Schwann Cells Transplantation Promoted and the Repair of Brain Stem Injury in Rats

Objective To explore the possibility of Schwann cells transplantation to promote the repair of injured brain stem reticular structure in rats. Methods Schwann cells originated from sciatic nerves of 1 to 2-day-old rats were expanded and labelled by BrdU in vitro, transplanted into rat brain stem reticular structure that was pre-injured by electric needle stimulus. Immunohistochemistry and myelin-staining were used to investigate the expression of BrdU, GAP-43 and new myelination respectively. Results BrdU positive cells could be identified for up to 8 months and their number increased by about 23%, which mainly migrated toward injured ipsilateral cortex. The GAP-43 expression reached its peak in 1 month after transplantation and was significantly higher than that in the control group. New myelination could be seen in destructed brain stem areas. Conclusion The transplantation of Schwann cells can promote the restoration of injured brain stem reticular structure.

ERBB1 Is Amplified and Overexpressed in High-grade Diffusely Infiltrative Pediatric Brain Stem Glioma

PURPOSE:This study was conducted to investigate the incidence of ERBB1 amplification and overexpression in samples of diffusely infiltrative (WHO grades Ⅱ-Ⅳ) pediatric brain stem glioma (BSG) and determine the relationship of these abnormalities to expression and mutation of TP53 and tumor grade. Experimental Design: After central pathology review, the incidence of ERBB1 amplification and overexpression was determined in 28 samples (18 surgical biopsy and 10 postmortem specimens) of BSG using quantitative PCR and immunohistochemistry,

Effect of Acupuncture on the Auditory Evoked Brain Stem Potential in Parkinson's Disease

Under the auditory evoked brain stem potential (ABP) examination, the latent period of V wave and the intermittent periods of III-V peak and I-V peak were significantly shortened in Parkinson's disease patients of the treatment group (N=29) after acupuncture treatment. The difference of cumulative scores in Webster's scale was also decreased in correlation analysis. The increase of dopamine in the brain and the excitability of the dopamine neurons may contribute to the therapeutic effects, in TCM terms, of subduing the pathogenic wind and tranquilizing the mind.……

Clinicopathological features and treatment outcomes of brain stem gliomas in Saudi population

AIM: To analyze experiences to identify treatment outcomes and prognostic factors in a Saudi population.METHODS: Medical records of patients with brainstem gliomas treated from July 2001 to December 2012 were reviewed to identify treatment outcomes of surgery, radiation therapy and chemotherapy and associated prognostic factors in a Saudi population.RESULTS: We analyzed 49 brain stem glioma(BSG) patients from July 2001 to December 2012; 31 of them were males(63.3%) with a median age of 12.6 years(range: 8-64 mo). Twenty-two patients(44.9%) had diffuse intrinsic pontine gliomas(DIPG) and 15(30.6%) presented with focal/tectal BSG. Histopathology was available in 30 patients(61.2%). Median survival time for the whole cohort was 1.5 years. One and two year OS rates were 51.1% and 41.9% respectively. Two year OS rates for focal/tectal, dorsally exophytic, cervicomedullary and DIPG tumors were 60%, 33.3%, 33.3% and 13.6% respectively(P < 0.0001). Significant prognostic factors related to OS were age at diagnosis(worse for > 18 years) P = 0.01, KPS < 70 P = 0.02, duration of symptoms(< 60 d) P = 0.002, histology(better for favorable) P = 0.002, surgery(maximal resection) P = 0.002, and concurrent chemotherapy with radiation therapy in DIPG(better if given) P = 0.01.CONCLUSION: BSG, especially the DIPG subgroup, had a dismal prognosis, needing more aggressive neurosurgical, radiation and chemotherapy techniques, while focal and tectal tumors were found to have a better prognosis.

Electro-Acupuncture for Treatment of Dysequillibrium Due to Cerebellum or Brain Stem Infarction

The authors treated 26 cases of dysequillibrium due tocerebellum or brain stem infarction byelectro-acupuncture from Aug 2000 - April 2002. Theresults were quite satisfactory and reported as follows.

Hypertensive brain stem encephalopathy with pontine hemorrhage: A case report

Hypertensive brain stem encephalopathy(HBE) is a rare, under diagnosed subtype of hypertensive encephalopathy(HE) which is usually reversible, but with a potentially fatal outcome if hypertension is not managed promptly. To the best of our knowledge, only one case of HE with brain stem hemorrhage has been reported. We report a case of HBE with pontine hemorrhage in a 36-year-old male patient. The patient developed severe arterial hypertension associated with initial computed tomography showing the left basilar part of pons hemorrhage, fluid-attenuated inversion-recovery showing hyperintense signals in the pons and bilateral periventricular, anterior part of bilateral centrum ovale. The characteristic clinical findings were walking difficulty, right leg weakness, and mild headache with nausea which corresponded to the lesions of MR imagings. The lesions improved gradually with improvements in hypertension, which suggested that edema could be the principal cause of the unusual hyperintensity on magnetic resonance images.

Stroke-like onset of brain stem degeneration presents with unique MRI sign and heterozygous NMNAT2 variant:a case report

Background:Acute-onset neurodegenerative diseases in older patients are rare clinical cases,especially when the degeneration only affects specific regions of the nervous system.Several neurological disorders have been described in which the degeneration of brain parenchyma originates from and/or primarily affects the brain stem.Clinical diagnosis in these patients,however,is often complicated due to a poor understanding of these diseases and their underlying mechanisms.Case presentation:In this manuscript we report on a 73-year-old female who had experienced a sudden onset of complex neurological symptoms that progressively worsened over a period of 2 years.Original evaluation had suggested a MRI-negative stroke as underlying pathogenesis.The combination of patient’s medical history,clinical examination and exceptional pattern of brain stem degeneration presenting as“kissing swan sign”in MR imaging was strongly suggestive of acute onset of Alexander’s disease.This leukoencephalopathy is caused by GFAP(glial fibrilary acidic protein)gene mutations and may present with brain stem atrophy and stroke-like onset of symptoms in elderly individuals.However,a pathognomonic GFAP gene mutation could not be identified by Sanger sequencing.Conclusions:After an extended differential diagnosis and exclusion of other diseases,a definite diagnosis of the patient’s condition presently remains elusive.However,whole-exome sequencing performed from patient’s blood revealed 12 potentially disease-causative heterozygous variants,amongst which several have been associated with neurological disorders in vitro and in vivo–in particular the axon degeneration-related NMNAT2 gene.

Imaging the structure and organization of mouse cerebellum and brain stem with second harmonic generation microscopy

To visualize the structure and organization of the brain is a fundamental requirement in the research of neuroscience. Here, combining with two-photon excitation fluorescence microscopy and transgenetic mouse GAD67,we demonstrate a custom-built second harmonic generation（SHG） microscope to discriminate brain layers and sub regions in the cerebellum and brain stem slices with cellular resolution. In particular, the cell densities of neurons in different brain layers are extracted due to the cell soma appearing as dark shadow on an SHG image.Further, the axon initial segments of the Purkinje cell are easily recognized without labeling, which would be useful for guiding micropipettes for electrophysiology.

Adult Bone Marrow Cells Can Be Converted into Brain Stem Cells for Transplantation

骨髓细胞移植入大脑后,不仅可在脑内继续存活,还会自行转换成大脑 传递神经脉冲的神经细胞,而且完全不会引发任何问题。这显示人体具有的自 行愈合功能会自动替代损坏的大脑细胞,这是人类过去未曾发现的。

Differentiation profile of brain tumor stem cells:a comparative study with neural stem cells

大脑肿瘤干细胞(BTSC ) 的区别侧面的理解，在肿瘤房间人口之中的关键的，将通过有神经干细胞(NSC ) 的比较借卓见进 glioma 的起源并且最终产出新途径与这难处理的疾病作斗争。这里，我们从外科的 glioma 标本的有教养、净化的 BTSC 和 NSCsfrom 人的胎儿的大脑织物，并且进一步分析了他们的细胞的生物行为，他们的特别区别性质。是期望，区分进成熟神经显型的 NSC。然而， BTSC 展出了的 Inthe 一样的区别状况区分了差别。词法上，房间变得变平并且属于第一个星期，但是逐渐地此后聚集了并且改过漂浮的肿瘤范围。在相应时期期间，无差别的房间标记 CD133 和巢在的表示率在 BTSC 不停地减少，但是 1 个星期以后，他们重获上升趋势。有趣地，区分的房间标记 GFAP 和 beta-tubulinIIIshowed 表示变化逆到无差别的房间标记的。总起来说， BTSCswere 揭示了拥有一个能力抵抗区别，它实际上代表 glioma 的恶意的行为。

Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models

Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are still unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models （c-myc/SV40Tag＋/Tet-on＋） to explore the malignant trans- formation potential of neural stem cells by observing the differences of neural stem cells and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain tumor stem cells. The numbers of cytolysosomes and autophagosomes in brain tumor stem cells and induced neural stem cells were lower and the proliferative activity was obviously stronger than that in normal neural stem cells. Normal neural stem cells could differentiate into glial fibrillary acidic protein-positive and microtubule associated protein-2-positive cells, which were also negative for nestin. However, glial fibrillary acidic protein/nestin, microtubule associated protein-2/nestin, and glial fibrillary acidic protein/microtubule associated protein-2 double-positive cells were found in induced neural stem cells and brain tumor stem cells. Results indicate that induced neural stem cells are similar to brain tumor stem cells, and are possibly the source of brain tumor stem cells.

Isolation,cultivation and identification of brain glioma stem cells by magnetic bead sorting

This study describes a detailed process for obtaining brain glioma stem cells from freshly dissected human brain glioma samples using an immunomagnetic bead technique combined with serum-free media pressure screening. Furthermore, the proliferation, differentiation and self-renewal biological features of brain glioma stem cells were identified. Results showed that a small number of CD133 positive tumor cells isolated from brain glioma samples survived as a cell suspension in serum-free media and proliferated. Subcultured CD133 positive cells maintained a potent self-renewal and proliferative ability, and expressed the stem cell-specific markers CD133 and nestin. After incubation with fetal bovine serum, the number of glial fibrillary acidic protein and microtubule associated protein 2 positive cells increased significantly, indicating that the cultured brain glioma stem cells can differentiate into astrocytes and neurons. Western blot analysis showed that tumor suppressor phosphatase and tensin homolog was highly expressed in tumor spheres compared with the differentiated tumor cells. These experimental findings indicate that the immunomagnetic beads technique is a useful method to obtain brain glioma stem cells from human brain tumors.

Collagen-chitosan scaffold impregnated with bone marrow mesenchymal stem cells for treatment of traumatic brain injury

Combinations of biomaterials and cells can effectively target delivery of cells or other therapeutic factors to the brain to rebuild damaged nerve pathways after brain injury.Porous collagen-chitosan scaffolds were prepared by a freeze-drying method based on brain tissue engineering.The scaffolds were impregnated with rat bone marrow mesenchymal stem cells.A traumatic brain injury rat model was established using the 300 g weight free fall impact method.Bone marrow mesenchymal stem cells/collagen-chitosan scaffolds were implanted into the injured brain.Modified neurological severity scores were used to assess the recovery of neurological function.The Morris water maze was employed to determine spatial learning and memory abilities.Hematoxylin-eosin staining was performed to measure pathological changes in brain tissue.Immunohistochemistry was performed for vascular endothelial growth factor and for 5-bromo-2-deoxyuridine(BrdU)/neuron specific enolase and BrdU/glial fibrillary acidic protein.Our results demonstrated that the transplantation of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds to traumatic brain injury rats remarkably reduced modified neurological severity scores,shortened the average latency of the Morris water maze,increased the number of platform crossings,diminished the degeneration of damaged brain tissue,and increased the positive reaction of vascular endothelial growth factor in the transplantation and surrounding areas.At 14 days after transplantation,increased BrdU/glial fibrillary acidic protein expression and decreased BrdU/neuron specific enolase expression were observed in bone marrow mesenchymal stem cells in the injured area.The therapeutic effect of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds was superior to stereotactic injection of bone marrow mesenchymal stem cells alone.To test the biocompatibility and immunogenicity of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds,immunosuppressive cyclosporine was intravenously injected 12 hours before transplantation and 1-5 days after transplantation.The above indicators were similar to those of rats treated with bone marrow mesenchymal stem cells and collagen-chitosan scaffolds only.These findings indicate that transplantation of bone marrow mesenchymal stem cells in a collagen-chitosan scaffold can promote the recovery of neuropathological injury in rats with traumatic brain injury.This approach has the potential to be developed as a treatment for traumatic brain injury in humans.All experimental procedures were approved by the Institutional Animal Investigation Committee of Capital Medical University,China(approval No.AEEI-2015-035)in December 2015.

Transplantation of autologous bone marrow-derived mesenchymal stem cells for traumatic brain injury

Results from the present study demonstrated that transplantation of autologous bone marrow-derived mesenchymal stem cells into the lesion site in rat brain significantly ameliorated brain tissue pathological changes and brain edema, attenuated glial cell proliferation, and increased brain-derived neurotrophic factor expression. In addition, the number of cells double-labeled for 5-bromodeoxyuridine/glial fibrillary acidic protein and cells expressing nestin increased. Finally, blood vessels were newly generated, and the rats exhibited improved motor and cognitive functions. These results suggested that transplantation of autologous bone marrow-derived mesenchymal stem cells promoted brain remodeling and improved neurological functions following traumatic brain injury.

Umbilical cord-derived mesenchymal stem cell transplantation combined with hyperbaric oxygen treatment for repair of traumatic brain injury

Transplantation of umbilical cord-derived mesenchymal stem cells（UC-MSCs） for repair of traumatic brain injury has been used in the clinic. Hyperbaric oxygen（HBO） treatment has long been widely used as an adjunctive therapy for treating traumatic brain injury. UC-MSC transplantation combined with HBO treatment is expected to yield better therapeutic effects on traumatic brain injury. In this study, we established rat models of severe traumatic brain injury by pressurized fluid（2.5–3.0 atm impact force）. The injured rats were then administered UC-MSC transplantation via the tail vein in combination with HBO treatment. Compared with monotherapy, aquaporin 4 expression decreased in the injured rat brain, but growth-associated protein-43 expression, calaxon-like structures, and CM-Dil-positive cell number increased. Following combination therapy, however, rat cognitive and neurological function significantly improved. UC-MSC transplantation combined with HBO therapyfor repair of traumatic brain injury shows better therapeutic effects than monotherapy and significantly promotes recovery of neurological functions.

Sudden Death due to Brainstem Leukemic Hemorrhage： A Case Report

Introduction Leukem ia is a hem atologic neoplasm characterized by potential infectious and hem orrhagic com plications In adult patients with acute leukem ia,in fection is the most com m on com plication.Imtrcra nial hem orrhage (ICH) is the second most common com plication.H ow ever,ICH has been identified as the m ajor cause of m orbidity and m ortaliity in pa tients with leukem ia[1-6].A num ber of case ceports ascribed the death of leukem ic patients due to hem orrhge of the supratentorial and infratentorial brain,basal ganglia,and cerebellum [2,7-9].However,few cases have reported on brainstem hem orrhage.The current case report involved a young wom an who died of brainstem hem orrhage due to acute leukem ia,discussing the pathophysiologic m echanism underly ing ICH.Futhherm ore,the risk factors were specified,w ith a provision of suggestions to forensic pathologists in handling deaths associated w ith ICH,especially sudden unexpected deaths.

Brain-derived neurotrophic factors increase the proliferation and differentiation of endogenous neural stem cells in mouse models of cerebral infarction

BACKGROUND： It has been confirmed that brain-derived neurotrophic factor （BDNF） can promote the proliferation of neural stem cells （NSCs） and protect neuron-like cells in vitro. However, its effect on endogenous NSCs in vivo is still unclear. OBJECTIVE： To evaluate whether BDNF can induce the endogenous NSCs to proliferate and differentiate into the neurons in the mice model of cerebral infarction. DESIGN： A synchronal controlled observation. SETTINGS： Department of Neurology, Microbiology Division of the Department of Laboratory, Tianjin First Central Hospital; Howard Florey Institute, Medical College, the University of Melbourne. MATERIALS： Twenty-four pure breed C57BL/6J mice at the age of 10 weeks old （12 males and 12 females） were divided into saline control group and BDNF-treated group, 6 males and 6 females in each group. METHODS： The experiments were performed at the University of Melbourne from July 2004 to February 2005. ① The left middle cerebral artery （MCA） was ligated in both groups to establish models of cerebral infarction and the Matsushita measuring method was used to monitor the blood flow of the lesioned region supplied by MCA. 75% reduction of blood flow should be reached in the lesioned region. ② At 24 hours after infarction, mice in the BDNF-treated group were administrated with BDNF, which was slowly delivered using an ALZET osmium pump design. BDNF was dissolved in saline at the dosage of 500 mg/kg and injected into the pump, which could release the solution consistently in the following 28 days. The mice in the saline control group accepted the same volume of saline at 24 hours after infarction. ③ The Rotarod function test began at 1 week preoperatively, the time stayed on Rotarod was recorded. The mice were tested once a day till the end of the experiment. At 4 weeks post cerebral infarction, double labeling of Nestin and GFAP, BIH tubulin and CNPase immunostaining was performed to observe the differentiation directions of the re-expressed endogenous NSCs, and the percentages of the cells differentiated into astrocytes, neurons and oligodendrocytes were calculated. MAIN OUTCOME MEASURES： ① The differentiation directions of the re-expressed endogenous NSCs, and the percentage of the cells differentiated into astrocytes, neurons and oligodendrocytes.② Comparison of motor function between the two groups. RESULTS： All the 24 pure C57BL/6J mice were involved in the analysis of results. ①Positively expressed endogenous NSCs appeared in the mice of both groups, and they mainly distributed around the focus of lesion, as well as the contralateral side. The expressed cells in the BDNF-treated group were obviously more than those in the saline control group. ②Activations of endogenous NSCs： At 4 weeks after infarction, re-expressions of endogenous NSCs appeared in both groups. The number of the re-expressed cells in the BDNF-treated group was about 4.2 times higher than that in the saline control group. The percentage of the cells differentiated into neurons in the BDNF-treated group was significantly higher than that in the saline control group （36%, 15%）, the percentage of the cells differentiated into astrocytes was lower than that in the saline control group （54%, 77%）, whereas the percentage of the cells differentiated into oligodendrocytes was similar to that in the saline control group （10%, 8%）. ③ Results of motor functional test： Compared with before cerebral infarction, the mice in both groups manifested as obvious decrease in motor function at 1 week after infarction, whereas the recovery of motor function in the BDNF-treated group was significantly superior to that in the saline control group at 2, 3 and 4 weeks （P 〈 0.01）. CONCLUSION： BDNF can promote the proliferation of endogenous NSCs in the brain of mice with cerebral infarction, it can decrease the differentiation rate of astrocytes, and increase the differentiation rate of neurons. BDNF has small influence on the differentiation of endogenous NSCs into oligodendrocytes, which was not benefit for the recovery of neural axon. Endogenous NSCs may improve the motor function of mice through the above pathways.

WJSC 6^(th) Anniversary Special Issues(2):Mesenchymal stem cells Brain mesenchymal stem cells:The other stem cells of the brain?

Multipotent mesenchymal stromal cells(MSC),have the potential to differentiate into cells of the mesenchymal lineage and have non-progenitor functions including immunomodulation.The demonstration that MSCs are perivascular cells found in almost all adult tissues raises fascinating perspectives on their role in tissue maintenance and repair.However,some controversies about the physiological role of the perivascular MSCs residing outside the bone marrow and on their therapeutic potential in regenerative medicine exist.In brain,perivascular MSCs like pericytes and adventitial cells,could constitute another stem cell population distinct to the neural stem cell pool.The demonstration of the neuronal potential of MSCs requires stringent criteria including morphological changes,the demonstration of neural biomarkers expression,electrophysiological recordings,and the absence of cell fusion.The recent finding that brain cancer stem cells can transdifferentiate into pericytes is another facet of the plasticity of these cells.It suggests that the perversion of the stem cell potential of pericytes might play an even unsuspected role in cancer formation and tumor progression.

Cognitive improvement following transvenous adipose-derived mesenchymal stem cell transplantation in a rat model of traumatic brain injury

The effects of adipose-derived mesenchymal stem cell (ADMSC) transplantation for the repair of traumatic brain injury remain poorly understood. The present study observed neurological functional changes in a rat model of traumatic brain injury following ADMSC transplantation via the tail vein. Cell transplants were observed in injured cerebral cortex, and expression of brain-derived nerve growth factor was significantly increased in the injured hippocampus following transplantation. Results demonstrated that transvenous ADMSC transplants migrated to the injured cerebral cortex and significantly improved cognitive function.

Are human dental papilla-derived stem cell and human brain-derived neural stem cell transplantations suitable for treatment of Parkinson’s disease?

Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson＇s disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups （PBS injection） demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [18F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase （dopaminergic neuronal marker） staining and G protein-activated inward rectifier potassium channel 2 （A9 dopaminergic neuronal marker） were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stern cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.