Name of Division: Neurosurgery

Overview

Department of neurosurgery at Tokyo Medical and Dental University has been providing outstanding care to patients with surgically treatable neurological diseases, such as brain and spinal cord tumors, cerebrovascular disease, trigeminal neuralgia, and intractable epilepsy. Our other goals include the education of undergraduates and residents, and research activities to improve the outcome of diverse neurosurgical illnesses.

Staff

Education

　　Undergraduate Course

　The students take the lectures featuring neuroanatomy, neurology, neurophysiology, neuroradiology, and a variety of neurological diseases. After receiving a neurosurgery introductory course in a small group, they take a clinic-based program called bed-side learning (BSL), where every student is expected to participate in a team to manage patients.

　　Residency Program

　We provide the most advanced training to neurosurgery residents which helps them acquire the certified board of The Japan Neurosurgical Society.
　Year 1, Training for the basic clinical neurosurgery at the University Hospital.
　Year 2, Training for the basic clinical neurosurgery at one of the affiliated hospitals.
　Year 3-6, Continuing training for clinical neurosurgery, and basic or clinical research in neurosurgery.

　

Research Subjects

　We perform research in a wide variety of neurosurgical fields with the aim of improving the status of patients. To achieve this, we build interdisciplinary research projects that enable us to introduce and develop innovative tools and techniques.

　 1. Neuro-Oncology

1-1) Neurosurgical operation of gliomas using pre-and intraoperative functional brain mapping, including PET and optical imaging

1-2) Analysis of the mechanisms of tumor growth and invasion, and its application to the treatment of glial tumors. The topics include cell cycle, growth factors, invasive phenotype, and tumor angiogenesis.

1-3) Analysis of the roles for tumor suppressor genes and oncogenes in gliomas, meningiomas, and neurofibromatosis type 2. Development of a novel gene therapy approach to these diseases based on the findings.

1-4) Development of adjunctive treatment modalities including photodynamic therapy, irradiation, chemotherapeutics, immunotherapy, and anti-angiogenesis.

1-5) Development of novel gene therapy strategies against malignant brain tumors including cytokine-gene based immunogene therapy and the use of replication-selective oncolytic herpes simplex viruses.

1-6) Development of new imaging for glioma using PET amino acid tracer, persusion MRI and CT.

2. Cerebrovascular diseases

2-1) Analysis of the mechanisms of vasospasm that follows subarachnoid hemorrhage, and its application to the treatment. Studies on the cerebral hemodynamics and vasoreactivities. Investigations on the possible involvement of endothelin, free radicals, nitric oxide, and fibrinolysis.

2-2) Analysis of the impaired cerebral circulation in ischemic as well as hemorrhagic cerebrovascular diseases, focusing on the neuronal plasticity.

2-3) Studies on the pathology of "Moyamoya disease" and an asssessment of the efficacy of indirect extracranial-intracranial arterial anastomosis surgery.

3. Neurotrauma

3-1) Analysis of neuronal toxicity and plasticity through dynamic simulation of cerebro-spinal injury.

3-2) Experimental studies to develop a novel approach to treat neurotrauma.

3-3) Clinical studies to analyze the pathophysiology of diffuse brain injury using functional brain imaging.

4. Functional neurological diseases

4-1) Analysis of the pathology of temporal lobe epilepsy and development of a safe and effective surgical technique.

4-2) Investigations on neurotransmittors.

5. Cerebral circulation,metabolism and function

5-1) Multimodal clinical and experimental studies on human cerbral blood flow, metabolism and function using positron emission tomography (PET), MRI/S, magnetic encephelography (MEG) and optical imaging.

5-2) Investigations on neuronal receptors in diseased brain using PET.

5-3) Application of optical imaging to intraoperative brain mapping and to the analysis of human brain specimen.

Publications (since 2000)

　Abe T, Wakimoto H, Bookstein R, Maneval DC, Chiocca EA, Basilion JP. Intra-arterial delivery of p53-containing adenoviral vector into experimental brain tumors. Cancer Gene Ther. 9:228-35, 2002.

　Maehara T, Shimizu H, Kawai K, Shigetomo R, Tamagawa K, Yamada T, Inoue M. Postoperative development of children after hemispherotomy. Brain Dev. 24:155-60, 2002.

　Mizuno Y, Azuma H, Ito Y, Isotani E, Ohno K, Hirakawa K. Inhibitory effect of activated protein C on cerebral vasospasm after subarachnoid hemorrhage in the rabbit. J Cardiovasc Pharmacol. 39:729-38, 2002.

　Saigusa K, Takei H, Shishido T, Ohki J, Naoe N, Ohno K. [Benign intracranial hypertension resulting from corticosteroid withdrawal: case report] No Shinkei Geka. 30:57-62, 2002.

　Sato K, Nariai T, Sasaki S, Yazawa I, Mochida H, Miyakawa N, Momose-Sato Y, Kamino K, Ohta Y, Hirakawa K, Ohno K.Intraoperative intrinsic optical imaging of neuronal activity from subdivisions of the human primary somatosensory cortex. Cereb Cortex 12:269-80, 2002.

　Shimada Y, Ishiwata K, Kiyosawa M, Nariai T, Oda K, Toyama H, Suzuki F, Ono K, Senda M. Mapping adenosine A(1) receptors in the cat brain by positron emission tomography with [11C]MPDX. Nucl Med Biol. 2002;29:29-37

　Takaishi Y, Hashimoto K, Fujino O, Arai N, Mizuguchi M, Maehara T, Shimizu H. [A case of intractable epilepsy: diagnosis of tuberous sclerosis based on histopathological findings and immunohistochemical expression of hamartin and tuberin] No To Hattatsu. 34:49-54, 2002.

　Toriyama H, Wang L, Saegusa H, Zong S, Osanai M, Murakoshi T, Noda T, Ohno K, Tanabe T. Role of Ca(v) 2.3 (alpha1E ) Ca2+ channel in ischemic neuronal injury. Neuroreport. 13:261-5, 2002.

　Wakimoto H, Ikeda K, Abe T, Ichikawa T, Hochberg FH, Ezekowitz RA, Pasternack MS, Chiocca EA. The complement response against an oncolytic virus is species-specific in its activation pathways. Mol Ther. 5:275-82, 2002.

　Wu H, Kanatous SB, Thurmond FA, Gallardo T, Isotani E, Bassel-Duby R, Williams RS. Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science. 296:349-52, 2002.

　Yamamoto S, Ohno K, Aoyagi M, Ichinose S, Hirakawa K. Calcific deposits on degraded shunt catheters: long-term follow-up of V-P shunts and late complications in three cases. Childs Nerv Syst. 18:19-25, 2002.

　Yamamoto S, Yoshida Y, Aoyagi M, Ohno K, Hirakawa K, Hamada H. Reduced Transduction Efficiency of Adenoviral Vectors Expressing Human p53 Gene by Repeated Transduction into Glioma Cells in Vitro. Clin Cancer Res. 8:913-21, 2002.

　Duan L, Aoyagi M, Tamaki M, Nakagawa K, Nagashima G, Nagasaka Y, Ohno K, Yamamoto K, Hirakawa K. Sensitization of human malignant glioma cell lines to tumor necrosis factor-induced apoptosis by cisplatin. J Neurooncol. 52:23-36, 2001.

　Grange RW, Isotani E, Lau KS, Kamm KE, Huang PL, Stull JT. Nitric oxide contributes to vascular smooth muscle relaxation in contracting fast-twitch muscles. Physiol Genomics. 5:35-44, 2001.

　Hayakawa T, Chang MC, Rapoport SI, Appel NM.. Selective dopamine receptor stimulation differentially affects [3H]arachidonic acid incorporation, a surrogate marker for phospholipase A2-mediated neurotransmitter signal transduction, in a rodent model of Parkinson's disease. J Pharmacol Exp Ther. 296:1074-84, 2001.

　Komaki H, Sugai K, Maehara T, Shimizu H. Surgical treatment of early-infantile epileptic encephalopathy with suppression-bursts associated with focal cortical dysplasia. Brain Dev. 23:727-31, 2001.

　Masaoka H, Takasato Y, Nojiri T, Hayakawa T, Akimoto H, Yatsushige H, Toumori H, Miyazaki Y, Honma M. Clinical effect of Fasudil hydrochloride for cerebral vasospasm following subarachnoid hemorrhage. Acta Neurochir Suppl. 77:209-11, 2001.

　Maehara T, Shimizu H. Surgical outcome of corpus callosotomy in patients with drop attacks. Epilepsia. 42:67-71, 2001.

　Nagashima G, Aoyagi M, Yamamoto S, Wakimoto H, Tamaki M, Yamamoto K, Fujimoto T, Hirakawa K. Involvement of disregulated c-myc but not c-sis/PDGF in atypical and anaplastic meningiomas. Clin Neurol Neurosurg. 103:13-8, 2001.

　Nakane M, Tamura A, Miyasaka N, Nagaoka T, Kuroiwa T. Astrocytic swelling in the ipsilateral substantia nigra after occlusion of the middle cerebral artery in rats. AJNR Am J Neuroradiol. 22:660-3, 2001.

　Nariai T, Suzuki R, Ohta Y, Ohno K, Hirakawa K. Focal cerebral hyperemia in postconcussive amnesia. J Neurotrauma 18:1323-32, 2001.

　Nariai T, Ohno K, Ohta Y, Hirakawa K, Ishii K, Senda M. Discordance between cerebral oxygen and glucose metabolism, and hemodynamics in a mitochondrial encephalomyopathy, lactic acidosis, and strokelike episode patient. J Neuroimaging 11:325-9, 2001.

　Obayashi S, Suhara T, Kawabe K, Okauchi T, Maeda J, Akine Y, Onoe H, Iriki A. Functional brain mapping of monkey tool use. Neuroimage. 14:853-61, 2001.

　Ohta Y, Nariai T, Akimoto H, Shimohira M, Sugimoto J, Ohno K, Senda M, Hirakawa K. Tuberous sclerosis: epileptogenicity and multimodal presurgical evaluations. Childs Nerv Syst 17:313-9, 2001.

　Saegusa H, Kurihara T, Zong S, Kazuno A, Matsuda Y, Nonaka T, Han W, Toriyama H, Tanabe T. Suppression of inflammatory and neuropathic pain symptoms in mice lacking the N-type Ca2+ channel. EMBO J. 20:2349-56, 2001.

　Shimizu T, Maehara T, Hino T, Komori T, Shimizu H, Yagishita A, Yokota T, Hirai S, Rossini PM. Effect of multiple subpial transection on motor cortical excitability in cortical dysgenesis. Brain. 124:1336-49, 2001.

　Takada Y, Morimoto T, Sugawara T, Ohno K. Trigeminal neuralgia associated with achondroplasia. Case report with literature review. Acta Neurochir (Wien). 143:1173-6, 2001.

　Uchida S, Maehara T, Hirai N, Okubo Y, Shimizu H. Cortical oscillations in human medial temporal lobe during wakefulness and all-night sleep. Brain Res. 891:7-19, 2001.

　Yamada I, Nakagawa T, Matsushima Y, Shibuya H. High-resolution turbo magnetic resonance angiography for diagnosis of Moyamoya disease. Stroke. 32:1825-31, 2001.

　Zhao F, Kuroiwa T, Miyasaka N, Nagaoka T, Nakane M, Tamura A, Mizusawa H. Characteristic changes in T(2)-value, apparent diffusion coefficient, and ultrastructure of substantia nigra evolving exofocal postischemic neuronal death in rats. Brain Res. 895:238-44. 2001.

　Ikeda K, Wakimoto H, Ichikawa T, Jhung S, Hochberg FH, Louis DN, Chiocca EA. Complement depletion facilitates the infection of multiple brain tumors by an intravascular, replication-conditional herpes simplex virus mutant. J Virol 74:4765-75, 2000.

　Ishiwata K, Noguchi J, Wakabayashi S, Shimada J, Ogi N, Nariai T, Tanaka A, Endo K, Suzuki F, Senda M. 11C-labeled KF18446: a potential central nervous system adenosine A2a receptor ligand. J Nucl Med 41: 345-54, 2000.

　Ito Y, Isotani E, Mizuno Y, Azuma H, Hirakawa K. Effective improvement of the cerebral vasospasm after subarachnoid hemorrhage with low-dose nitroglycerin. J Cardiovasc Pharmacol 35:45-50, 2000.

　Jiang XB, Ohno K, Tominaga B, Lian Q, Kuroiwa T, Nariai T, Hirakawa K. Changes in local cerebral blood flow, glucose utilization, and mitochondrial function following traumatic brain injury in rats. Neurol Med Chir 40: 16-29, 2000.

　Kuroiwa T, Nagaoka T, Miyasaka N, Akimoto H, Zhao F, Yamada I, Ueki M, Ichinose S. Time course of trace of diffusion tensor [Trace(D)] and histology in brain edema. Acta Neurochir Suppl. 76:191-4, 2000.

　Lau KS, Grange RW, Isotani E, Sarelius IH, Kamm KE, Huang PL, Stull JT. nNOS and eNOS modulate cGMP formation and vascular response in contracting fast-twitch skeletal muscle. Physiol Genomics, 2:21-7, 2000.

　Maehara T, Arai N, Shimizu H, Yagishita A, Oda M. Cortical dysplasia with ossification. Epilepsia 41:1489-1493, 2000.

　Masaoka H, Takasato Y, Hayakawa T, Yatsushige H, Kamisasa H, Sumiyoshi K, Homma M. Cerebral blood flow measurement of severely head-injured patients during mild hypothermia. Keio J Med. 49 Suppl 1:A159-60, 2000.

　Mishina M, Senda M, Kimura Y, Toyama H, Ishiwata K, Ohyama M, Nariai T, Ishii K, Oda K, Sasaki T, Kitamura S, Katayama Y. Intrasubject correlation between static scan and distribution volume images for [11C]flumazenil PET. Ann Nucl Med 14:193-198, 2000.

　Miyasaka N, Kuroiwa T, Zhao FY, Nagaoka T, Akimoto H, Yamada I, Kubota T, Aso T. Cerebral ischemic hypoxia: discrepancy between apparent diffusion coefficients and histologic changes in rats. Radiology. 215:199-204, 2000.

　Miyasaka N, Nagaoka T, Kuroiwa T, Akimoto H, Haku T, Kubota T, Aso T. Histopathologic correlates of temporal diffusion changes in a rat model of cerebral hypoxia/ischemia. AJNR Am J Neuroradiol. 21:60-6, 2000.

　Nakagawa K, Hirai K, Aoyagi M, Yamamoto K, Hirakawa K, Katayama Y. Bloody cerebrospinal fluid from patients with subarachniod hemorrhage alters intracellular calcium regulations in cultured human vascular endothelial cells. Neurol Res 22:588-596, 2000.

　Nakagawa K, Touho H, Morisako T, Osaka Y, Tatsuzawa K, Nakae H, Owada K, Matsuda K, Karasawa J Long-term follow-up study of unruptured vertebral artery dissection: clinical outcomes and serial angiographic findings. J Neurosurg; 93:19-25, 2000.

　Nariai T, Ohno K, Akimoto H, Ohta Y, Nagaoka T, Hirakawa K, Ishii K, Senda M. Cerebral blood flow, vascular response and metabolism in patients with MELAS syndrome--xenon CT and PET study. Keio J Med 49 Suppl 1:A68-70, 2000.

　Obayashi S, Tanaka M, Iriki A. Subjective image of invisible hand coded by monkey intraparietal neurons. Neuroreport 11:3499-3505, 2000.

　Shimizu H, Maehara T. Modification of peri-insular hemispherotomy and surgical results. Neurosurgery 47:367-373, 2000.

　Shimizu T, Nariai T, Maehara T, Hino T, Komori T, Shimizu H, Hirai S, Senda M. Enhanced motor cortical excitability in the unaffected hemisphere after hemispherectomy. Neuro Report 11, 3077-3084, 2000.

　Shimizu H, Maehara T. Neuronal disconnection for the surgical treatment of pediatric epilepsy. Epilepsia. 41 Suppl 9:28-30, 2000.

　Someya Y, Obata T, Suhara T, Ota Y, Ikehira H, Tanada S, Hirakawa K, Okubo Y, Sasaki Y. Seizure frequency and bilateral temporal abnormalities: a proton magnetic resonance spectroscopy of temporal lobe epilepsy. Seizure9: 274-279, 2000.

　Uchida S, Nakayama H, Maehara T, Hirai N, Arakaki H, Nakamura M, Nakabayashi T, Shimizu H. Suppression of gamma activity in the human medial temporal lobe by sevoflurane anesthesia. Neuro Report 11, 39-42, 2000.

　Uesugi H, Shimizu H, Maehara T, Arai N, Nakayama H. Presence of humman herpesvirus 6 and herpes simplex virus detected by polymmerase chain reaction in surgical tissue from temporal lobe epileptic patients. Psychiat Clin Neuros 54, 589-593, 2000.

　Wakabayashi S, Nariai T, Ishiwata K, Nagaoka T, Hirakawa K, Oda K, Sakiyama Y, Shumiya S, Toyama H, Suzuki F, Senda M. A PET study of adenosine A1 receptor in anesthetized monkey brain. Nucl Med Biol 27:401-406, 2000.

　Yamada I, Himeno Y, Matsushima Y, Shibuya H. Renal artery lesions in patients with moyamoya disease: angiogrphic findings. Stroke 31: 733-737, 2000.

　Yamamoto M, Akazawa K, Aoyagi M, Yamamoto K Changes in biological characteristics during the cellular aging of ligament fibroblasts derived from patients with prolapse uteri. Mech Aging Dev 115:175-187, 2000.

　Yoshino Y, Aoki N, Oikawa A, Ohno K. Acute epidural hematoma developing during twist-drill craniostomy: a complication of percutaneous subdural tapping for the treatment of chronic subdural hematoma. Surg Neurol, 53:601-604, 2000.

　Matsushima Y: Moyamoya Diseaseﾓ in (Albright AL, Pollack IF, Adelson PD eds.) Operative Techniques in Pediatric Neurosurgery, Thieme, New York, 2001、pp 239-244

　Takasato Y, Masaoka H, Wakimoto H, Naoe N, Saigusa K, Nagai M, Kuramoto K. Combined Therapy of Local Intraarterial Thrombolysis and Brain Hypothermia for Acute Occlusion of the Cerebral Main Trunk Arteries Hayashi N (Ed.) Brain Hypothermia (Pathology, Pharmacology, and Treatment of Severe Brain Injury) Springer pp,187-193, 2000

　Toyama H, Takazawa K, Nariai T, Uemura K, Senda M, Visualization of correlated hemodynamic and metabolic functions in cerebrovascular disease by a cluster analysis with PET study., in Physiological imaging of the brain with PET, Gjedde A, et al., Editors. 2001, Academic Press: San Diego. p.301-304

　

[Graduate School, School of Medicine]

［TOKYO MEDICAL AND DENTAL UNIVERSITY］