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Toru Fujii, Toru Itakura, Seiji Hayashi, Norihiko Komai, Hirokazu Nakamine and Koji Saito

✓ A case of primary pineal choriocarcinoma with acute onset of hemorrhage is reported in a young male. The patient received conservative therapy, including irradiation, on the basis of a suspected germinoma. Subsequent serial computerized tomography showed progressive hemorrhage in the primary pineal choriocarcinoma, which was confirmed at autopsy.

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Taku Shigeno, Tatsuo Mima, Masashi Yanagisawa, Akira Saito, Katsutoshi Goto, Kazumasa Yamashita, Toshiharu Takenochi, Naosuke Matsuura, Yasuhide Yamasaki, Koji Yamada, Tomoh Masaki and Kimitomo Takakura

✓ The role of endothelin, a newly found vasoconstrictor peptide, is examined in the pathogenesis of cerebral vasospasm after experimental subarachnoid hemorrhage (SAH) in the dog. Endothelin immunoreactivity was overexpressed in the endothelium of the vasospastic basilar artery. Because endothelin synthesis is regulated at the messenger ribonucleic acid transcription level, the effect of actinomycin D, a ribonucleic acid synthesis inhibitor, was studied as a means of preventing vasospasm. It was found that treatment with intravenous actinomycin D for 5 days beginning on the day of SAH completely inhibited the development of vasospasm. This novel experimental therapy may lead not only to the elucidation of the pathogenesis of cerebral vasospasm but also to the availability of a prophylactic adjuvant therapy for patients with SAH.

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Hideaki Imai, Kenjiro Konno, Mitsunobu Nakamura, Tatsuya Shimizu, Chisato Kubota, Koji Seki, Fumiaki Honda, Shinichiro Tomizawa, Yukitaka Tanaka, Hidekazu Hata and Nobuhito Saito

Object

The purpose of this set of studies is to design a minimally invasive, reproducible stroke model in the gyrencephalic brain. This paper provides information on both surgical technique and methods of quantification of ischemic damage to both gray and white matter in the miniature pig.

Methods

Sixteen male miniature pigs were randomly divided into three groups and underwent transcranial surgery involving a frontotemporal approach with orbital rim osteotomy for permanent middle cerebral artery occlusion (MCAO; five animals), permanent internal carotid artery occlusion (ICAO; six animals), and a sham operation (five animals). Histological mapping and magnetic resonance (MR) imaging were used to delineate the areas of ischemic damage. The volumes of infarction measured directly from MR images were 16.2 ± 1.1, 1.5 ± 0.5, and 0.0 ± 0.0 cm3 (mean ± standard deviation [SD], p < 0.001) in the MCAO, ICAO, and sham-operated groups, respectively. The areas of ischemia identified through histological analysis and MR imaging showed a good correlation (r2 = 0.86, p < 0.0001). Immunohistochemical staining with an amyloid precursor protein (APP) antibody was used to evaluate axonal damage and calculate a total APP score for axonal damage of 44.8 ± 2.9 in the MCAO, 13.2 ± 6.6 in the ICAO, and 0.0 ± 0.0 (mean ± SD, p < 0.002) in the sham-operated animals.

Conclusions

This new model of focal cerebral ischemia induces a reproducible amount of ischemic damage in both gray and white matter, and has significant utility for studies of the pathophysiology of ischemia in the gyrencephalic brain and for assessment of the therapeutic efficacy of drugs prior to the initiation of human clinical trials.

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Mitsunobu Nakamura, Hideaki Imai, Kenjiro Konno, Chisato Kubota, Koji Seki, Sandra Puentes, Ahmad Faried, Hideaki Yokoo, Hidekazu Hata, Yuhei Yoshimoto and Nobuhito Saito

Object

Encephalomyosynangiosis (EMS) is a surgical treatment for moyamoya disease that is widely used to provide increased intracranial blood flow via revascularization by arterial anastomosis from the external carotid artery. However, the angiogenic mechanism responsible for the revascularization induced by EMS has not been systematically evaluated. In this study the authors investigated the chronological angiogenic changes associated with EMS to clarify the favorable factors and identify revascularization mechanisms by using an experimental internal carotid artery occlusion (ICAO) model in the miniature pig.

Methods

Fourteen miniature pigs were used, 11 of which underwent ICAO before transcranial surgery for EMS was performed. Animals were allowed to recover for 1 week (4 pigs) or 4 weeks (7 pigs) after EMS. Control group animals were treated in the same way, but without occlusion (3 pigs). Magnetic resonance imaging, angiography, and histological investigation were performed.

Results

One week after EMS, on histological examination of both the ICAO and control groups it was found that the transplanted temporal muscle had adhered to the arachnoid via a granulation zone, which was enriched with immune cells such as macrophages associated with the angiogenic process. Four weeks after EMS, angiography and histological examination of the ICAO group showed patent anastomoses between the external carotid artery and the cortical arteries without any detectable boundary between the temporal muscle and the cerebral cortex. In contrast, histological examination of the control group found scar tissue between the cerebral cortex and temporal muscle.

Conclusions

The initial step for formation of anastomoses resembles the process of wound healing associated with repair processes such as active proliferation of macrophages and angiogenesis within the new connective tissue. Functional revascularization requires a suitable environment (such as tissue containing vascular beds) and stimulus (such as ischemia) to induce vascular expansion.

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Takayuki Oku, Masami Fujii, Nobuhiro Tanaka, Hirochika Imoto, Joji Uchiyama, Fumiaki Oka, Ichiro Kunitsugu, Hiroshi Fujioka, Sadahiro Nomura, Koji Kajiwara, Hirosuke Fujisawa, Shoichi Kato, Takashi Saito and Michiyasu Suzuki

Object

Focal brain cooling has been recognized to have a suppressive effect on epileptiform discharges or a protective effect on brain tissue. However, the precise influence of brain cooling on normal brain function and histology has not yet been thoroughly investigated. The aim of this study was to investigate the neurophysiopathological consequences of focal cooling and to detect the threshold temperature that causes irreversible histological change and motor dysfunction.

Methods

The experiments were performed in adult male Sprague-Dawley rats (weighing 250–350 g) after induction of halothane anesthesia. A thermoelectric chip (6 × 6 × 2 mm) was used as a cooling device and was placed on the surface of the sensorimotor cortex after a 10 × 8–mm craniotomy. A thermocouple was placed between the chip and the brain surface. Focal cooling of the cortex was performed at the temperatures of 20, 15, 10, 5, 0, and −5°C for 1 hour (5 rats in each group). Thereafter, the cranial window was repaired. Motor function was evaluated using the beam-walking scale (BWS) every day for 7 days. The rats were killed 7 days after the operation for histological examination with H & E, Klüver-Barrera, glial fibrillary acidic protein, and terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate nick-end labeling stainings. The authors also euthanized some rats 24 hours after cooling and obtained brain sections by the same methods.

Results

The BWS score was decreased on the day after cooling only in the −5°C group (p < 0.05), whereas the score did not change in the other temperature groups. Histologically, the appearance of cryoinjury such as necrosis, apoptosis, loss of neurons, and marked proliferation of astrocytes at the periphery of the lesion was observed only in the −5°C group, while no apparent changes were observed in the other temperature groups.

Conclusions

The present study confirmed that the focal cooling of the cortex for 1 hour above the temperature of 0°C did not induce any irreversible histological change or motor dysfunction. These results suggest that focal brain cooling above 0°C has the potential to be a minimally invasive and valuable modality for the treatment of severe brain injury or to assist in the examination of brain function.

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Hiroyuki Hao, Koji Iihara, Hatsue Ishibashi-Ueda, Fumio Saito and Seiichi Hirota

Object

Preoperative clinical risk classification of carotid artery (CA) stenosis anticipates the outcome of CA intervention. A higher incidence of neurological morbidity was noted after CA stenting (CAS) in patients with medical risks than in those without risks. However, little is known about the correlation between clinical risks and plaque composition. The purpose of this study was to characterize the CA plaque histology in 3 groups of patients who were classified based on clinical risks for carotid endarterectomy (CEA). Furthermore, the authors examined whether the plaque with high embolic potential after CA intervention, particularly CAS, could be predicted based on clinical risks for CEA.

Methods

Patients were divided into 4 groups, according to the CEA risk classification system, and 3 groups with more than 10 cases were enrolled in this study as follows: absence of all angiographic, medical, and neurological risks (Grade I, 27 cases); presence of medical risk, but no neurological risk (Grade III, 31 cases); and presence of neurological risk (Grade IV, 17 cases). Histopathological characteristics of CA plaques, including fibrous cap thickness, plaque disruption, thrombus formation, intraplaque hemorrhage (IPH), and adipophilin expression were examined without information regarding clinical status.

Results

Plaques in patients in Grades III and IV demonstrated a thin fibrous cap and enhanced IPH, compared with those in Grade I. Plaques in patients in Grade IV showed more adipophilin-expressing macrophages in the fibrous cap than in those of the other groups.

Conclusions

Plaques in Grades III and IV patients were characterized by thin fibrous cap atheroma with IPH. Adipophilin-positive macrophage infiltration in the fibrous cap might be correlated with instability in neurological status. The plaque morphology in patients with medical and neurological risks needs to be examined carefully with the aid of imaging modalities. In plaques demonstrating a thin fibrous cap and IPH, the CAS procedure should be avoided and CEA should be performed instead.

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Koji Yoshida, Kuniaki Ogasawara, Hiroaki Saura, Hideo Saito, Masakazu Kobayashi, Kenji Yoshida, Kazunori Terasaki, Shunrou Fujiwara and Akira Ogawa

OBJECT

Cognitive function is often improved or impaired after carotid endarterectomy (CEA) for patients with cerebral hemodynamic impairment. Cerebral glucose metabolism measured using positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) correlates with cognitive function in patients with neurodegenerative diseases. The present study aimed to determine whether postoperative changes in cerebral glucose metabolism are associated with cognitive changes after CEA.

METHODS

In patients who were scheduled to undergo CEA for ipsilateral internal carotid artery (ICA) stenosis (≥ 70% narrowing), cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to acetazolamide were assessed preoperatively using brain perfusion single-photon emission computed tomography (SPECT). CBF measurement using SPECT was also performed immediately after CEA. For patients with reduced preoperative CVR to acetazolamide in the cerebral hemisphere ipsilateral to surgery, cerebral glucose metabolism was assessed using FDG-PET before surgery and 3 months after surgery and was analyzed using 3D stereotactic surface projection. Neuropsychological testing was also performed preoperatively and 3 months postoperatively.

RESULTS

Twenty-two patients with reduced preoperative CVR to acetazolamide successfully underwent FDG-PET studies and neuropsychological testing before and after CEA. Seven, 9, and 6 patients were defined as showing improved, unchanged, and impaired postoperative cognition, respectively, based on the neuropsychological assessments. The cortical area with increased postoperative glucose metabolism was greater in patients with improved postoperative cognition than in those with unchanged (p < 0.001) or impaired (p < 0.001) postoperative cognition. The cortical area with decreased postoperative glucose metabolism was greater in patients with impaired postoperative cognition than in those with improved (p < 0.001) or unchanged (p < 0.001) postoperative cognition. All 7 patients with improved cognition exhibited postoperative hemispheric increases in glucose metabolism, while 5 of the 6 patients with impaired cognition exhibited postoperative hemispheric decreases in glucose metabolism. Brain perfusion SPECT revealed that the latter 6 patients experienced postoperative cerebral hyperperfusion, and 2 of the 6 patients exhibited cerebral hyperperfusion syndrome. The cortical area with decreased postoperative glucose metabolism in these 2 patients was greater than that in other patients.

CONCLUSIONS

Postoperative changes in cerebral glucose metabolism, as measured using FDG-PET, are associated with cognitive improvement and impairment after CEA.

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Kenji Yagi, Hiroshi Nakagawa, Toshiyuki Okazaki, Shinsuke Irie, Toru Inagaki, Osamu Saito, Shinji Nagahiro and Koji Saito

OBJECTIVE

Anterior cervical discectomy and fusion (ACDF) procedures are performed to treat patients with cervical myelopathy or radiculopathy. Dysphagia is a post-ACDF complication. When it coincides with prevertebral space enlargement and inflammation, surgical site infection and pharyngoesophageal perforation must be considered. The association between dysphagia and prevertebral inflammation has not been reported. The authors investigated factors eliciting severe dysphagia and its relationship with prevertebral inflammation in patients who had undergone ACDF.

MATERIALS

The clinical data of 299 patients who underwent 307 ACDF procedures for cervical radiculopathy or myelopathy at Kushiro Kojinkai Memorial Hospital and Kushiro Neurosurgical Hospital between December 2007 and August 2014 were reviewed.

RESULTS

After 7 ACDF procedures (2.3%), 7 patients suffered severe prolonged and/or delayed dysphagia and odynophagia that prevented ingestion. In all 7 patients the prevertebral space was enlarged. In 5 (1.6%) the symptom was thought to be associated with prevertebral soft-tissue edema; in all 5 an inflammatory response, hyperthermia, and an increase in the white blood cell count and in C-reactive protein level was observed. After 2 procedures (0.7%), we noted prevertebral hematoma without an inflammatory response. None of the patients who had undergone 307 ACDF procedures manifested pharyngoesophageal perforation or surgical site infection.

CONCLUSIONS

Severe dysphagia and odynophagia are post-ACDF complications. In most instances they are attributable to prevertebral soft-tissue edema accompanied by inflammatory responses such as fever and an increase in the white blood cell count and in C-reactive protein. In other cases these anomalies are elicited by hematoma not associated with inflammation.