Researchers Database

kusaka gen

    ComprehensiveMedicine2 Professor
Last Updated :2022/01/13

Researcher Information


J-Global ID

Research Interests

  • 脳血液関門   くも膜下出血   MAPK   ストレス蛋白   スタチン   VEGF   脳浮腫   脳・神経   急性期脳損傷   シグナル伝達   

Research Areas

  • Life sciences / Neurosurgery

Academic & Professional Experience

  • 2011  Jichi Medical UniversitySchool of Medicine准教授

Published Papers

  • Kamochi H, Kusaka G, Ishikawa M, Ishikawa S, Tanaka Y
    Neurologia medico-chirurgica 4 53 217 - 220 0470-8105 2013 [Refereed][Not invited]
  • Takeharu Kanazawa, Yusuke Watanabe, Mariko Hara, Akihiro Shinnabe, Gen Kusaka, Takanori Murayama, Yukiko Iino
    AMERICAN JOURNAL OF OTOLARYNGOLOGY 33 (3) 303 - 307 0196-0709 2012/05 [Refereed][Not invited]
    Purpose: Laryngeal framework surgery is usually performed under local anesthesia but cannot be tolerated by some patients. To develop a new procedure for these patients, we evaluated voice outcomes after arytenoid adduction combined with medialization laryngoplasty under general anesthesia using a laryngeal mask airway (LMA) for unilateral vocal cord paralysis. Materials and Methods: Eleven consecutive patients with severe unilateral vocal cord paralysis, with a maximum phonation time of less than 5 seconds, underwent arytenoid adduction combined with medialization laryngoplasty under general anesthesia using an LMA. Each paralyzed vocal cord was observed by intraoperative videolaryngoscopy. The vocal cord was moved to the position where the best vocal outcome could be expected, according to 3 parameters obtained from glottal images. Results: All patients achieved a maximum phonation time of more than 11 seconds. The mean airflow rate, which ranged from 550 to 1000 mL/s before surgery, improved to less than 390 mL/s. Perceptual evaluation using the grade, roughness, breathiness, asthenia and strain scale also improved significantly. Conclusions: These results were equivalent to those of previous reports of surgeries performed under local anesthesia. Intraoperative endoscopic vocal cord observation through the LMA may have contributed to the positive results. (C) 2012 Elsevier Inc. All rights reserved.
  • Kanazawa T, Sarukawa S, Fukushima H, Takeoda S, Kusaka G, Ichimura K
    Annals of vascular diseases 3 4 189 - 195 1881-641X 2011 [Refereed][Not invited]
  • Mami Ishikawa, Gen Kusaka, Kouichi Takashima, Haruna Kamochi, Soji Shinoda
    JOURNAL OF CLINICAL NEUROSCIENCE 17 (8) 1053 - 1056 0967-5868 2010/08 [Refereed][Not invited]
    A 54-year-old man presented with an intracranial schwannoma of the hypoglossal nerve between the medulla and the left hypoglossal canal. The condylar fossa approach was used with intra-operative electromyography (EMG) monitoring of the lower cranial nerves. The tumor was then removed carefully without decreasing the tongue EMG responses. EMG monitoring enabled us to remove the tumor while maintaining the function of the hypoglossal nerve. Tongue EMG was easily recorded by stimulating the hypoglossal nerve fibers, which was useful in identifying the hypoglossal nerve and evaluating its function. This suggests that tongue EMG is a useful monitoring tool to enhance neurological outcome following removal of tumors in this region. (C) 2009 Elsevier Ltd. All rights reserved.
  • Mami Ishikawa, Koichi Takashima, Haruna Kamochi, Gen Kusaka, Sohji Shinoda, Eiju Watanabe
    NEUROLOGICAL RESEARCH 32 (6) 656 - 660 0161-6412 2010/07 [Refereed][Not invited]
    Botulinum toxin type A (BTX) injection into the orbicularis oculi muscle is an effective treatment for patients with hemifacial spasm (HFS). The objectives of this study were to investigate the effect of this treatment on HFS, in particular the associated hyperexcitability of the facial motor nucleus, and to discuss the potential mechanism of HFS. F waves in the mentalis muscle were examined before, 2 and 6 weeks after the BTX treatment of only the orbicularis oculi muscle in ten patients with HFS. F/M ratio, duration of F waves and frequency of F waves decreased significantly after the BTX treatment compared with those before the BTX treatment. These findings demonstrate that the excitability of the facial motonucleus decreases after BTX treatment of the orbicularis oculi muscle. From these results, we hypothesize that the trigeminal afferent input and the cortical control contribute to the hyperexcitability of the facial motor nucleus in patients with HFS. This warrants further investigation into the pathophysiology of HFS.
  • Mami Ishikawa, Gen Kusaka, Kouichi Takashima, Haruna Kamochi, Soji Shinoda
    CLINICAL NEUROLOGY AND NEUROSURGERY 112 (5) 450 - 453 0303-8467 2010/06 [Refereed][Not invited]
    Under an operative view, an aneurysm of the vertebral artery is located behind the lower cranial nerves. To prevent neurological deficits we employed electrophysiological monitoring while clipping an aneurysm of the vertebral artery. A 64-year-old woman had suffered a sudden severe headache in the morning. Computed tomography (CT) revealed a subarachnoid hemorrhage (SAH) and CT angiography revealed an aneurysm at a branching point of the left vertebral artery. The condylar fossa approach was taken while recording electromyography (EMG) of the lower cranial nerves. The aneurysm was located just behind the hypoglossal nerve and could not be clipped without strong traction of the hypoglossal nerve. Therefore, the hypoglossal nerve was divided to separate the lower two bundles of the hypoglossal nerve from the other bundles, and the clip was applied to the aneurysm between the nerve bundles without any change of the tongue EMG. The patient went home 10 days after operation with no neurological deficit. In conclusion, we report a case of a ruptured aneurysm of a vertebral artery, which was clipped while monitoring the lower cranial nerves. Tongue EMG monitoring enabled us to clip the aneurysm without nerve injury and revealed that the hypoglossal nerve near the hypoglossal canal can be divided into several bands without neurological deficit. (C) 2010 Elsevier B.V. All rights reserved.
  • Mami Ishikawa, Gen Kusaka, Noriyuki Yamaguchi, Eiichi Sekizuka, Hiromichi Nakadate, Haruyuki Minamitani, Soji Shinoda, Eiju Watanabe
    NEUROSURGERY 64 (3) 546 - 553 0148-396X 2009/03 [Refereed][Not invited]
    OBJECTIVE: Pathophysiology after subarachnoid hemorrhage (SAH) caused by aneurysmal rupture has not been well examined. The purpose of this study was to observe platelet-leukocyte-endothelial cell interactions as indexes of inflammatory and prothrombogenic responses in the acute phase of SAH, using an in vivo cranial window method. METHODS: Subarachnoid hemorrhage was induced in C57Bl/6j mice by using the endovascular perforation method. Intravital microscopy was used to monitor the rolling and adhesion of platelets and leukocytes that were labeled with different fluorochromes. Regional cerebral blood flow was measured with laser Doppler flowmetry. The platelet-leukocyte-endothelial cell interactions were observed 30 minutes, 2 hours, and 8 hours after SAH. The effect of P-selectin antibody and apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase, on these responses was examined at 2 hours after SAH, and compared with a different SAH model in which autologous blood was injected into the foramen magna. RESULTS: SAH was accompanied by a 60% decrease in regional cerebral blood flow, whereas no changes in regional cerebral blood flow were observed on the contralateral side. SAH elicited time- and size-dependent increases in rolling and adherent platelets and leukocytes in cerebral venules. All of these interactions were attenuated by treatment with a P-selectin antibody or apocynin. There was no significant blood cell recruitment observed in the blood-injected SAH model. CONCLUSION: SAH at the skull base induced P-selectin- and oxygen radical-mediated platelet-leukocyte-endothelial cell interactions in venules at the cerebral surface. These early inflammatory and prothrombogenic responses may cause a whole-brain injury immediately after SAH.
  • Takashima K, Takahashi M, Yubune N, Inaba N, Omoto K, Kawano M, Sakurabayashi I, Ishikawa M, Kusaka G, Shinoda S
    Rinsho byori. The Japanese journal of clinical pathology 6 56 475 - 485 0047-1860 2008/06 [Refereed][Not invited]
  • Tomoyuki Saito, Yasutaka Watanabe, Miho Yuzawa, Takako Saito, Hiroyuki Tamemoto, Hisashi Suzuki, Gen Kusaka, Yoshio Omori, Soji Shinoda, Masanobu Kawakami, San-e Ishikawa
    INTERNAL MEDICINE 46 (10) 653 - 656 0918-2918 2007 [Refereed][Not invited]
    A 50-year-old man was admitted to determine the pathogenesis of hyponatremia. He had a poor appetite and was easily fatigued. Physical findings showed that he was conscious and alert. He had neither dry skin or tongue, nor pretibial edema. Laboratory data revealed that the serum sodium level was 110 mmol/l; plasma osmolality, 238 mmol/kg; and urinary osmolality, 417 mmol/kg. Plasma arginine vasopressin was 0.5 pg/ml despite plasma osmolality of 242 mmol/ kg. An acute water load showed impaired water excretion, as percent excretion of water load was 30% and minimal urinary osmolality was 642 mmol/kg. Serum prolactin was 254 ng/ml, and anterior pituitary hormones of ACTH, TSH and GH were in the normal ranges. Brain magnetic resonance imaging (MRI) showed a pituitary tumor with a size of 20 x 22 x 21 mm and it pushed a pituitary stalk upward. Immunohistochemistry revealed prolactinoma. After the adenomectomy, serum sodium level has been kept normal with free access to water intake. The present study indicates that syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is manifested in association with pituitary macroadenoma of prolactinoma.
  • M Yamaguchi, JW Calvert, G Kusaka, JH Zhang
    STROKE 36 (10) 2212 - 2214 0039-2499 2005/10 [Refereed][Not invited]
    Background and Purpose-We report a modified 4-vessel occlusion (4VO) rat model. Method-We used a 1-stage anterior approach for making bilateral hemispheric ischemia. Results-Modified 4VO method decreased cerebral blood flow to 12% to 14% of baseline levels. Conclusion-This modified 4VO method is a minimally invasive, quick, reliable procedure for producing ischemic changes.
  • Patwardhan RV, Calvert JW, Besio W, Kusaka G, Kusaka I, Zhang J, Nanda A
    Frontiers in bioscience : a journal and virtual library 10 3009 - 3012 1093-9946 2005/09 [Refereed][Not invited]
  • Patwardhan RV, Besio W, Calvert JW, Kusaka G, Kusaka I, Zhang J, Nanda A
    Frontiers in bioscience : a journal and virtual library 10 3013 - 3019 1093-9946 2005/09 [Refereed][Not invited]
  • G Kusaka, T Ishikawa, A Nanda, TN Granger, JH Zhang
    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 24 (8) 916 - 925 0271-678X 2004/08 [Refereed][Not invited]
    Few studies have examined the signaling pathways that contribute to early brain injury after subarachnoid hemorrhage (SAH). Using a rat SAH model, the authors explored the role of vascular endothelial growth factor (VEGF) and mitogen-activation protein kinase (MAPK) in early brain injury. Male Sprague-Dawley rats (n = 172) weighing 300 to 350 g were used for the experimental SAH model, which was induced by puncturing the bifurcation of the left anterior cerebral and middle cerebral arteries. The blood-brain barrier (BBB), brain edema, intracranial pressure, and mortality were evaluated at 24 hours after SAH. The phosphorylation of VEGF and different MAPK subgroups (ERK 1/2, p3 8, and JNK) were examined in both the cortex and the major cerebral arteries. Experimental SAH increased intracranial pressure, BBB permeability, and brain edema and produced high mortality. SAH induced phosphorylation of VEGF and MAPKs in the cerebral arteries and, to a lesser degree, in the cortex. PPI, an Src-family kinase inhibitor, reduced BBB permeability, brain edema, and mortality and decreased the phosphorylation of VEGF and MAPKs. The authors conclude that VEGF contributes to early brain injury after SAH by enhancing the activation of the MAPK pathways, and that the inhibition of these pathways might offer new treatment strategies for SAH.
  • Kusaka, I, G Kusaka, C Zhou, M Ishikawa, A Nanda, DN Granger, JH Zhang, JP Tang
    AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 286 (6) H2442 - H2451 0363-6135 2004/06 [Refereed][Not invited]
    The objective of the present study was to examine the role of the angiotensin II type 1 receptor (AT(1)-R) in the diabetes-aggravated oxidative stress and brain injury observed in a rat model of combined diabetes and focal cerebral ischemia. Diabetes was induced by an injection of streptozotoxin (STZ; 55 mg/kg iv) at 8 wk of age. Two weeks after the induction of diabetes, some animals received continuous subcutaneous infusion of the AT(1)-R antagonist candesartan (0.5 for 14 days. Focal cerebral ischemia, induced by middle cerebral artery occlusion/reperfusion (MCAO), was conducted at 4 wk after STZ injection. Male Sprague-Dawley rats (n = 189) were divided into five groups: normal control, diabetes, MCAO, diabetes + MCAO, and diabetes + MCAO + candesartan. The major observations were that 1) MCAO produced typical cerebral infarction and neurological deficits at 24 h that were accompanied by elevation of NAD(P)H oxidase gp91(phox) and p22(phox) mRNAs, and lipid hydroperoxide production in the ipsilateral hemisphere; 2) diabetes enhanced NAD( P) H oxidase gp91phox and p22phox mRNA expression, potentiated lipid peroxidation, aggravated neurological deficits, and enlarged cerebral infarction; and 3) candesartan reduced the expression of gp91phox and p22phox, decreased lipid peroxidation, lessened cerebral infarction, and improved the neurological outcome. We conclude that diabetes exaggerates the oxidative stress, NAD( P) H oxidase induction, and brain injury induced by focal cerebral ischemia. The diabetes-aggravated brain injury involves AT(1)-Rs. We have shown for the first time that candesartan reduces brain injury in a combined model of diabetes and cerebral ischemia.
  • G Kusaka, JW Calvert, C Smelley, A Nanda, JH Zhang
    JOURNAL OF NEUROSCIENCE METHODS 135 (1-2) 121 - 127 0165-0270 2004/05 [Refereed][Not invited]
    Objective: Monitoring cerebrospinal fluid pressure or intracranial pressure (ICP) is crucial in the study of neurosurgical disorders. In the present study. we report a new lumbar method for monitoring ICP in rats. Methods: A PE10 catheter connected to a pressure transducer was placed into the subarachnoid space of L5 through the duramater after laminectomy to record lumbar cerebrospinal fluid pressure (lumbar-ICP). ICP at the cisterna magna (cistema-ICP) was recorded simultaneously via a catheter in the subarachnoid space at the cisterna magna. Eighteen anesthetized adult male S-D rats were subjected to baseline recording followed by either experimental subarachnoid hemorrhage (SAH) induced by intravascular puncture method or experimental intracerebral hemorrhage (ICH) induced by blood injection with a stereotaxic system. Results.. Baseline lurnbar-ICP and cisterna-ICP varied between 6 and 8 mmHg, and respiratory variation could be detected. A similar acute response to SAH was recorded in both the lumbar-ICP and cisterna-ICP in all rats. In rats Subjected to SAH, the lumbar catheter continuously and accurately monitored lumbar-ICP and reliable pressure tracings were obtained for up to 24 It after SAH. However, continued cistema-ICP monitoring was abandoned in two rats in the cisterna magna method due to obstruction of the catheter by blood clots (hematoma). Conclusion: This new lumbar-ICP method is simple, safe, easy. and reliable in rats. Continued lumbar-ICP measurements provided monitoring, for up to 24 h after experimental manipulation. (C) 2003 Elsevier B.V. All rights reserved.
  • CM Zhou, M Yamaguchi, G Kusaka, C Schonholz, A Nanda, JH Zhang
    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 24 (4) 419 - 431 0271-678X 2004/04 [Refereed][Not invited]
    Apoptosis in the endothelium of major cerebral arteries may play a role in the initiation and maintenance of cerebral vasospasm after subarachnoid hemorrhage (SAH). We tested the therapeutic effect of caspase inhibitors on endothelial apoptosis and on cerebral vasospasm in an established dog double-hemorrhage model. Thirty-one mongrel dogs were divided into five groups: control; SAH; SAH treated with vehicle [DMSO]; SAH treated with Ac-DEVD-CHO [a specific caspase-3 inhibitor] and SAH treated with Z-VAD-FMK [a broad caspase inhibitor]. The inhibitors (100 muM) were injected into the cisterna magna daily front Day 0 through Day 3. Angiography was performed on Day 0 and Day 7. Histology, TUNEL staining, and immunohistochemistry were conducted on basilar arteries collected on Day 7 after SAH. Positive staining of TUNEL, poly(ADP)-ribose polymerase (PARP), caspase-3, and caspase-8 was observed in the endothelial cells of the spastic arteries. Double fluorescence labeling demonstrated colocalization of TUNEL with caspase-3 and TNFalpha-receptor-1 (TNFR I). Ac-DEVD-CHO and Z-VAD-FMK prevented endothelial apoptosis and reduced angiographic vasospasm. The mechanism of apoptosis in endothelial cells involves TNFR1 and the caspase-8 and caspase-3 pathways. Caspase inhibitors may have potential in the treatment of cerebral vasospasm..
  • G Kusaka, H Kimura, Kusaka, I, E Perkins, A Nanda, JH Zhang
    JOURNAL OF NEUROSURGERY 99 (2) 383 - 390 0022-3085 2003/08 [Refereed][Not invited]
    Object. Mitogen-activated protein kinase (MAPK) has been implicated in cerebral vasospasm after subarachnoid hemorrhage (SAH). This study was conducted to investigate whether Src tyrosine kinase, an upstream regulator of MAPK, is involved in cerebral vasospasm. Methods. An established canine double-hemorrhage model was used. Twenty-four dogs were divided into four groups: control, vehicle-treated, Src inhibitor PP2-treated, and Src inhibitor damnacanthal-treated groups. Vehicle (dimethyl sulfoxide), PP2, or damnacanthal was injected daily into the cisterna magna of IS dogs at 3 to 6 days after induction of SAH. Angiography was performed on Day 0 (the day on which the first blood injection was administered to induce SAH) and on Day 7. Western blot analysis of Src and MAPK activation in basilar arteries (BAs) collected on Day 7 post-SAH was performed. Severe vasospasm was observed in the BAs of vehicle-treated dogs. Mild vasospasm was observed in all dogs treated with Src inhibitors. Phosphorylated Src and MAPK were increased after SAH and activation of these kinases in the BAs was abolished by PP2 and damnacanthal. Conclusions. The tyrosine kinase Src is an important upstream regulator of MAPK, and inhibition of Src might offer a new therapy in the management of cerebral vasospasm.


  • ISHIKAWA Mami, KUSAKA Gen, SHINODA Soji, YAMAGUCHI Noriyuki, WATANABE Eiju  脳卒中の外科 = Surgery for cerebral stroke  37-  (2)  93  -99  2009/03  [Not refereed][Not invited]
  • TAKASHIMA Kouichi, TAKAHASHI Mayumi, YUBUNE Norio, INABA Nobuo, OMOTO Kiyoka, KAWANO Mikihiko, SAKURABAYASHI Ikunosuke, ISHIKAWA Mami, KUSAKA Gen, SHINODA Souji  The Official journal of Japanese Society of Laboratory Medicine  56-  (6)  475  -485  2008/06  [Not refereed][Not invited]
  • Suzuki Hisashi, Kusaka Gen, Omori Yoshio, Shinoda Soji  Jichi Medical University journal  29-  181  -186  2006/12  [Not refereed][Not invited]
    Although pituitary apoplexy associated with Rathke's cleft cyst is rare, we have experienced two cases. A28-year-old man had sudden onset of headache, nausea, and vertigo in March 2004. Brain magnetic resonance imaging (MRI) revealed a pituitary fossa mass with suspected intratumoral bleeding. The mass was surgically removed using a trans-sphenoidal approach. The pathological findings indicated Rathke's cleft cyst. The other case was a 32-year-old woman who developed headache in September 2004. Brain MRI showed intratumoral bleeding at a pituitary lesion mass. The trans-sphenoidal approach was again used to remove the tumor and hematoma. The microscopic findings of Rathke's cleft cyst were almost identical to those of the first case. Symptoms resolved postoperatively in both patients. Although pituitary apoplexy is usually caused by pituitary adenoma, Rathke's cleft cyst should be considered in the differential diagnosis.
  • 鈴木 尚, 神田 大, 草鹿 元, 大森 義男, 石川 三衛, 篠田 宗次  日本内分泌学会雑誌  81-  164  -165  2005/09  [Not refereed][Not invited]
  • T. Miyawaki, G. Kusaka, S. Shinoda, T. Masuzawa  Japanese Journal of Neurosurgery  10-  (6)  409  -413  2001  [Not refereed][Not invited]
    Primary involvement of the spinal cord in malignant lymphoma is uncommon, with only 22 cases having been confirmed in the literature. We describe a 41-year-old man with symptoms attributable to spinal cord lesion. The presenting sympton was spastic paresis and dysesthesia of the lower extremities, followed by urinary incontinence. Radiological examinations, including magnetic resonance imaging (MRI) with gadolinium (Gd-DTPA), revealed an intramedullary tumor at the levels of Th7-9. Laminectomy was performed with direct examination of the spinal cord at the levels of Th8-9. A biopsy specimen was obtained, and pathological examination revealed non-Hodgkin malignant lymphoma with B-cell surface marker. Radiation therapy was administered to the spinal lesion at the levels of Th4-12. The total dose was 40 Gy. Result of physical examination gradually improved, and MRI with Gd-DTPA showed no residual tumor. In addition to this case report, we review the literature on primary lymphomas of primary spinal intramedullary malignant lymphoma.
  • Nagai Mutsumi, Oguro Keiji, Kusaka Gen, Shinoda Souji, Masuzawa Toshio  Spinal surgery : official journal of the Japanese Society of Spinal Surgery  12-  (1)  57  -62  1998/03  [Not refereed][Not invited]
    A case of cervical spinal enterogenous cyst is reported. A 33-year-old woman visited the hospital. Sensory examination showed slight diminution of sensation to pinprick on her right side up to the C4 dermatomere level. Magnetic resonance (MR) imaging revealed an intradural cystic mass located on the ventral side at the C5 level of the cervical vertebra. We removed the cyst totally, with laminectomy of C4-6 and right side partial facetectomy of C4/5 and C5/6. The cyst was composed of an epithelial layer and connective tissue, and was only slightly stained for periodic acid-Schiff. The cyst wall had no goblet cells at all. Electron microscopic findings revealed ciliated cells, non-ciliated cells and basal cell-like cells, which showed no evidence of mucin secretion. Although the cyst was lacking in one of the characteristics of enterogenous cyst, namely, mucin secretion, we still diagnosed it as an enterogenous cyst because the cyst wall was similar to bronchiolar epithelium and showed only endodermal elements. To our knowledge, an enterogenous cyst like the one in our case is very rare.

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