery for Cerebral Stroke

Most patients with intracavernous large and giant aneurysms show cranial nerve signs, and a variety of surgical treatments have been developed. From the viewpoint of multimodality therapy, a combination of bypass and IC ligation or a combination of intravascular therapy and surgery has been performed. <br> We studied 29 consecutive patients with intracavernous large and giant aneurysms during the past 15 years. All the patients presented with cranial nerve signs. Therapeutic modalities for each patient were selected depending on anatomical features of the aneurysm on radiological examinations and neurological/hemodynamic conditions during balloon test occlusion (BTO). <br> ICAs were occluded surgically or endovascularly in 6 patients without bypass surgery. ICA ligation was simultaneously combined with high-flow bypass in 4 patients or with STA-MCA anastomosis in 14 patients, in which 2 patients developed delayed ischemic neurological symptoms due to emboli from the thrombosed aneurysms. STA-MCA anastomosis followed by internal coil trapping of the aneurysm under antiplatelet and anticoagulant therapy was successfully performed in 2 recent patients. Pre-operative neurological symptoms ameliorated when treatment was initiated within 3 months after the onset of symptoms.<br> Favorable clinical outcomes can be expected for patients with an intracavernous large or giant ICA aneurysm treated surgically or endovascularly based on adequate pre-operative radiological, neurological and hemodynamic evaluations. The treatment algorithm for the management of intracavernous large or giant aneurysms of ICA should be reviewed and revised according to the development of new devices and techniques.<br>

DOI： 10.2335/scs.36.12

CiNii Article

Endothelial nitric oxide synthase-11R protein therapy for prevention of cerebral vasospasm in rats: a preliminary report

T. Ogawa, S. Ono, T. Ichikawa, S. Arimitsu, K. Onoda, K. Tokunaga, K. Sugiu, K. Tomizawa, H. Matsui, I. Date

CEREBRAL VASOSPASM: NEW STRATEGIES IN RESEARCH AND TREATMENT 104 165 - + 2008年

記述言語：英語出版者・発行元：SPRINGER-VERLAG WIEN

Background. In one of our studies we found that enhanced green fluorescent protein (EGFP) fused with consecutive 11 arginines (11R), one of the protein transduction domains (PTDs) [1-6, 11], and effectively penetrated into all layers of the rat basilar artery (BA). We examined whether eNOS (140-kDa) fused 11R (11R-eNOS) was also transduced into the BAs and had a positive effect on the attenuation of cerebral vasospasm.
Method. 11R-eNOS or saline was injected into the cisterna magna of male Sprague-Dawley rats. Two hours after the injection, the BAs were extracted from the rats and transduction efficacy of 11R-eNOS in the BA was evaluated by immunofluorescence staining. To examine the effect of 11R-eNOS on the cerebral arteries exposed to SAH, we measured the post SAH BA diameters six hours after the injection of 11R-eNOS.
Findings. Immunofluorescent study confirmed the presence of 11ReNOS protein in the layers of the cerebral arteries in vivo. 11R-eNOS had a positive effect on attenuation of cerebral vasospasm.
Conclusions. 11R-eNOS was effectively transduced into the walls of the BA. 11R-eNOS inhibited the vasoconstriction after SAH. These results suggest that 11R-eNOS protein therapy has a potential in treating cerebral vasospasm.

DOI： 10.1007/978-3-211-75718-5-32

Direct protein transduction method to cerebral arteries by using 11R: new strategy for the treatment of cerebral vasospasm after subarachnoid haemorrhage

T. Ogawa, S. Ono, T. Ichikawa, H. Michiue, S. Arimitsu, K. Onoda, K. Tokunaga, K. Sugiu, K. Tomizawa, H. Matsui, I. Date

CEREBRAL VASOSPASM: NEW STRATEGIES IN RESEARCH AND TREATMENT 104 161 - + 2008年

記述言語：英語出版者・発行元：SPRINGER-VERLAG WIEN

Background. Gene transfer with some vectors may be useful for treatmcnt of cerebral vasospasm after subarachnoid haemorrhage (SAH) [2, 3, 6, 10, 12, 13, 19]. However, this method has some safety problems [18]. Previous studies have shown that direct delivery of therapeutic proteins by using protein transduction domain (PTD) may reduce these problems [14, 15]. Here, we examined the transduction efficiency of eleven consecutive arginines (11R), which is one of the most effective PTD 18, 91, into the rat cerebral arteries by using 11R-enhanced-green fluorescent protein (11R-EGFP).
Method. 11R-EGFP or EGFP was injected into the cisterna magna of the rats with SAH. SAH model was made by autologous blood injection. The proteins were injected just after the autologous blood injection in SAH rats. The expression of 11R-EGFP or EGFP was observed by fluorescence microscope.
Findings. The signal of 11R-EGFP was much stronger than that of EGFP in all the layers of the rat basilar artery (BA). The 11R-EGFP was especially transduced into the tunica media of the basilar artery 2 It after the injection.
Conclusions. Our results demonstrate that 11R-fused fluorescent protein effectively penetrates into the all layers of the rat BA, and especially into the tunica media.

DOI： 10.1007/978-3-211-75718-5-31

Effect of deferoxamine-activated hypoxia inducible factor-1 on the brainstem following subarachnoid haemorrhage

S. Ono, T. Hishikawa, T. Ogawa, M. Nishiguchi, K. Onoda, K. Tokunaga, K. Sugiu, I. Date

CEREBRAL VASOSPASM: NEW STRATEGIES IN RESEARCH AND TREATMENT 104 69 - 73 2008年

記述言語：英語出版者・発行元：SPRINGER-VERLAG WIEN

Background. Hypoxia inducible factor-1 (HIF-1) is a transcription factor that regulates the expression of various neuroprotective genes. The goal of this study was to clarify the relationship between HIF-1 a expression and subarachnoid haemorrhage (SAH) and to determine the effects of the deferoxamine (DFO)-induced increase in HIF-1 alpha protein levels on the brainstem and the basilar artery (BA) following experimental SAH.
Method. Rat single- (10min, 6h, Day 1, Day 2) and double-haemorrhage (Day 7) models of SAH were used. The time course of HIF-1 alpha protein levels of the brainstems and the diameter of the BA was assessed. After an induction of double-haemorrhage in rats, DFO was injected intraperitoneally and HIF-1 alpha protein expression, activity in the brainstems, the diameter of the BA and the brainstem blood flow were assessed.
Findings. The expression of HIF-1 alpha protein was significantly greater at 10 min and 7 days after SAH. The increase of HIF-1 alpha protein correlated with the degree of cerebral vasospasm. An injection of DFO resulted in significant increases it) HIF-1 alpha protein expression and activity in the brainstem of rats with SAH.
Conclusions. These results indicate that DFO-induced increase in HIF-1 alpha protein levels and activity exerts neuroprotective and antivasospastic effects. DFO may be a potential therapeutic tool for cerebral vasospasm after SAH.

DOI： 10.1007/978-3-211-75718-5-13

頸部内頸動脈狭窄症におけるCEAとCAS術後の医用画像を用いた患者特異的モデルと仮想モデルの流体力学シミュレーション

早瀬仁志, 中山敏男, 徳永浩司, 杉生憲志, 西田あゆみ, 有光帥二, 菱川朋人, 小野成紀, 太田信, 伊達勲

日本脳神経外科学会総会抄録集(CD-ROM) 67th 2008年

Triple-catheter technique in the transvenous coil embolization of an isolated sinus dural arteriovenous fistula 国際誌

Kenji Sugiu, Koji Tokunaga, Ayumi Nishida, Wataru Sasahara, Kyoichi Watanabe, Shigeki Ono, Keisuke Onoda, Isao Date

NEUROSURGERY 61 ( 3 ) 81 - 85 2007年9月

記述言語：英語出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

OBJECTIVE: Dural arteriovenous fistulae involving the transverse-sigmoid sinus, which is occluded at its proximal and distal ends (i.e., an isolated sinus), carry a high risk of intracranial hemorrhage or progressive neurological deficits. Although transvenous coil embolization is a useful and safe,treatment for such lesions, it is often difficult to reach into the isolated sinus through the occluded sinus using the percutaneous catheter approach.
METHODS: We report the successful treatment of two patients with transverse-sigmoid dural arteriovenous fistulae with isolated sinus using the percutaneous transvenous triple-catheter technique. A 6-French guiding catheter was placed at the internal jugular vein followed by a second 4-French catheter positioned at the end of the occluded sinus. A third microcatheter was then navigated into the isolated sinus with support of the second catheter.
RESULTS: Although initial attempts to reach into the isolated sinus without the second catheter failed, insertion of the second catheter resulted in successful navigation of the third microcatheter into the affected sinus in both cases. Complete cure was obtained in both cases by coil packing of the affected sinus.
CONCLUSION: Although careful maneuvering is required, this triple-catheter technique is useful for treatment of dural arteriovenous fistulae with isolated sinus.

DOI： 10.1227/01.NEU.0000279984.56050.70

Antivasospastic and antiinflammatory effects of caspase inhibitor in experimental subarachnoid hemorrhage 国際誌

Keiichi Iseda, Shigeki Ono, Keisuke Onoda, Motoyoshi Saroh, Hiroaki Manabe, Mitsuhisa Nishiguchi, Kenji Takahashi, Koji Tokunaga, Kenji Sugiu, Isao Date

JOURNAL OF NEUROSURGERY 107 ( 1 ) 128 - 135 2007年7月

記述言語：英語出版者・発行元：AMER ASSOC NEUROLOGICAL SURGEONS

Object. Inflammation in the subarachnoid space and apoptosis of arterial endothelial cells have been implicated in the development of delayed cerebral vasospasm after subarachnoid hemorrhage (SAH). The authors investigated mechanisms of possible antivasospastic effects of N-benzyl-oxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK), a caspase inhibitor that can inhibit both inflammatory and apoptotic systems., in animal models of SAH.
Methods. Rabbits were assigned to three groups of eight animals each and were subjected to SAH by injection of blood into the cisterna magna. The experiments were performed in the following groups: SAH only, SAH + vehicle, and SAH + Z-VAD-FMK. The Z-VAD-FMK (1 mg) or vehicle (5% dimethyl sulfoxide) was intrathecally administered before SAH induction. Diameters of the basilar artery (BA) were measured on angiograms obtained before and 2 days after SAH. The BA diameter on Day 2 was expressed as a percentage of that before SAH. Interleukin (IL)-1 beta in the cerebrospinal fluid (CSF) was examined using Western blotting, and brains were immunohistochemically examined for caspase-1 and IL-1 beta. In a separate experiment, 20 rats were subjected to SAH and their brains were immunohistochemically assessed for caspase-1, IL-1 beta, and macrophages.
Results. In rabbits, Z-VAD-FMK significantly attenuated cerebral vasospasm (the BA diameter on Day 2 in SAH-only, SAH + vehicle, and SAH + Z-VAD-FMK groups was 66.6 +/- 3.2%, 66.3 +/- 3.7%, and 82.6 +/- 4.9% of baseline, respectively), and suppressed IL-1 beta release into the CSF and also suppressed immunoreactivities of caspase- I and IL-1 beta in macrophages infiltrating into the subarachnoid space. Immunoreactivities for caspase- I and IL-1 beta were observed in immunohistochemically proven infiltrating macrophages in rats.
Conclusions. These results indicate that caspase activation may be involved in the development of SAH-induced vasospasm through inflammatory reaction.

DOI： 10.3171/JNS-07/07/0128

Packing efficacy of hydrocoil embolic system: in vitro study using ruptured aneurysm model 国際誌

Kyoichi Watanabe, Kenji Sugiu, Koji Tokunaga, Wataru Sasahara, Shigeki Ono, Isao Date

NEUROSURGICAL REVIEW 30 ( 2 ) 127 - 130 2007年4月

記述言語：英語出版者・発行元：SPRINGER

After endovascular coil embolization of cerebral aneurysms, coil compaction and late aneurysm recanalization have been ever observed. The HydroCoil Embolic System (HES) was developed to improve the packing efficacy of endovascular treatment of cerebral aneurysms. In this study, we evaluate the packing efficacy of HES using a silicone model of ruptured cerebral aneurysm. This silicone model was connected to a pulsatile flow pump and embolized with the initial framing coils followed by hydro coils (n = 3) or bare platinum coils (n = 3). The coils used in the two groups were identical to each other in size and length. In the hydro coil group, continuous outflow from ruptured aneurysm ceased in two out of three cases. On the other hand, in the bare platinum coil group, outflow from the ruptured point slightly decreased but did not stop in all cases. The hydro coil could result in a higher initial occlusion rate of silicone model. In addition, expanded hydrogel possibly sealed the ruptured point directly. Changes in the size of aneurysms were not detected, from which the risk of over-expansion seemed extremely low. The hydro Coil is a safe and feasible device for improving the packing efficacy in endovascular coil embolization.

DOI： 10.1007/s10143-007-0066-8

Novel protein transduction method by using 11R - An effective new drug delivery system for the treatment of cerebrovascular diseases 国際誌

Tomoyuki Ogawa, Shigeki Ono, Tomotsugu Ichikawa, Seiji Arimitsu, Keisuke Onoda, Koji Tokunaga, Kenji Sugiu, Kazuhito Tomizawa, Hideki Matsui, Isao Date

STROKE 38 ( 4 ) 1354 - 1361 2007年4月

記述言語：英語出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

Background and Purpose-A motif of 11 consecutive arginines (11R) is reported to be one of the most effective protein transduction domains for introducing proteins into the cell membrane. We therefore examined the transduction efficiency of 11R in cerebral arteries.
Methods-Basilar arteries (BAs) obtained from rats were incubated with either 11R-enhanced green fluorescent protein (11R-EGFP) or EGFP without 11R. After incubation, expression of 11R-EGFP or EGFP in BA serial sections was observed by fluorescence microscope. In an additional in vivo experiment, 11R-EGFP or EGFP was injected into the cisterna magna with or without subarachnoid hemorrhage. The 11R-EGFP or EGFP was injected just after the autologous blood injection, and then the expression of 11R-EGFP or EGFP in BA sections was also observed by fluorescence microscope.
Results-The 11R-EGFP signal was much stronger than that of EGFP in all layers of the rat BA, in both in vivo and ex vivo experiments. Moreover, the 11R-EGFP was transduced into the BA immediately ( 2 hours after the injection). Interestingly, 11R-fused fluorescent protein was transduced especially into the tunica media of the BA.
Conclusions-The 11R-fused fluorescent protein effectively penetrates into all layers of the rat BA, especially into the tunica media. This is the first study to our knowledge to demonstrate the successful transduction of a protein transduction domain fused protein into the cerebral arteries.

DOI： 10.1161/01.STR.0000259887.70358.e0

Combined use of TruFill DCS detachable coil system and Guglielmi detachable coil for embolization of meningioma fed by branches of the cavernous internal carotid artery - Technical case report

Noboru Kusaka, Takashi Tamiya, Kenji Sugiu, Koji Tokunaga, Mitsuhisa Nishiguchi, Kazuhiro Takayama, Yasuhiko Maeda, Kotaro Ogihara, Minoru Nakagawa, Tsukasa Nishiura

NEUROLOGIA MEDICO-CHIRURGICA 47 ( 1 ) 29 - 31 2007年1月

記述言語：英語出版者・発行元：JAPAN NEUROSURGICAL SOC

A 57-year-old female presented with a left petroclival meningioma fed by the meningohypophyseal trunk of the internal carotid artery (ICA). The enlarged tentorial marginal artery and inferior hypophyseal artery were successfully embolized with the TruFill DCS Detachable Coil System through a 0.019-inch inner diameter microcatheter. Superselective catheterization into the dorsal meningeal artery could not be achieved with the same microcatheter, because the catheter tip was too large to pass into the vessel. Subsequently the feeding artery was successfully embolized with a Guglielmi detachable coil (GDC) through a 0.016-inch inner diameter microcatheter. The patient underwent surgery without blood loss on the day after embolization. Our subjective impression was that the TruFill DCS was softer and had less resistance during insertion, whereas the GDC could be delivered through a smaller caliber system for smaller vessels. Appropriate use of the TruFill DCS and GDCs can allow efficient embolization of the feeding branches of the ICA.

DOI： 10.2176/nmc.47.29