Akira Hakuba, Masaki Komiyama, Takeshi Tsujimoto, Myung Soo Ahn, Shuro Nishimura, Tomio Ohta and Hideki Kitano
✓ A combined anterior and lateral approach to the anterior cervical spinal canal with fusion was performed on five patients with cervical dumbbell-shaped tumors. The procedure consists of anterior discectomy and ipsilateral uncectomy, and removal of the posterolateral corners and posterior transverse ridges of the upper and lower vertebral bodies at the level of the tumor. In the case of a large tumor in the spinal canal, additional removal of a limited segment from the lateral part of the vertebral body was performed. The bone defect was filled with a T-shaped iliac bone graft. Two vertebral bodies were fused in each case. The highest level of the operation was C-2 and the lowest was T-1. The authors believe that any cervical dumbbell-shaped tumor below the C-2 level can be removed via an anterolateral approach as long as no more than three levels of the spine are involved.
Yasushi Takagi, Masaki Nishimura, Asuka Morizane, Jun Takahashi, Kazuhiko Nozaki, Junya Hayashi and Nobuo Hashimoto
Object. Cell replacement therapy including the use of embryonic stem cells (ESCs) may represent a novel treatment for damage from stroke. In this study, the authors transplanted neural progenitor cells (NPCs) derived from ESCs into ischemic brain and analyzed their survival and differentiation.
Methods. Multipotential NPCs were generated from ESCs by using the stromal cell—derived inducing activity method. These cells could differentiate in vitro into neurons, glia, and oligodendrocytes, thus revealing them to be neural stem cells. The NPCs were then transplanted into ischemic brain. At 2 weeks postischemia, the transplanted cells occupied 18.8 ± 2.5% of the hemispheric area; by 4 weeks postischemia, 26.5 ± 4% of the hemisphere. At 4 weeks after transplantation, green fluorescent protein (GFP)—positive transplanted cells showed mature neuronal morphological features. The authors also investigated the expression of differentiation markers and various neurotransmitters. Transplanted cells were immunopositive for neuronal nuclei, β-tubulin-III, and glial fibrillary acidic protein. Of the GFP-positive cells, 33.3 ± 11.5% were positive for glutamate decarboxylase, 13.3 ± 5.8% for glutamate, 2.1 ± 2.5% for tyrosine hydroxylase, 1.8 ± 2% for serotonin, and 0.4 ± 0.2% for choline acetyltransferase.
Conclusions. The authors confirmed the survival and differentiation of ESC-derived NPCs transplanted into the ischemic brain. Surviving transplanted cells expressed several neural markers and neurotransmitters. These findings indicate that these cells can function in the brain.
Tomohiro Aoki, Masaki Nishimura, Ryota Ishibashi, Hiroharu Kataoka, Yasushi Takagi and Nobuo Hashimoto
The pathophysiological origin of cerebral aneurysms is closely associated with chronic inflammation in arterial walls. Recently, the authors identified nuclear factor–kappa B (NF-κB) as a key mediator of cerebral aneurysm formation and progression. Because Toll-like receptor 4 (TLR4) stimulates NF-κB activation in arterial walls in atherosclerosis, the authors hypothesize that TLR4 expresses in cerebral aneurysms and contributes to the activation of NF-κB in cerebral aneurysm walls.
Cerebral aneurysms were induced in male Sprague-Dawley rats. Expression of TLRs in cerebral aneurysm walls was assessed using reverse transcriptase polymerase chain reaction (RT-PCR). The expression of TLR4 was examined using RT-PCR, immunohistochemical studies, and Western blotting. To assess TLR4 dependency on NF-κB activation, double immunostaining and a study using NF-κB–deficient mice were done. Finally, TLR4 expression in human cerebral aneurysm walls was assessed using immunohistochemical studies.
In cerebral aneurysm walls, TLR1, -4, -5, -6, -10, and -11 were expressed. Among them, TLR4 and TLR10 expression changed during cerebral aneurysm formation. Expression of TLR4 was predominantly in the endothelial cell layer of cerebral aneurysm walls, and was transitionally upregulated at the early stage of cerebral aneurysm formation. The TLR4 expression coincided well with NF-κB activation. In human cerebral aneurysms, TLR4 was also expressed in the endothelial cell layer, as it was in rats.
Toll-like receptor 4 was expressed in cerebral aneurysm walls both in rats and humans. This receptor may play a crucial role in cerebral aneurysm formation through NF-κB activation in endothelial cells. The results of the present study will shed new light on the pathogenesis of cerebral aneurysm formation.