Muneyoshi Yasuda

Activation of PI3 Kinase/Akt Signaling in Chronic Subdural Hematoma Outer Membranes

Chronic subdural hematoma (CSDH) is an angiogenic disease that is recognized as a cause of treatable dementia with unknown pathogenesis. Vascular endothelial growth factor (VEGF), a potent growth factor regulating angiogenesis through the phosphatidylinositol 3-kinase (PI3-kinase)/Akt pathway, has been implicated in its etiology. The status of this signaling pathway in CSDH outer membranes was examined in the present study, using outer membranes obtained during trepanation surgery. Expressions of PI3-kinase, PKB-kinase, Akt, phosphorylated Akt at Ser(473) (p-Akt), endothelial nitric oxide synthase (eNOS), vascular endothelial-cadherin (VE-cadherin), and actin were examined by Western blot analysis, together with their immunohistochemistry. PI3-kinase, Akt, eNOS, and VE-cadherin were detected in all cases. The magnitude of the expression of p-Akt varied among cases; however, the localization was revealed to be present in endothelial cells of vessels in CSDH outer membranes, together with VEGF and VE-cadherin detected in endothelial cells of vessels. These findings suggest that the PI3-kinase/Akt signaling is activated in CSDH outer membranes, and indicate the possibility that the PI3 kinase/Akt pathway might be activated by VEGF and play a critical role in the angiogenesis of CSDH.

Adiponectin activates endothelial nitric oxide synthase through AMPK signaling after subarachnoid hemorrhage

Adiponectin is produced from fatty tissue and has been reported to be involved with metabolic syndrome. Recently, adiponectin has been demonstrated to play a neuroprotective role against cerebral ischemia. In this study, we explored the time-course serial expression changes of adiponectin in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH) and the effects of adiponectin on cerebral arteries. The concentrations of adiponectin were measured serially until day 14 in CSF of 8 patients with SAH. The CSF samples obtained from 6 patients suffering from an unruptured aneurysm were used as controls. Serum samples were collected from 6 healthy adult volunteers. Rat cerebral arteries were incubated with adiponectin (2μg/ml). Western blot analysis using AMP-activated protein kinase α (AMPKα), phosphorylated (p)-AMPKα at Thr(172), endothelial nitric oxide synthase (eNOS), p-eNOS at Ser(1177) and actin antibodies was then performed. The adiponectin concentrations in serum and control CSF were 17,670±3748ng/ml and 9.2±3.0ng/ml, respectively. After SAH, the concentration of adiponectin in the CSF significantly increased on the first post-SAH day and gradually decreased thereafter. Adiponectin significantly phosphorylated both the AMPKα and eNOS of the cerebral arteries. Our findings suggest that adiponectin is significantly increased in the CSF after SAH, resulting in the activation of AMPKα and eNOS. Adiponectin plays an important role against cerebral vasospasm via the AMPK/eNOS signaling pathway.

Anterolateral approach without fixation for resection of an intradural schwannoma of the cervical spinal canal: technical note.

OBJECTIVE Although an anterolateral approach is an ideal approach to the anterior part of the cervical spinal canal, it is not often used because of various technical difficulties. This article presents the case of a patient with an intradural schwannoma ventrolateral to the spinal cord and describes the technique, anterolateral surgery without fixation, that was used to remove it. CASE PRESENTATION A 71-year-old man presented with neck pain and easy fatigability of the legs. Magnetic resonance imaging showed an intradural tumor ventrolateral to the spinal cord at the C3 level. The diagnosis was a schwannoma. TECHNIQUE A right anterolateral approach was selected for the resection. In the dissection between the sternocleidomastoid muscle and the internal jugular vein, the accessory nerve was retracted with the fat tissue. At C3, the prevertebral aponeurosis was laterally retracted to protect the sympathetic chain. The C3 transverse process was rongeured, and the vertebral artery was shifted laterally with the venous plexus. The C2-C3 uncovertebral joint and the right third of the C3 body were removed (partial corpectomy). The tumor was easily found in the dural sac and was totally removed. The surgical wound was closed in a watertight fashion. No fixation was necessary. The symptoms improved after the operation. DISCUSSION The anterolateral approach is one of the best approaches for resecting ventrally located intradural lesions because it allows minimally invasive surgery. Control and protection of the accessory nerve, sympathetic chain, and vertebral artery are the keys to success.

Activation of JAK-STAT3 signaling pathway in chronic subdural hematoma outer membranes

Chronic subdural hematoma (CSDH) is an inflammatory disease, the mechanism of which still remains to be elucidated. Interleukin-6 (IL-6), one of the inflammatory cytokines regulating janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, is expressed in human CSDH fluid. The status of this signaling pathway in human CSDH outer membranes was examined in the present study using outer membranes obtained during trepanation surgery. Concentrations of IL-6 in human CSDH fluids were measured using an enzyme immuno-assay kit. Expression patterns of JAK1, STAT1, phosphorylated (p)-STAT1 at Tyr(701) and at Ser(727), STAT3, p-STAT3 at Tyr(705) and at Ser(727) and actin in outer membranes were examined by Western blot analysis and immunohistochemistry. IL-6 is significantly expressed in human CSDH fluids compared with control cerebrospinal fluid. JAK1, STAT1 and STAT3 were detected in all cases. The expression of p-STAT3 at Tyr(705) is more significant compared with that of p-STAT1 at Tyr(701). In some cases, p-STAT3 at Ser(727) could also be detected, while p-STAT1 at Ser(727) could not. The localizations of STAT1 and STAT3 were revealed to be present in fibroblasts in human CSDH outer membranes, especially when p-STAT3 at Tyr(705) was in the nuclei of fibroblasts. These findings suggest that JAK1-STAT3 signaling is dominantly activated in fibroblasts of human CSDH outer membranes compared with STAT1 and indicate the possibility that this JAK1-STAT3 pathway might be activated by IL-6 and play a critical role in progression of human CSDH.

Vertebral Artery Loop—A Cause of Cervical Radiculopathy

OBJECTIVE To report a case of cervical radiculopathy caused by an anomalous vertebral artery (VA) and illustrate the efficacy of microvascular decompression by the anterolateral approach. METHODS A 50-year-old woman was referred because of an 8-year history of progressive left C6 radiculopathy refractory to other forms of treatment, including C5-6 anterior cervical discectomy. Clinical and radiologic evaluation showed an abnormally tortuous loop of V2 causing direct neurovascular compression. RESULTS A left cervical anterolateral approach was used to expose the anomalous loop. After a generous bony decompression, the loop was identified, and the artery was mobilized and ultimately separated from the C6 nerve root removing the direct pulsatile compression. CONCLUSIONS Cervical root compression by an aberrant or anomalous extracranial VA is a rare cause of radiculopathy. The best management of such lesions is the anterolateral approach with bony and direct microvascular decompression.

Expression of the JAK/STAT3/SOCS3 signaling pathway in herniated lumbar discs

The inflammatory cytokine interleukin-6 (IL-6) plays an important role in causing symptoms of lumbar disk herniation. The present study clarifies the expression of the signaling pathway of IL-6 in herniated discs. Homogenates prepared from lumbar herniated discs from 10 patients were assessed. The expression of janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), phosphorylated (p)-STAT3 at Tyr(705), suppressor of cytokine signaling 3 (SOCS3) and actin was examined by Western blot analysis. The expression of JAK1, STAT3, and p-STAT3 at Tyr(705) was also examined by immunostaining. JAK1, STAT3, p-STAT3 at Tyr(705) and SOCS3 were detected in almost all cases. Immunoreactivity against JAK1 and STAT3 was observed mainly in chondrocytes, whereas immunoreactivity against p-STAT3 at Tyr(705) was observed in the nuclei of chondrocytes. The JAK/STAT signaling pathway might be activated by IL-6 and transmit messages from the cell surface to the nucleus, and the pathway is negatively regulated by SOCS3. These JAK1, STAT3 and SOCS3 molecules might tightly regulate and play a role in the degeneration of chondrocytes within herniated discs.

Activation of STAT1 in neurons following spinal cord injury in mice.

The signal transducer and activator of transcription 1 (STAT1) has been reported to be associated with neuronal cell death after cerebral ischemia. On the contrary, STAT3 has been revealed to regulate cell survival. We examined the chronological alteration and cellular localization of phosphorylated (p)-JAK1, p-STAT1 and p-STAT3 following mild spinal cord injury (SCI) in mice. Western blot analysis indicated that JAK1 is significantly phosphorylated, accompanied by the phosphorylation of STAT1 at Tyr701 within a similar timeframe. Immunofluorescence staining indicated that signal transduction of STAT3 is introduced into the nucleus of the neurons within the anterior horns; however, in mirror sections, that of STAT1 is limited to the cytoplasm. These findings suggest that STAT3 signal is predominantly transduced into the nucleus and plays a stronger role in neuronal survival than STAT1. Modulation of the functional balance between STAT1 and STAT3 might determine the survival or death of neurons after SCI.

A Simple, 10-minute Procedure for Transforaminal Injection under Ultrasonic Guidance to Effect Cervical Selective Nerve Root Block

The aim is to provide a detailed procedure of a simple and 10-minute cervical nerve root block (CNRB) under ultrasonic guidance, and to report the clinical outcomes, disorders, and complications. Records of patients who had undergone CNRB, were reviewed under ultrasonic guidance at the hospital from 2010 through 2012. The procedure is described in detail. Arm and shoulder pain was evaluated by use of the visual analogue scale (VAS). Forty-three patients agreed to undergo CNRB under ultrasonic guidance. Nerve roots from C5 to C8 were affected in 41, and these nerve roots were readily distinguished. Two of the 43 participants did not receive injections because impediments in visualizing the affected nerve root. Of the 41 who received injections, radicular pain immediately disappeared in 39, who continued to feel pain relief 1 month later. However, pain recurred in 15 patients (38%), of whom 11 underwent cervical spine surgery. The rest of 24 patients felt sustained pain relief longer than 3 months after the injection, significantly. Although one patient had recurrent radicular pain 10 months later, the pain could be controlled by medication. At the final follow-up periods, 17.2 (10–24 months), the median VAS score of the patients, 23 (0 to 71 mm), was significantly improvement (P = 0.001) in comparison to before injection 88 (range; 56–100). No complications occurred. The cervical nerve root block under ultrasonic guidance simply, safely, and efficaciously decreased radicular pain for 17.2 months in 62% patients with intolerable radicular pain.

A large retro-odontoid cystic mass caused by transverse ligament degeneration with atlantoaxial subluxation leading to granuloma formation and chronic recurrent microbleeding case report

BACKGROUND CONTEXT Noninfectious nontumorous retro-odontoid masses are rare, and masses have not been reported to extensively compress the spinal cord. We encountered a case of a large retro-odontoid lesion that extensively compressed the spinal cord. CASE REPORT A 76-year-old-man reported experiencing a sudden onset of neck pain, hand and foot paresthesia, dysarthria, and dysphagia. When symptoms had not eased by 10 days of treatment with external stabilization and bed rest, he was referred to our hospital. Dynamic radiographs of the cervical spine showed that the atlantodental interval widened from 2 mm on extension to 7 mm on flexion. Computed tomography did not reveal abnormality of the odontoid process or the presence of a high-density area that could suggest calcification in or near the cystic mass. Fluid-attenuated inversion recovery axial magnetic resonance image showed a mass that was 3.0-cm wide, 2.7-cm high, and 2.5-cm thick that severely compressed the lower brain stem. T2-weighted magnetic resonance imaging showed that the mass contained a solid part posterior to the C2 dense area, extending rostrally, compatible with the presence of degenerated and hypertrophic ligaments. We performed surgical decompression of the lesion combined with atlantoaxial fixation. The partly cystic mass, which was located extradurally, had xanthochromic content, indicating microbleeding. Dysarthria and dysphagia immediately disappeared, and neurologic symptoms disappeared by 1 month. At 1-year follow-up, the patient remained symptom free, and computed tomography scans did not show recurrence of the mass. The pathologic diagnosis of degenerative ligament tissue with chronic recurrent microbleeding and associated granulation was made. DISCUSSION A possible explanation why the cyst grew to an exceptionally large size is that the transverse ligament of axis became degenerated and hypertrophic because of chronic mechanical stress by atlantoaxial subluxation. Then, a part of the ligament developed reactive granulation with small vessel formation. Finally, rupture of these small vessels caused repeated episodes of microbleeding, resulting in formation of a large cyst. The observation of degenerative ligament tissue, granulation formation, and microbleeding differentiated it from a synovial cyst or a ganglion cyst. The presence of hemosiderin deposits suggested chronic recurrent microbleeding. Taking all our findings together, we believe that our case of retro-odontoid cystic mass is different from the others that have been reported. Atlantoaxial instability may cause a large mass, such as we described here, so that careful observation is important.

Exploitation of Simple Classification and Space Created by the Tumor for the Treatment of Foramen Magnum Meningiomas.

OBJECTIVE The resection of foramen magnum meningiomas (FMMs) presents neurosurgical challenges. We propose a simple classification of the tumor location and the operating space created by the tumor to help treatment planning. METHODS We retrospectively analyzed 16 FMMs and divided them into 3 groups based on the tumor location--clival, foraminal, and atlantal tumors. The distance between the condyle and the neuraxis at the level of the foramen magnum was measured and defined as the available operative space (AOS). We also reviewed intraoperative video recordings to assess the surgical exposure of the tumor by the space created by the FMM and compared it with the AOS. RESULTS There were 4 clival, 8 foraminal, and 4 atlantal tumors. The AOS of the clival tumors was 10 mm ± 1.7, the AOS of the foraminal tumors was 18 mm ± 3.7, and the AOS of the atlantal tumors was 12 mm ± 2.1. All foraminal and atlantal tumors could be detached without a brain retractor. Because a major portion of the clival tumors was covered by the spinomedullary junction, a brain spatula was needed to obtain the required surgical space. The difference in AOS between clival and foraminal/atlantal tumors was statistically significant (P = 0.044). Although 4 patients experienced postoperative complications, the average postoperative Karnofsky performance scale score improved. The surgical complication rate was significantly lower in foraminal and atlantal FMMs than in clival FMMs (P = 0.027). CONCLUSIONS The simple classification of the tumor location helped to assess surgical difficulties. Knowledge of the space created by the FMMs between the condyle and the neuraxis is useful for planning the approach strategy, especially for estimating the available working space without resection of the occipital condyle.