Spatiotemporal expression of Nogo-66 receptor after focal cerebral ischemia.

NgR, the receptor for the neurite outgrowth inhibitor Nogo-66, plays a critical role in the plasticity and regeneration of the nervous system after injury such as ischemic stroke. In the present study, we used immunohistochemistry to investigate the regional expression of NgR in rat brain following middle cerebral artery occlusion (MCAO). NgR protein expression was not observed in the center of the lesion, but was elevated in the marginal zone compared with control and sham-operated rats. The cerebral cortex and hippocampus (CA1, CA2, and CA3) showed the greatest expression of NgR. Furthermore, NgR expression was higher in the ipsilesional hemisphere than on the control side in the same coronal section. Although time-dependent changes in NgR expression across brain regions had their own characteristics, the overall trend complied with the following rules: NgR expression changes with time showed two peaks and one trough; the first peak in expression appeared between 1 and 3 days after MCAO; expression declined at 5 days; and the second peak occurred at 28 days.

Involvement of phospholipase C-γ in the pro-survival role of glial cell line-derived neurotrophic factor in developing motoneurons in rat spinal cords.

The glial cell line-derived neurotrophic factor (GDNF) has been proven to be the most powerful neurotrophic factor in neuronal development. However, it remains uncertain as to which intracellular signaling pathway interacting with GDNF is invovlved in motoneuron (MN) development. In this study, we investigated whether phosphoinositide phospholipase C-γ (PLC-γ) is involved in GDNF-promoted MN development. The primary spinal MNs from 12- to 14-day-old embryos of Sprague-Dawley rats were cultured and survival was sustained by GDNF. A specific inhibitor of PLC-γ, 1-[6-((17b-3-methoxyestra-1,3,5(10)-trien-17-yl) amino)hexyl]-1H-pyrrole-2,5-dione (U73122), was used to block the pro-survival effect of GDNF. Our results showed that MN-like cells appeared at 72 h after initial implantation and were sustained for a period of up to seven days under GDNF treatment. These cultured MNs expressed neuron-specific enolase, SMI-32, 75-kDa low-affinity neurotrophic receptor and choline acetyltransferase. The survival rate of the cultured MNs at 24 h was significantly lower in the GDNF + U73122-treated group (31.87±2.17%), compared either with that of the GDNF- (81.38±1.13%) or GDNF + DMSO (79.39±1.22%)-treated groups. The present data suggest that PLC-γ may be one of the intracellular signals that play a role in the survival-promoting effects of GDNF in developing spinal MNs.

[Surgical anatomy of totally trans-oral video-assisted thyroidectomy].

OBJECTIVE: To define the anatomical approach, anatomical planes and related vessels and nerves to create a safe and reproducible combined sublingual and bi-vestibular access for trans-oral video-assisted thyroidectomy. METHODS: From November 2009 to May 2011, twenty-five embalmed human specimens were dissected for anatomical information of the cervical region, the mandible region and the supra-hyoid muscles. On twenty fresh frozen human specimens after an experimental trans-oral endoscopic thyroidectomy, the related vascular, neural structures and muscles were evaluated. RESULTS: The optical access port was placed in the midline sublingual. The geniohyoid muscle, mylohyoid muscle and the anterior belly of the digastric muscle were divided in the midline in order to reach the plane under the platysma muscle. The mucosa was sagittal incised bilaterally in the vestibular of oral cavity for working trocar, at the level of the first molar of the mandible. The working trocar reached directly the periosteum of the mandible, under the facial vessel and the marginal branch of facial nerve, and then passed below the platysma muscle into the infra-laryngeal working area. The distance from mental nerve to mandibular midline and between mental nerve and facial artery were (25.8 ± 0.9) mm and (29.4 ± 0.9) mm respectively. Anatomical dissections showed that after an experimental trans-oral combined sublingual and bi-vestibular access, all muscles of the floor of the oral cavity as well as the related vascular and neural structures are intact. The maximum nodule size of the resected specimens in the totally trans-oral approach was up to 50 mm. CONCLUSION: The combined sublingual and bi-vestibular access of trans-oral video-assisted thyroidectomy is safe and reproducible.

Direct intrahepatic portocaval shunt through transhepatic puncture via retrohepatic inferior vena cava: applied anatomical study.

BACKGROUND: DIPS is to create a portosystemic shunt directly between the portal vein and the retrohepatic inferior vena cava (RIVC) without passing through the hepatic vein. It has been recommended that the DIPS could be applied when routine TIPS is unsuccessful or the patient has anatomical variations of the hepatic vein. The aim of this study was to identify the safe area of the RIVC where the DIPS can be safely established. MATERIALS AND METHODS: The lengths of the safe and unsafe areas of the RIVC were measured. The tributaries of the RIVC were examined. The diameter of these tributaries was measured and their incidence and relation to the safe area of the RIVC were observed. The puncture distances of DIPS and TIPS were measured and compared. RESULTS: The liver together with the RIVC was collected from 31 adult cadavers (age 32-65 years; M/F 25/6). 1. The safe and unsafe areas of the RIVC: the total length of the RIVC was 70.1 +/- 13.0 mm (33.1-92.0 mm), whereas the length of the safe area of the RIVC was 54.3 +/- 12.3 mm (20.2-71.1 mm), which was about over 70% of the total length. The length of the unsafe area at the upper end was 5.9 +/- 1.8 mm (3.0-10.2 mm), and at the lower end was 8.9 +/- 2.9 mm (3.1-20.0 mm). 2. The tributaries of the RIVC: In about 90% of the cadavers (90.3%; 28 out of 31), the LHV and MHV had the common trunk. The other three cadavers (9.7%; 3 out of 31) had independent RHV, MHV and LHV. There were 217 of small hepatic veins draining into the lower segment of the RIVC. Over 70% of the small hepatic veins were smaller than 5 mm in diameter and distributed on the anterior and left wall of the lower RIVC. 3. Puncture distances of the DIPS and TIPS: The distances from the bifurcation of the portal vein to the RIVC, to the right and to middle hepatic veins were 31.2 +/- 7.9 mm (15.0-47.2 mm), 38.6 +/- 8.1 mm (17.2-59.0 mm), and 46.6 +/- 8.2 mm (34.0-68.1 mm), respectively. Thus, the puncture distances via the RIVC, RHV and LHV were significantly different (P < 0.001). The puncture distance of the DIPS was shortest. CONCLUSION: Anatomically, DIPS is a feasible interventional procedure to make a intrahepatic shunt between IVC and portal vein directly, and has its anatomical advantages compared to TIPS.

ZM 447439 inhibition of aurora kinase induces Hep2 cancer cell apoptosis in three-dimensional culture.

Mitotic Aurora kinases are essential for accurate chromosome segregation during cell division. Forced overexpression of Aurora kinase results in centrosome amplification and multipolar spindles, causing aneuploidy, a hallmark of cancer. ZM447439 (ZM), an Aurora selective ATP-competitive inhibitor, interferes with the spindle integrity checkpoint and chromosome segregation. Here, we showed that inhibition of Aurora kinase by ZM reduced histone H3 phosphorylation at Ser10 in Hep2 carcinoma cells. Multipolar spindles were induced in these ZM-treated G(2)/M-arrested cells with accumulation of 4N/8N DNA, similar to cells with genetically suppressed Aurora-B. Cells subsequently underwent apoptosis, as assessed by cleavage of critical apoptotic associated protein PARP. Hep2 cells formed a tumor-like cell mass in 3-dimensional matrix culture; inhibition of Aurora kinase by ZM either destructed the preformed cell mass or prevented its formation, by inducing apoptotic cell death as stained for cleaved caspase-3. Lastly, ZM inhibition of Aurora kinase was potently in association with decrease of Akt phosphorylation at Ser473 and its substrates GSK3alpha/beta phosphorylation at Ser21 and Ser9. Together, we demonstrated that Aurora kinase served as a potential molecular target of ZM for more selective therapeutic cancer treatment.