Biomedical subjects

Taku Sugawara

Publications and source records attributed to Taku Sugawara.

At least 19 recordsLinked to original sources

PubMed2006

Dural substitute with polyglycolic acid mesh and fibrin glue for dural repair: technical note and preliminary results.

BACKGROUND: An ideal dural substitute that enables watertight closure, has sufficient strength, and can be absorbed without remnant materials that induce inflammation, adhesion, and infection is not available. The purpose of this study was to evaluate the efficacy of a bioabsorbable polyglycolic acid (PGA) mesh and fibrin glue as a substitute for dural repair. METHODS: Altogether, 10 patients with noted dural tears during extradural spinal surgery and 20 patients who underwent durotomy for intradural spinal surgery were included in this study. In a series of 20 consecutive cases, dural closure was performed by suture and fibrin glue. In the subsequent 10 consecutive patients, dural closure was performed by suture and fibrin glue with the use of absorbable PGA mesh. The medical records and magnetic resonance imaging (MRI) of the surgical site were retrospectively reviewed to evaluate the presence of a cerebrospinal fluid (CSF) fistula or leakage after the surgery. RESULTS: A CSF fistula occurred in five patients who underwent dural repair with fibrin glue alone, and postoperative MRI showed CSF leakage in two patients with incidental dural tears after laminectomy for ossification of ligamentum flavum. No CSF fistula was present in patients who underwent dural repair using PGA mesh and fibrin glue, and no adverse effects or complications were encountered postoperatively. Follow-up MRI revealed no evidence of CSF leakage around the reconstructed dura mater. CONCLUSIONS: The use of PGA mesh and fibrin glue for the repair of dura mater is a useful method of preventing CSF leakage in spinal surgery.

Adolescent↗

PubMed2006

Overexpression of SOD1 in transgenic rats attenuates nuclear translocation of endonuclease G and apoptosis after spinal cord injury.

Spinal motor neurons are selectively vulnerable after spinal cord injury (SCI). Recent studies suggest they undergo apoptosis after caspase activation through a mitochondria-dependent apoptosis pathway, and that oxidative stress after SCI is likely to play a role. However, other signaling pathways of apoptosis that involve mitochondria have not been thoroughly studied after SCI. Apoptosis-inducing factor (AIF) and endonuclease G (EndoG) are mitochondrial apoptogenic proteins that are capable of inducing neuronal apoptosis when translocated from mitochondria to nuclei through a caspase-independent pathway. In this study, we examined translocation of these proteins and apoptotic cell death of motor neurons. The role of oxidative stress was also studied using transgenic (Tg) rats that overexpress the intrinsic antioxidant copper/zinc-superoxide dismutase (SOD1). Western blots and an activity assay demonstrated that a greater amount of SOD1 and higher activity of SOD presented in mitochondria of Tg rats compared with wild-type (Wt) rats. Immunohistochemistry and Western blots showed translocation of EndoG and AIF from mitochondria to nuclei in motor neurons 1 day after SCI in both groups of rats. However, there was significantly less translocation of EndoG in the Tg rats compared with the Wt rats. Less apoptotic cell death was detected in the Tg rats than in the Wt rats 3 days after SCI. These results suggest that translocation of EndoG and AIF from mitochondria to nuclei may initiate a caspase-independent pathway of apoptosis. An increased level of SOD1 in mitochondria conceivably reduces oxidative stress, thereby attenuating EndoG translocation, and resulting in reduction of caspase-independent apoptosis.

Animals↗

PubMed2005

Candesartan reduces superoxide production after global cerebral ischemia.

Excessive superoxide production after cerebral ischemia is known to mediate neuronal injury. Angiotensin II type 1 receptor activation results in production of superoxide, but whether angiotensin II type 1 receptor blockade prevents production of superoxide and subsequent neuronal injury after ischemia remains unclear. Normotensive rats received the angiotensin II type 1 receptor blocker, candesartan or only vehicle before induction of global cerebral ischemia. Approximately 30% of the hippocampal CA1 neurons survived in candesartan-treated animals, whereas only 2% of neurons survived in vehicle-treated animals. Superoxide production was significantly less in these vulnerable neurons in candesartan-treated animals than in vehicle-treated animals. Angiotensin II type 1 receptor may have an essential role in superoxide production and subsequent injury in vulnerable neurons after global cerebral ischemia.

Animals↗

PubMed2005

Akt/Bad signaling and motor neuron survival after spinal cord injury.

The serine-threonine kinase Akt is a cell survival signaling pathway that inactivates the proapoptotic BCL-2 family protein Bad and promotes cell survival in cerebral ischemia. Involvement of the Akt/Bad signaling pathway after spinal cord injury (SCI) is, however, uncertain. Our results showed that phospho-Akt (serine-473) and phospho-Bad (serine-136) were significantly upregulated at 1 day after SCI. In addition, phospho-Akt and phospho-Bad were colocalized in motor neurons that survived SCI and inhibition of PI3-K reduced expression of phospho-Akt and phospho-Bad. Dimerization of Bad with 14-3-3 in the cytosol was increased whereas Bad/Bcl-XL binding in the mitochondria was decreased after SCI. We further found that reduced oxidative stress by SOD1 overexpression in rats enhanced the expression of phospho-Akt, phospho-Bad, Bad/14-3-3 binding and reduced Bad/Bcl-XL binding after SCI, as compared to wild-type rats. We conclude that oxidative stress may play a role in modulating Akt/Bad signaling and subsequent motor neuron survival after SCI.

14-3-3 Proteins↗

PubMed2005

Overexpression of human copper/zinc-superoxide dismutase in transgenic animals attenuates the reduction of apurinic/apyrimidinic endonuclease expression in neurons after in vitro ischemia and after transient global cerebral ischemia.

Oxidative stress after ischemia/reperfusion has been shown to induce DNA damage and subsequent DNA repair activity. Apurinic/apyrimidinic endonuclease (APE) is a multifunctional protein in the DNA base excision repair pathway which repairs apurinic/apyrimidinic sites in DNA. We investigated the involvement of oxidative stress and expression of APE in neurons after oxygen-glucose deprivation and after global cerebral ischemia. Our results suggest that overexpression of human copper/zinc-superoxide dismutase reduced oxidative stress with a subsequent decrease in APE expression. Production of oxygen free radicals and inhibition of the base excision repair pathway may play pivotal roles in the cell death pathway after ischemia.

Animals↗

PubMed2005

Novel dural closure technique using polyglactin acid sheet prevents cerebrospinal fluid leakage after spinal surgery.

OBJECTIVE: Extradural or subcutaneous cerebrospinal fluid (CSF) leakage is a common complication after spinal surgery and is associated with the risks of poor wound healing, meningitis, and pseudomeningocele. Numerous methods to prevent postoperative CSF leakage are available, but pressure-tight dural closure remains difficult, especially with synthetic surgical membranes. The efficacy of a novel dural closure technique was assessed by detecting extradural or subcutaneous CSF leakage on magnetic resonance imaging. METHODS: The novel dural closure technique using absorbable polyglactin acid sheet and fibrin glue and the conventional procedure using only fibrin glue were evaluated retrospectively by identifying extradural or subcutaneous CSF leakage on magnetic resonance imaging scans in the acute (2-7 d) and chronic (3-6 mo) postoperative stages after spinal intradural surgery in 53 patients. RESULTS: The incidence of extradural and subcutaneous CSF leakage was significantly lower (P < 0.05) in the acute (20%) and chronic (0%) stages using polyglactin acid sheet and fibrin glue in 15 patients compared with that in the acute (81%) and chronic (24%) stages using only fibrin glue in 38 patients. One patient in the fibrin glue-only group required repair surgery for cutaneous CSF leakage. CONCLUSION: The combination of polyglactin acid sheet and fibrin glue can achieve water-tight closure after spinal intradural surgery and can minimize the risk of intractable postoperative CSF leakage. This simple, economical technique is recommended for dural closure after spinal intradural surgery.

Adolescent↗

PubMed2005

[Four cases of spontaneous spinal epidural hematoma].

Spontaneous spinal epidural hematoma (SSEH) is a rare clinical entity. Although approximately 500 cases have been reported, controversy exists concerning timing of the treatment and the validity of decompression surgery. We recently encountered four cases of SSEH. Evacuation of the hematoma was carried out in two patients with severe or persistent neurological deficits. Other two patients were treated conservatively because of the rapid resolution of the symptoms. All four patients improved after the treatment; three patients fully recovered and one patient required rehabilitation for moderate quadriparesis. Many previous reports recommended decompression surgery within 48 hours after the onset, however, one patient in our series fully recovered after surgery 4 days after the onset. We reviewed 183 operative cases of SSEH with incomplete neurological deficits in the literature and found that 93% of the patients who underwent surgery more than 48 hours after symptom onset showed good neurological recovery. Conservative treatment should be undertaken for rapidly improving patients, but surgical intervention should be considered in symptomatic patients regardless of the time from the onset.

Adolescent↗

PubMed2004

Neuronal death/survival signaling pathways in cerebral ischemia.

Cumulative evidence suggests that apoptosis plays a pivotal role in cell death in vitro after hypoxia. Apoptotic cell death pathways have also been implicated in ischemic cerebral injury in in vivo ischemia models. Experimental ischemia and reperfusion models, such as transient focal/global ischemia in rodents, have been thoroughly studied and the numerous reports suggest the involvement of cell survival/death signaling pathways in the pathogenesis of apoptotic cell death in ischemic lesions. In these models, reoxygenation during reperfusion provides a substrate for numerous enzymatic oxidation reactions. Oxygen radicals damage cellular lipids, proteins and nucleic acids, and initiate cell signaling pathways after cerebral ischemia. Genetic manipulation of intrinsic antioxidants and factors in the signaling pathways has provided substantial understanding of the mechanisms involved in cell death/survival signaling pathways and the role of oxygen radicals in ischemic cerebral injury. Future studies of these pathways may provide novel therapeutic strategies in clinical stroke.

Animals↗

PubMed2004

Direct repair of a blisterlike aneurysm on the internal carotid artery with vascular closure staple clips. Technical note.

Vascular closure staple clips made of titanium were originally developed for microvascular anastomosis. Clinical applications for these clips include arteriotomy closure for carotid endarterectomy, extracranial-intracranial bypass, and dural closure. This is the first report in which vascular closure staple clips have been used successfully for direct repair of a tear on the internal carotid artery (ICA). This report involves a 65-year-old man who presented with sudden onset of headache. Admission computerized tomography scans demonstrated a diffuse and thick subarachnoid hemorrhage in the basal cisterns. Cerebral angiograms demonstrated a broad-based, small bulge on the superomedial wall of the left ICA. Intraoperatively, an extremely thin-walled aneurysm was seen on the segment of the ICA at the C-2 vertebral level. The aneurysm ruptured abruptly, although no surgical manipulation was being performed on the aneurysm itself. After temporary clips were applied on the vessel, a large tear of the ICA was repaired with vascular closure staple clips. Reconstruction with the vascular closure staple clips required only a short period of temporary occlusion of the ICA. Postoperative angiograms revealed reduction of the aneurysm bulge and good patency of the ICA. The postoperative course was uneventful, and the patient has been free of symptoms. The vascular closure staple clipping procedure is useful for urgent repair of an aneurysm tear. This method is a new treatment option for these fragile aneurysms in cases in which other options, such as encircling clips or bypass procedures, may have drawbacks or be impossible.

Aged↗

PubMed2004

Simultaneous microscopic and endoscopic monitoring during surgery for internal carotid artery aneurysms.

OBJECT: The authors of this study evaluated the efficacy of simultaneous microscopic and endoscopic monitoring during surgery for internal carotid artery (ICA) aneurysms. METHODS: The endoscopic technique was applied during microsurgery in 11 patients with 13 aneurysms. Nine of these lesions were located on the posterior communicating artery (PCoA), three in the paraclinoid region, and one on the anterior choroidal artery (AChA). Eight patients had unruptured aneurysms and three had ruptured aneurysms. The endoscope was introduced after first exposing the aneurysm through the microscope and was gripped firmly by an airlocked holding arm fitted with a steering system throughout the entire surgery, including dissection of the perforating arteries and application of the aneurysm clips. Regarding paraclinoid aneurysms, clips were applied through direct visualization of the ophthalmic artery and the proximal neck. In a case involving a superior hypophyseal artery aneurysm in the paraclinoid segment, a ring clip was applied without removing the bone structure around the optic canal. In all aneurysms of the PCoA and the AChA, perforating arteries behind the lesion were identified and dissected using endoscopic control. The aneurysm clip was applied in the best position in a single attempt in 10 of 11 patients. There was no surgical complication related to the endoscopic procedures. CONCLUSIONS: Simultaneous monitoring with the microscope and endoscope is extremely useful in applying clips to ICA aneurysms. This combined method allows for direct dissection of the aneurysm, perforating vessels, and the main trunk in an area not visible through the microscope's eyepiece and promises better surgical results.

Adult↗

PubMed2004

[Supratentorial primitive neuroectodermal tumor: report of a surgical case].

We reported a rare case of supratentorial primitive neuroectodermal tumors (sPNET) and reviewed the literature. A 15-year-old girl presented with a one-month history of headache and vomiting. CT scans showed a huge, solid and cystic tumor with calcification, occupying the left anterior cranial fossa. The solid portion of the tumor was hypointense on T1-weighted images, slightly hyperintense on T2-weighted images, hyperintense on diffusion- weighted images, isointense on fluid-attenuated inversion recovery (FLAIR) images, and strongly enhanced after administration of contrast medium. The expansile tumor had a broad attachment to the dura matter of the anterior cranial fossa. The patient underwent an uneventful extirpation of the tumor. Microscopically, the solid tumor contained small, round poorly-differentiated cells with pleomorphic nuclei and brisk mitotic activity. The tumor cells were immunoreactive for synaptophysin and GFAP, whereas lack of MIC2 gene product expression was confirmed using the monoclonal antibody 12E7. The MIB-1-positive rate was 43%. The histological diagnosis was sPNET. Postoperatively, a dose of 30.6Gy was administrated to the whole brain and a boost of 19.6Gy to the T2-hyperintensity lesion. The patient successively received a dose of 30.4Gy to the whole spine and Linac stereotactic radiotherapy with a marginal dose of 16.8Gy at the tumor bed. Three months after radiotherapy the patient received chemotherapy using carboplatin and etoposide. Follow-up MR images showed no evidence of recurrent tumor 5 months after the radiochemotherapy. On the basis of MR findings on both diffusion-weighted and FLAIR images, preoperative diagnosis of sPNET may be important for choosing appropriate therapeutic strategies for this tumor.

Adolescent↗

PubMed2004

[Unusual MR appearance of intracranial dissemination from cervical glioblastoma].

We reported a rare case of cervical glioblastoma with intracranial dissemination at an early stage of clinical course and reviewed the literature. An 8-year-old girl presented with failure of vision 3 months prior to admission to our hospital. Neurological examination on admission disclosed no definitive abnormalities except for bilateral visual disturbance and optic atrophy. Cranial MR images revealed a homogeneously enhancing tumor in the left sylvian fissure. Multiple spotty T2-hyperintensity lesions without contrast enhancement were also disclosed in bilateral cerebellum. Spinal MR images showed an enhancing tumor at C7 and tiny enhancing lesions on the surface of T11. The patient underwent an uneventful excision of the exophytic tumor at C7. The histological diagnosis was glioblastoma. The enhancing tumor in the left sylvian fissure treated by Linac stereotactic radiotherapy with a marginal dose of 38.4Gy in 12 fractions has diminished, whereas the residual tumor at C7 remained unchanged after radiation of 44Gy. In contrast, the multiple spotty lesions without contrast enhancement dispersedly spread in the cerebellum and infiltrated into brain stem despite 4 courses of chemotherapy using ifosfamide, cisplatin, and etoposide. Stereotactic biopsy of the multiple spotty lesions in the cerebellum was performed. Histological examination revealed anaplastic astrocytoma. The patient died 2 weeks after the biopsy despite additional chemotherapy and focal irradiation to the cerebellum. Early detection and selection of optimal therapeutic strategies are important in management of spinal glioblastoma with subarachnoid dissemination, since neuroradiological findings and therapeutic sensitivity are varied according to differentiation of disseminated tumors.

Brain Neoplasms↗

PubMed2003

The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebral ischemia.

The serine proteases tissue plasminogen activator, plasmin, and thrombin and their receptors have previously been suggested to contribute to neuronal damage in certain pathological situations. Here we demonstrate that mice lacking protease-activated receptor 1 (PAR1) have a 3.1-fold reduction in infarct volume after transient focal cerebral ischemia. Intracerebroventricular injection of PAR1 antagonist BMS-200261 reduced infarct volume 2.7-fold. There are no detectable differences between PAR1-/- and WT mice in cerebrovascular anatomy, capillary density, or capillary diameter, demonstrating that the neuroprotective phenotype is not likely related to congenital abnormalities in vascular development. We also show that the exogenously applied serine proteases thrombin, plasmin, and tissue plasminogen activator can activate PAR1 signaling in brain tissue. These data together suggest that if blood-derived serine proteases that enter brain tissue in ischemic situations can activate PAR1, this sequence of events may contribute to the harmful effects observed. Furthermore, PAR1 immunoreactivity is present in human brain, suggesting that inhibition of PAR1 may provide a novel potential therapeutic strategy for decreasing neuronal damage associated with ischemia and blood-brain barrier breakdown.

Animals↗

PubMed2003

Treatment with dihydroethidium reduces infarct size after transient focal cerebral ischemia in mice.

A transient focal ischemia model with C57Bl/6 mice was used to investigate whether dihydroethidium is neuroprotective. Different doses (25, 50, 100 mg/kg body weight) were used for pretreatment and the lowest effective dose was used for delayed treatment 1 and 2 h after reperfusion. Our results demonstrate that all the doses used for treatment reduced infarct volume. We conclude that dihydroethidium is neuroprotective by reducing superoxide in mice after stroke.

Animals↗

PubMed2003

Copper-zinc superoxide dismutase affects Akt activation after transient focal cerebral ischemia in mice.

BACKGROUND AND PURPOSE: The serine-threonine kinase Akt is activated by phosphorylation at serine-473. After phosphorylation, activated Akt inactivates BAD or caspase-9 or other apoptogenic components, thereby inhibiting cell death. In this study we examined the relationship between Akt phosphorylation and oxidative stress after transient focal cerebral ischemia (FCI) using copper-zinc superoxide dismutase (SOD1) transgenic (Tg) mice. METHODS: The mice were subjected to 60 minutes of middle cerebral artery occlusion by intraluminal suture blockade followed by 1, 4, and 24 hours of reperfusion. Phospho-Akt expression was examined by immunohistochemistry and Western blot analysis. Production of superoxide anion was assessed by the hydroethidine method in both wild-type mice and SOD1 Tg mice. DNA fragmentation was evaluated by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL). RESULTS: Immunohistochemistry demonstrated that phospho-Akt was constitutively expressed and was decreased in the ischemic core as early as 1 hour after reperfusion, whereas it was temporally increased in the cortex at 4 hours. Phospho-Akt expression was enhanced in the SOD1 Tg mice. Western blot analysis showed that phospho-Akt was maximized 4 hours after reperfusion in the wild-type mice, whereas phospho-Akt was increased as early as 1 hour after ischemia in the SOD1 Tg mice. There was a significant decrease in TUNEL-positive cells in the SOD1 Tg mice compared with the wild-type mice. CONCLUSIONS: The present study suggests that SOD1 may contribute to the early activation of the Akt cell survival signaling pathway and may attenuate subsequent DNA damage after transient FCI.

Animals↗

PubMed2003

Induction of heat shock protein 40 and GrpE mRNAs following transient focal cerebral ischemia in the rat.

Cerebral ischemia is associated with the induction of several heat shock proteins (HSPs), but the effects on HSP40 and GrpE are less clear. The present study investigated the induction of Hsp40 and GrpE mRNAs following 30 min of middle cerebral artery occlusion in the rat model. Reverse transcription-polymerase chain reaction (PCR) and in situ hybridization analyses showed significant induction of both mRNAs in the ischemic cortex. These results demonstrate the synergic induction of HSP70 molecular chaperone machinery in cerebral ischemia.

Animals↗

PubMed2003

Reactive oxygen radicals and pathogenesis of neuronal death after cerebral ischemia.

Reactive oxygen species have been implicated in brain injury after cerebral ischemia. These oxidants can damage proteins, lipids, and DNA, and lead to cell injury and necrosis. Oxidants are also initiators in intracellular cell death signaling pathways that may lead to apoptosis. The possible targets of this redox signaling include mitochondria, death membrane receptors, and DNA repair enzymes. Genetic manipulation of intrinsic antioxidants and the factors in the signaling pathways has provided substantial progress in understanding the mechanisms in cell death signaling pathways and involvement of oxygen radicals in ischemic brain injury. Future studies of these pathways may provide novel therapeutic strategies in clinical stroke.

Animals↗

PubMed2003

Temporal profile of angiogenesis and expression of related genes in the brain after ischemia.

Angiogenesis is an intricately regulated phenomenon. Its mechanisms in the ischemic brain have not been clearly elucidated. The authors investigated expression of angiogenesis-related genes using a complementary DNA (cDNA) array method as well as Western blotting and immunohistochemistry, and compared these studies with a temporal profile of angiogenesis in mouse brains after ischemia. The number of vessels significantly increased 3 days after injury, and proliferating endothelial cells increased as early as 1 day. This means that angiogenesis occurs immediately after the injury. Ninety-six genes implicated in angiogenesis were investigated with a cDNA array study. It was found that 42, 29, and 13 genes were increased at 1 hour, 1 day, and 21 days, respectively. Most of the well-known angiogenic factors increased as early as 1 hour. Vessel-stabilizing factors such as thrombospondins also increased. At 1 day, however, thrombospondins decreased to lower levels than in the control, indicating a shift from vascular protection to angiogenesis. At 21 days, many genes were decreased, but some involved in tissue repair were newly increased. Western blotting and immunohistochemistry showed findings compatible with the cDNA array study. Many molecules act in an orchestrated fashion in the brain after ischemia and should be taken into account for therapeutic angiogenesis for stroke.

Angiogenesis Inducing Agents↗