Chun Kun Park

Analysis of anatomical variations of bone and vascular structures around the posterior atlantal arch using three- dimensional computed tomography angiography

OBJECTnThe current study evaluates the incidence of anatomical variations of the V(3) segment of the vertebral artery (VA) and the posterior arch of the atlas (C-1). Failure to appreciate these types of anatomical variations can cause catastrophic injury to the VA during posterior approaches to the upper cervical spine.nnnMETHODSnIn the present study, the authors analyzed the records of 1013 Korean patients who underwent computed tomography (CT) angiography to evaluate the incidence of anomalous variations in the third segment of the VA and to determine the incidence and morphometric characteristics of any detected posterior ponticuli. The authors also hoped to determine any specific imaging features that might indicate a VA anomaly around the craniovertebral junction.nnnRESULTSnThe mean age of the patients was approximately 55.7 years and the prevalence of a posterior ponticulus was 15.6%. The incidence rate of a posterior ponticulus in the male population was 19.3%, whereas in the female population it was 12.8%. The incomplete type of posterior ponticulus was more common than the complete type. The mean age of the patients with an incomplete posterior ponticulus (55.7 years) was significantly younger (p = 0.018) than the mean age of patients with a complete posterior ponticulus (57.6 years). The incidence rate of a persistent first inter-segmental artery was 4.7% and the incidence rate of a fenestrated VA was 0.6%. The area of the C-1 transverse foramen on the abnormal side was significantly smaller than that of the contralateral normal side.nnnCONCLUSIONSnThe shape of the C-1 posterior arch and the third segment of the VA are heterogeneous. Therefore, preoperative radiological studies should be performed to identify any anatomical variations. Using preoperative 3D CT angiography, we can precisely identify an anomalous VA and significantly reduce the risk of VA injury.

Expression of vascular endothelial growth factor mRNA following transient forebrain ischemia in rats

Using a reproducible two-vessel occlusion model for forebrain ischemia in rats, we investigated the temporal and spatial changes of vascular endothelial growth factor (VEGF) expression after transient forebrain ischemia with Northern blot analysis and in situ hybridization. Northern blot analysis revealed that VEGF mRNA of the hippocampus was increased from 12 h after reperfusion, with a peak at 1 day. In situ hybridization and double labeling for VEGF mRNA and glial fibrillary acidic protein showed a transient induction of VEGF mRNA in the neurons of the hippocampus from 12 h of reperfusion with a peak at 1 day, and in the astrocytes of the hippocampus, caudoputamen, thalamus and cortical regions at 1 day. After 3 days, no more VEGF signal was detected. Our results demonstrate that astrocytes and neurons each upregulate VEGF mRNA in different temporal and spatial patterns after transient forebrain ischemia in the rat, and these patterns appear to be different from those in transient focal cerebral ischemia.

Significance of laminar screw fixation in the subaxial cervical spine.

Study Design. We retrospectively reviewed 11 patients who underwent laminar screw fixation in the subaxial cervical spine. In 4 patients, laminar screws were inserted for posterior cervical arthrodesis, and in 7 patients it was used for fixation of the open laminae during laminoplasty. Objective. In this study, the author describes the technique and surgical results of translaminar screw placement in the subaxial cervical spine. Summary of Background Data. The use of laminar screws for fixation of the second cervical vertebra and upper thoracic vertebrae has been introduced as an important technique in spinal surgery because they can avoid injury to adjacent neurovascular structures. However, there have been no reports of translaminar screw use in the subaxial spine including C7. In this study, we describe the use of translaminar screws for fixation of the subaxial cervical spine in cases of degenerative or traumatic spine disease. Methods. Between June 2006 and March 2007, 34 translaminar screws were placed in 11 patients to treat trauma or degenerative disease: 6 at C7, 6 at C6, 7 at C5, 7 at C4, 7 at C3, and 1 at T1. There were 6 women and 5 men. The ages ranged from 23 to 87 years with a mean age of 61.3 years. All patients were evaluated at 6 weeks, as well as at 3 and 6 months using flexion and extension lateral radiographs. Patients requiring fusion were also evaluated with computed tomography at 3 and 6 months to verify arthrodesis. Results. The mean follow-up period was 5.7 months, at which time there was no significant complications from laminar screw placement, except for 2 asymptomatic breaches of the dorsal lamina cortex. Sound bone fusion was identified in cases where arthrodesis was the goal. No screw pullout or avulsion was identified in the laminoplasty cases. Conclusion. The translaminar screw method avoided damaging vascular structures, especially when the vertebral artery courses in the C7 transverse foramen, and it maintains solid stabilization of the subaxial cervical spine. This technique has 2 important advantages to currently used techniques: it is simpler and is not limited by the position of vascular structures. Therefore, it may be applicable to a wider number of patients, especially as it may be used in the subaxial cervical spine.

Cytotoxicity of human umbilical cord blood-derived mesenchymal stem cells against human malignant glioma cells

BackgroundMesenchymal stem cells (MSCs) represent a potential useful source for cell-based glioma therapies because these cells evidence both orthodox and unorthodox plasticity and also show tropism for cancer. In this study, the authors attempted to access the cytotoxicity of human umbilical cord blood (hUCB)-derived MSCs, with or without cytokine activations against malignant glioma cells.Materials and methodshUCB-derived MSCs were activated by interleukin-2, interleukin-15, granulocyte macrophage colony-stimulating factor, and combinations. The hUCB-derived MSCs and activated hUCB-derived MSCs were effector cells. The cytotoxicity of the unactivated hUCB-derived MSCs and activated hUCB-derived MSCs against the target cells (human malignant glioma cells) was estimated via visual survival cell assays and transwell inserts. Phenotypic changes occurring in these hUCB-derived MSCs before and after cytokine activation were determined via flow cytometry. The secreted proteins from these effector cells were estimated via enzyme-linked immunosorbent assays.ResultsWe noted a significant cytotoxicity of hUCB-derived MSCs against malignant glioma cells. In addition, the hUCB-derived MSCs activated with cytokines evidenced significantly higher cytotoxicity than that observed with unactivated hUCB-derived MSCs. Differentiated immune effectors cells from the hUCB-derived MSCs after cytokine activation were not shown to have increased in number. However, the activated hUCB-derived MSCs secreted more immune response-related proteins (interleukin 4, interferon-γ) than did the unactivated hUCB-derived MSCs.ConclusionThe data collected herein confirm for the first time that hUCB-derived MSCs, with or without activation, evidence significant cytotoxicity against human malignant glioma cells, and the immune response-related proteins secreted in this process may perform relevant functions.

Experience with pineal region tumors

Abstract The results are reported of a retrospective review of the presentation and outcome of 43 pineal region tumors treated from 1982 to 1996, including 20 identified tumors: 5 germinomas, 8 teratomas, 2 embryonal carcinomas, 1 endodermal sinus tumor, 2 pineocytomas and 2 pineoblastomas. Of the 43 tumors reviewed, 36 were located in the pineal region, 5 in the suprasellar, and 2 in both the pineal and suprasellar regions. Twenty patients underwent surgical resection: total in 6 and partial in 10, while only a biopsy was taken in 4 cases. Fifteen patients were managed on the basis of serum CSF tumor markers and radiation response. Twenty-three patients with germinomas received radiotherapy (RT) and had a 5-year survival rate of 87%. Fifteen patients with non-germinomatous germ cell tumors received RT and chemotherapy following direct surgery, and 5 died (mortality rate of 33.3%). The overall survival rate of the 43 patients with pineal tumors was 79.1% (34/43) and the death rate was 20.9% (9/43). It is now recognized that the wide variety of tumor types found in the pineal region necessitates different modes of treatment, and improved microsurgical and stereotactic surgical techniques have made mortality and morbidity rates acceptably low. Because the radiation response and CSF cytology are not enough to determine optimum treatment, a tissue diagnosis should be obtained in all patients.

Effect of Single Growth Factor and Growth Factor Combinations on Differentiation of Neural Stem Cells.

OBJECTIVEnThe effects on neural proliferation and differentiation of neural stem cells (NSC) of basic fibroblast growth factor-2 (bFGF), insulin growth factor-I (IGF-I), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) were assessed. Also, following combinations of various factors were investigated : bFGF+IGF-I, bFGF+BDNF, bFGF+NGF, IGF-I+BDNF, IGF-I+NGF, and BDNF+NGF.nnnMETHODSnIsolated NSC of Fisher 344 rats were cultured with individual growth factors, combinations of factors, and no growth factor (control) for 14 days. A proportion of neurons was analyzed using beta-tubulin III and NeuN as neural markers.nnnRESULTSnNeural differentiations in the presence of individual growth factors for beta-tubulin III-positive cells were : BDNF, 35.3%; IGF-I, 30.9%; bFGF, 18.1%; and NGF, 15.1%, and for NeuN-positive cells was : BDNF, 34.3%; bFGF, 32.2%; IGF-1, 26.6%; and NGF, 24.9%. However, neural differentiations in the absence of growth factor was only 2.6% for beta-tubulin III and 3.1% for NeuN. For beta-tubulin III-positive cells, neural differentiations were evident for the growth factor combinations as follows : bFGF+IGF-I, 73.1%; bFGF+NGF, 65.4%; bFGF+BDNF, 58.7%; BDNF+IGF-I, 52.2%; NGF+IGF-I, 40.6%; and BDNF+NGF, 40.0%. For NeuN-positive cells : bFGF+IGF-I, 81.9%; bFGF+NGF, 63.5%; bFGF+BDNF, 62.8%; NGF+IGF-I, 62.3%; BDNF+NGF, 56.3%; and BDNF+IGF-I, 46.0%. Significant differences in neural differentiation were evident for single growth factor and combination of growth factors respectively (p<0.05).nnnCONCLUSIONnCombinations of growth factors have an additive effect on neural differentiation. The most prominent neural differentiation results from growth factor combinations involving bFGF and IGF-I. These findings suggest that the combination of a mitogenic action of bFGF and postmitotic differentiation action of IGF-I synergistically affects neural proliferation and NSC differentiation.

Surgical results in pediatric moyamoya disease: angiographic revascularization and the clinical results.

OBJECTIVEnWe retrospectively reviewed the pediatric patients with moyamoya disease (MMD) who underwent bypass surgery at our institution to compare the surgical results according to the surgical procedures.nnnPATIENTS AND METHODSnThere were 24 total patients (age range: 2-15 years; mean age: 8.2 years). Twelve patients underwent encephalo-duro-arterio-synangiosis (EDAS) on 16 sides, 5 patients underwent encephalo-duro-arterio-myo-synangiosis (EDAMS) on 8 sides and 7 patients underwent combined superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis with EDAMS (STA-MCA-EDAMS) on 12 sides. The postoperative results were evaluated between 4 months and 5 years following surgery in terms of the angiographic revascularization and the clinical outcome.nnnRESULTSnEDAMS, regardless of the combined STA-MCA anastomosis, was significantly effective for achieving a good extent of the postoperative angiographic revascularization as compared with simple EDAS (P<0.05). STA-MCA-EDAMS tended to be better with respective to the relief of preoperative ischemic symptoms as compared with simple EDAS, although there was no significant statistical difference.nnnCONCLUSIONnThese results suggest that EDAMS with or without the combination of STA-MCA anastomosis was very useful for the formation of collateral circulation in comparison with simple EDAS for treating the pediatric patients with MMD, although these findings were not well correlated with the clinical outcomes.

Anterior Lumbar Interbody Fusion with Stand-Alone Interbody Cage in Treatment of Lumbar Intervertebral Foraminal Stenosis : Comparative Study of Two Different Types of Cages

OBJECTIVEnThis retrospective study was performed to evaluate the clinical and radiological results of anterior lumbar interbody fusion (ALIF) using two different stand-alone cages in the treatment of lumbar intervertebral foraminal stenosis (IFS).nnnMETHODSnA total of 28 patients who underwent ALIF at L5-S1 using stand-alone cage were studied [Stabilis(R) (Stryker, Kalamazoo, MI, USA); 13, SynFix-LR(R) (Synthes Bettlach, Switzerland); 15]. Mean follow-up period was 27.3 +/- 4.9 months. Visual analogue pain scale (VAS) and Oswestry disability index (ODI) were assessed. Radiologically, the change of disc height, intervertebral foraminal (IVF) height and width at the operated segment were measured, and fusion status was defined.nnnRESULTSnFinal mean VAS (back and leg) and ODI scores were significantly decreased from preoperative values (5.6 +/- 2.3 --> 2.3 +/- 2.2, 6.3 +/- 3.2 --> 1.6 +/- 1.6, and 53.7 +/- 18.6 --> 28.3 +/- 13.1, respectively), which were not different between the two devices groups. In Stabilis(R) group, postoperative immediately increased disc and IVF heights (10.09 +/- 4.15 mm --> 14.99 +/- 1.73 mm, 13.00 +/- 2.44 mm --> 16.28 +/- 2.23 mm, respectively) were gradually decreased, and finally returned to preoperative value (11.29 +/- 1.67 mm, 13.59 +/- 2.01 mm, respectively). In SynFix-LR(R) group, immediately increased disc and IVF heights (9.60 +/- 2.82 mm --> 15.61 +/- 0.62 mm, 14.01 +/- 2.53 mm --> 21.27 +/- 1.93 mm, respectively) were maintained until the last follow up (13.72 +/- 1.21 mm, 17.87 +/- 2.02 mm, respectively). The changes of IVF width of each group was minimal pre- and postoperatively. Solid arthrodesis was observed in 11 patients in Stabilis group (11/13, 84.6%) and 13 in SynFix-LR(R) group (13/15, 86.7%).nnnCONCLUSIONnALIF using stand-alone cage could assure good clinical results in the treatment of symptomatic lumbar IFS in the mid-term follow up. A degree of subsidence at the operated segment was different depending on the device type, which was higher in Stabilis(R) group.

Differential regulation of ciliary neurotrophic factor and its receptor in the rat hippocampus following transient global ischemia

To investigate a potential role of ciliary neurotrophic factor (CNTF) in transient global ischemia, we have studied the postischemic regulatory changes in the expression of CNTF and its receptor, the ligand-binding alpha-subunit (CNTFRalpha). Immunoblot analysis demonstrated CNTF levels were slightly upregulated already during the first day after ischemia and then increased markedly by more than 10-fold until 2 weeks postischemia. Immunoreactivity for CNTF became detectable 1 day after ischemia and was localized in reactive astrocytes. The intensity of the immunolabeling was maximal in CA1 during the phase of neuronal cell death (days 3-7 postischemia) and in the deafferented inner molecular layer of the dentate gyrus. Upregulation of CNTF expression was less pronounced in CA3 and absent in the stratum lacunosum moleculare and the outer molecular layer of the dentate gyrus and thus did not simply correlate with astroliosis as represented by upregulation of glial fibrillary acidic protein (GFAP). As shown by in situ hybridization, expression of CNTFRalpha mRNA was restricted to neurons of the pyramidal cell and granule cell layers in control animals. Following ischemia, reactive astrocytes, identified by double labeling with antibodies to GFAP, transiently expressed CNTFRalpha mRNA with a maximum around postischemic day 3. This astrocytic response was most pronounced in CA1 and in the hilar part of CA3. These results show that CNTF and its receptor are differentially regulated in activated astrocytes of the postischemic hippocampus, indicating that they are involved in the regulation of astrocytic responses and the neuronal reorganizations occurring after an ischemic insult.

Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model

PurposeHigh-grade gliomas are closely related to the mesenchymal phenotype which might be explained by unorthodox differentiation of glioma cancer stem cells (gCSCs). We reasoned that other non-neural stem cells, especially mesenchymal stem cells (MSCs), might play a role in expresssing mesenchymal phenotype of high-grade gliomas. Thus we hypothesized that cells resembling MSCs exist in glioma specimens.MethodsWe created a mouse (m) orthotopic glioma model using human gCSCs. Single-cell suspensions were isolated from glioma specimens and cultured according to the methods for mMSCs or gliomaspheres. These cells were analyzed by fluorescence-activated cell sorting (FACS) for surface markers associated with mMSCs or gCSCs. Glioma stroma (GS)-MSCs were exposed to mesenchymal differentiation conditions. To decide the location of GS-MSCs, sections of orthotopic glioma models were analyzed by immunofluorescent labeling.ResultsGS-MSCs were isolated which were morphologically similar to mMSCs. FACS analysis showed that the GS-MSCs had similar surface markers to mMSCs (stem cell antigen-1 [Sca-1]+, CD9+, CD45−, CD11b−, CD31−, and nerve/glial antigen 2 [NG2]−). GS-MSCs were capable of mesenchymal differentiation. Immunofluorescent labeling indicated that GS-MSCs are located around blood vessels, are distinct from endothelial cells, and have features that partially overlap with vascular pericytes.ConclusionsOur results indicate that cells similar to mMSCs exist in glioma specimens. The GS-MSCs might be located around vessels, which suggests that GS-MSCs may provide the mesenchymal elements of the vascular niche. GS-MSCs may represent non-neural stem cells that act as an important source of mesenchymal elements, particularly during the growth of gliomas.