The Stem Cell Potential of O-2A Lineage Astroglia.

Astrocytes are the most common glial type in the central nervous system. They play pivotal roles in neurophysiological and neuropathological processes. Mounting evidence indicates that astrocytes may act as neural stem cells and contribute to adult neurogenesis. In previous reports, freshly isolated O-2A progenitors were shown to revert to neural stem-like cells (NSLCs) when cultured with a serum-containing glial medium or bone morphogenic proteins for 3 days and with basic fibroblast growth factor consecutively. NSLCs possess self-renewal and multipotential capacities that can give rise to neurons and glial cells, which suggests that they have stem cell-like properties. However, the underlying molecular mechanisms and cell fate commitment when exposed to a neural conditioned medium remain obscure. In this study, we demonstrated that NSLCs grown in the serum-containing neurobasal medium can differentiate into induced neural-like cells (iNLCs). It was noteworthy that astroglia mixed in these cells, particularly in iNLCs, were gradually replaced by neural phenotypes during this glia-neuron conversion. Remarkably, these glial cells can maintain high levels of proliferation and self-renewal ability by activating the NF-κB and MAPK signals. Finally, we found that Notch, STAT3, autophagy, bHLH, and Wnt signals appear to be critical modulators of these intricate events. Altogether, these data demonstrate that O-2A lineage astroglia can function as neural stem cells and display neurogenic plasticity. Dissecting the regulatory pathways involved in these processes is essential to the understanding of glial cell fate and its precise functions. This finding may foster a better understanding of astrocytic heterogeneity and lead to innovative ways to readily apply stem-like astroglia cells as candidate cell sources for neural repair.

Engrafted primary type-2 astrocytes improve the recovery of the nigrostriatal pathway in a rat model of Parkinson's disease.

Parkinson's disease (PD) is a disorder characterized by a progressive loss of the dopaminergic neurons in the substantia nigra and a depletion of the neurotransmitter dopamine in the striatum. Our published results indicate that fasciculation and elongation protein zeta-1 (FEZ1) plays a role in the astrocyte-mediated protection of dopamine neurons and regulation of the neuronal microenvironment during the progression of PD. In this study, we examined the effects of engrafted type-2 astrocytes (T2As) with high expression of FEZ1 on the improvement of the symptoms and functional reconstruction of PD rats. T2As were stereotactically transplanted into the striatum of rats with PD induced by 6-hydroxydopamine (6-OHDA). An examination of apomorphine (APO)-induced rotations was performed to evaluate dopamine neuron damage and motor functions. Remarkably, the grafted cells survived in the lesion environment for six weeks or longer after implantation. In addition, the transplantation of T2As decrease the average velocity and the duration time of the APO-induced rotations, and increase the actuation time, as measured in the rotation behavioural tests. In the substantia nigra, the transplantation of T2As reduced the PD-induced GFAP, TH and FEZ1 downregulation. The grafted cells exclusively migrated to other regions near the injection site in the striatum and differentiated into GFAP+ astrocytes or TH+ neurons. Furthermore, by detecting monoamine neurotransmitters through high-performance liquid chromatography, we found that the nigrostriatal pathway had been repaired to some extent. Taken together, these results suggest that engrafted T2As with high expression of FEZ1 improved the symptoms and functional reconstruction of PD rats, providing a theoretical basis for FEZ1 as a potential target and engraftment of T2As as a therapeutic strategy in the treatment of PD.

Applied anatomical study of the modified anconeus flap approach.

PURPOSE: Conventional surgical therapy for an intercondylar humerus fracture might result in multiple potential complications. Our study was conducted to evaluate the modified anconeus flap approach by adequately exposing the distal humeral articular surface, avoiding osteotomy of the olecranon and transection of the main part of the triceps brachial tendon from the olecranon. METHODS: Preparations of 20 upper limb specimens from adult cadavers were used in this study. We investigated the anatomical features of the distal tendon of the triceps brachii. Then, we designed a modified anconeus flap approach in cadaver specimens combined with the medial paratricipital approach, and we compared the extent of exposure of the distal humeral articular surface between the triceps-reflecting anconeus pedicle approach and this modified approach. RESULTS: The downward neurovascular bundles supplying the anconeus were located far from the intramuscular tendon of the triceps brachii. In addition, the medial head of the triceps was continuous with the anconeus near the lateral epicondyle of the humerus. These anatomical properties could assist in reducing adverse events in surgery. The percentage of the exposed humerus distal articular surface was 42.7% by applying the modified anconeus flap approach combined with the medial paratricipital approach. The modified anconeus flap approach can overcome the shortcomings of osteotomy or triceps transverse and fulfill reduction and internal fixation of most distal humerus intercondylar fractures. CONCLUSIONS: The present study has demonstrated a new approach for adequately exposing the distal humeral articular surface during surgery for an intercondylar humerus fracture. With this modified approach, osteotomy of the olecranon and the separation or transection of the main part of the triceps brachial tendon from the olecranon are not necessarily required. Therefore, we suggest that this novel approach could be applied as the primary surgical approach in intercondylar humerus fracture surgeries if the surgeons are familiar with the regional features of distal tendon of the triceps brachii and anconeus.

Expression pattern of transcription factor SOX2 in reprogrammed oligodendrocyte precursor cells and microglias: Implications for glial neurogenesis.

Oligodendrocyte Precursor Cells (OPCs) can revert to multipotential Neural Stem-Like Cells (NSLCs) which can self-renew and give rise to neurons, astrocytes and oligodendrocytes when exposed to certain extracellular signals. This is a significant progress to understand developmental neurobiology, in particularly the possibility of converting glia to stem cells for the treatment of neurological disorders. Similarly, recent findings revealed that brain-resident microglias (MGs) can be converted to multipotential state through de-differentiation. In this study, we investigated the role of SRY (sex-determining region)-box 2 (SOX2), a high-mobility group DNA binding domain transcription factor, in the reprogramming of OPCs and MGs and molecular pathways involved in these process. Immunocytochemical analyses demonstrated that expression of SOX2 was upregulated in the reprogrammed MGs and OPCs as well as other neural stem cell markers such as CD15 and nestin. Western blot and double immunostaining analyses further confirmed that activation of bone morphogenetic proteins (BMPs) signaling partnering with SOX2 might be one of the molecular pathways involved in lineage reprogramming of OPCs which is also true in the reversion of MGs. Taken together, these results indicated that lineage reprogramming of OPCs and MGs are both controlled by the same signaling pathway and glia can be reprogrammed in culture by inducing expression of neurogenic transcription factors to transgress their lineage restriction and can stably acquire a neuronal identity. Our results suggested innovative perspectives for cell therapy with glia cells.

Anatomical study of the communicating branches of cords of the brachial plexus and their clinical implications.

The aim of this study was to investigate the occurrence and patterns of the communicating branches of cords of the brachial plexus (BPs). This study was performed with 50 fixed adult cadavers (all 100 sides). The BPs were exposed, the presence of the communicating branches of BPs were determined, measured, and photographed. The communicating branches were identified in 27 sides of the BPs. According to enthesis, the communicating branches between the medial and lateral cords (25 sides) were divided into five types. The most common branches connected the lateral cord with the medial root of the median nerve (16 sides). All the communicating branches between the lateral and medial cords obliquely crossed anterior to the axillary artery and passed below the thoracoacromial artery trunk. The distance of the communicating branch with the origin of thoracoacromial artery trunk was 1.60 ± 0.64 cm. The length, transverse diameter, and anteroposterior diameter of communicating branch were 1.67 ± 0.62 cm, 1.77 ± 0.63 mm, and 1.91 ± 0.34 mm, respectively. These anatomical data about the communicating branches will be helpful for surgeons who perform surgical procedures in the cervical and axillary regions.

Anatomical study and clinical significance of the rami communicantes between cervicothoracic ganglion and brachial plexus.

The aim of this study was to provide a detailed characterization of the rami communicantes between the stellate (or cervicothoraic) ganglion (CTG) and brachial plexus (BP). Rami communicantes of 33 fixed adult cadavers were macroscopically observed, and connection between CTG and spinal nerves and branching was investigated. In all cases, except one, the hibateral medial rami communicantes was found to be positioned symmetrically between the CTG and C7, C8 spinal nerves. Gray rami communicantes arising from the CTG joined C8, C7, C6 nerve roots on 66, 63, and 6 sides, respectively, and branched from the rami communicantes to C7, C6, C5 nerve roots lying on 51, 41, and 2 sides, respectively. Forty-five sides of the branches from rami communicantes derived from CTG to C8 were observed to ascend through the transverse foramina of the C7 nerve. The branches from rami communicantes derived from CTG to C7 to the C6 nerve were observed ascending through the foramen transversarium of the six cervical vertebrae along with the vertebral artery and joining the C6 spinal nerve in 41 sides. Knowledge about the general distribution and individual variations of the rami communicantes between CTG and BP will be useful toward studies involving the inference of sympathetic nerve stimulation of the upper limbs and could be important for surgeons who perform surgical procedures in the cervical region or medical blockade of nerve fibers.

A2B5 lineages of human astrocytic tumors and their recurrence.

Astrocytomas are very common intracranial glial cell neoplasms with an inherent tendency to progress. However, the heterogeneity of the morphological features and clinical behavior of the tumors makes accurate prognosis based on the histopathological grading system very difficult. Studies demonstrated that astrocytes have two distinctive cell lineages, and tumors arisen from these two astrocytic lineages have been speculated to have different biological and clinical manifestations. The present study aimed to delineate these two astrocytic lineages in human astrocytomas by using different immunohistochemical markers and to correlate the cell lineages of the tumors with their recurrence. Three markers were used, namely the A2B5 antigen, which is present in type 2 astrocytes but absent in type 1 astrocytes, glial fibrillary acidic protein (GFAP), a marker for astrocytes, and galactocerebroside (GC), a marker for oligodendrocytes. It was found that astrocytomas sharing the A2B5+ lineage (A2B5 positive and GFAP positive) have a significantly higher recurrence rate than the tumors of the A2B5- lineage (A2B5 negative and GFAP positive). Immunohistochemical staining and PCR-single-stranded conformational polymorphism analysis showed that p53 overexpression and p53 mutations were closely associated with the recurrent astrocytomas, and p53 abnormalities were more frequently detected in astrocytomas of the A2B5+ lineage. Quantification of proliferation by counting argyrophil nucleolar organizer regions (AgNORs) indicated a higher AgNOR count in the A2B5+ lineage than the A2B5- lineage. Our findings thus suggest that astrocytomas share similar antigenicity with astrocytes, and that the A2B5+ lineage exhibited a higher recurrence rate than the A2B5- lineage. The higher recurrence rate of the A2B5+ tumors may be in part related to the higher frequency of p53 abnormalities found in the tumors and the higher proliferative activity as reflected by the higher AgNOR count of the tumors.

Differential expression of S100 proteins in the developing human hippocampus and temporal cortex.

S100 calcium binding proteins have long been known to express in the adult nervous system, but their distribution in the developing brain, especially the human fetal brain, is largely unknown. We used an immunohistochemical method to determine the expression of three S100 proteins, namely S100A4, S100A5, and S100A13, in the human fetal hippocampus and temporal cortex from 12 to 33 weeks of gestation. At 12 weeks, S100A5 was strongly expressed in the cells and fibers of the polymorphic, pyramidal, and molecular layers of the hippocampus. Thereafter, its expression decreased with age. In the temporal cortex, S100A5 expression was detected from 12 weeks onwards, peaked at 20 to 24 weeks, and then decreased with age. The horizontal fibers of the marginal zone were immunoreactive at all stages examined. S100A13 immunoreactivity was also detected in both cells and fibers of the hippocampus at 12 weeks, became slightly stronger at 20 weeks, and then decreased with age. In the temporal cortex, S100A13 immunoreactivity was also strong in all cellular layers at 12 to 24 weeks before it declined with age from 28 weeks onwards. Among the three proteins examined, S100A4 showed the weakest expression, which was detected in the cells and fibers of the hippocampus and the temporal cortex at all stages examined. Our results have demonstrated for the first time, in the human fetal hippocampus and temporal cortex, specific spatio-temporal patterns of expression of these proteins, all of which are likely to have different roles to play during development despite their pronounced sequence homology.