Immature Neural Tissue Research Articles

High-Density, Conformable Conducting Polymer-Based Implantable Neural Probes for the Developing Brain.

Neurologic and neuropsychiatric disorders substantially impact the pediatric population, but there is a lack of dedicated devices for monitoring the developing brain in animal models, leading to gaps in mechanistic understanding of how brain functions emerge and their disruption in disease states. Due to the small size, fragility, and high water content of immature neural tissue, as well as the absence of a hardened skull to mechanically support rigid devices, conventional neural interface devices are poorly suited to acquire brain signals without inducing damage. Here, the authors design conformable, implantable, conducting polymer-based probes (NeuroShanks) for precise targeting in the developing mouse brain without the need for skull-attached, rigid mechanical support structures. These probes enable the acquisition of high spatiotemporal resolution neurophysiologic activity from superficial and deep brain regions across unanesthetized behavioral states without causing tissue disruption or device failure. Once implanted, probes are mechanically stable and permit precise, stable signal monitoring at the level of the local field potential and individual action potentials. These results support the translational potential of such devices for clinically indicated neurophysiologic recording in pediatric patients. Additionally, the role of organic bioelectronics as an enabling technology to address questions in developmental neuroscience is revealed.

Immature teratoma within an omphalocele: A unique finding

Teratomas are the only true umbilical cord neoplasms. Antenatal diagnosis of an umbilical cord tumor in the presence of an exomphalos is difficult because of the rarity and pleomorphic presentation. We report a case of omphalocele containing an immature umbilical cord teratoma. A 3-day old girl with an antenatally diagnosed omphalocele was found to have, other than intestinal loops and a part of the liver, two solid masses at the caudal aspect near the top of the omphalocele sac. On exploration, a cystic structure with solid components was seen within the sac and excised. Microscopic examination revealed a teratoma with immature neural tissue represented by primitive neural tubes and rosettes. Seen in 4000–5000 live births, 70–80% of omphaloceles are associated with morphologic abnormalities of other systems. Prenatal diagnosis of umbilical cord teratomas is challenging when associated with an exomphalos but should be suspected when a mixed solid and cystic mass is documented attached to the umbilical cord in the midline. Till date, there are 19 reported cases of umbilical teratomas of which only five (26.3%) contained immature tissue. Surgical excision with close follow-up is the recommended treatment. Outcome depends on the presence of associated anomalies, extent of tumor resection, occurrence of surgical complications and the presence of foci of yolk sac tumor in the neoplasm. Immature teratoma within an omphalocele is a rarity. However, the malformation is surgically correctable and prognosis is largely determined by the presence of associated abnormalities.

Laparoscopic Management of a Rare Case of Mature Cystic Teratoma With Immature Neural Tissue and Literature Review

Laparoscopic Management of a Rare Case of Mature Cystic Teratoma With Immature Neural Tissue and Literature Review

Identification of neuron-related genes for cell therapy of neurological disorders by network analysis.

Bone mesenchymal stem cells (BMSCs) differentiated into neurons have been widely proposed for use in cell therapy of many neurological disorders. It is therefore important to understand the molecular mechanisms underlying this differentiation. We screened differentially expressed genes between immature neural tissues and untreated BMSCs to identify the genes responsible for neuronal differentiation from BMSCs. GSE68243 gene microarray data of rat BMSCs and GSE18860 gene microarray data of rat neurons were received from the Gene Expression Omnibus database. Transcriptome Analysis Console software showed that 1248 genes were up-regulated and 1273 were down-regulated in neurons compared with BMSCs. Gene Ontology functional enrichment, protein-protein interaction networks, functional modules, and hub genes were analyzed using DAVID, STRING 10, BiNGO tool, and Network Analyzer software, revealing that nine hub genes, Nrcam, Sema3a, Mapk8, Dlg4, Slit1, Creb1, Ntrk2, Cntn2, and Pax6, may play a pivotal role in neuronal differentiation from BMSCs. Seven genes, Dcx, Nrcam, sema3a, Cntn2, Slit1, Ephb1, and Pax6, were shown to be hub nodes within the neuronal development network, while six genes, Fgf2, Tgfβ1, Vegfa, Serpine1, Il6, and Stat1, appeared to play an important role in suppressing neuronal differentiation. However, additional studies are required to confirm these results.

Gliomatosis Peritonei Arising in Setting of Immature Teratoma of Ovary: A Case Report and Review of Literature.

Gliomatosis peritonei (GP) is an infrequent occurrence, exclusively associated with a mature or immature teratoma of the ovary. GP is defined as miliary implantation of glial tissues on the surface of the visceral or parietal peritoneum with secondary maturation into glial nodules of 1–10 mm. Robboy and Scully have suggested three possible sources of GP: (1) deposition of immature neural tissue with consequent maturation; (2) lymphogenous metastasis; and (3) mature glial cells extruded through a defect in the capsule of the primary tumor [1]. Surgery is the basic treatment for both mature and immature teratomas as well as for peritoneal gliomatosis [2]. In immature teratoma associated with GP, combined chemotherapy is recommended. Surgery and chemotherapy can give longer survival even in recurrent disease [3].

English

BACKGROUND: Immature teratoma is the currently preferred term for the malignant ovarian teratoma composed of a mixture of embryonal and adult tissues derived from all three germ layers, regardless of its gross appearance. AIM: to distinct mature and immature teratoma when dealing with ovarian germ cell tumors. CASE SUMMARY: a 30 year female presented with intra abdominal mass and ascitis. Grossly, variable size nodule and cystic areas are seen. Microscopically, carcinoid like lesion, thyroid tissue immature neural tissue and glandular tissue noted. Diagnosis of immature teratoma grade 3 was made. DISCUSSION: immature teratoma of ovary accounts for 10-20% of all ovarian tumors and is considered second most common germ cell tumor following mature teratoma. It is usually seen in children and adolescents. CONCLUSION: A thorough search for immature elements in a teratoma is necessary for proper grading, management and assessing prognosis of cases with immature

Large Intrathoracic Teratomas in Neonates: Surgical Considerations

We report the case of 3 mediastinal teratomas, 1 intrapericardial immature and 2 mediastinal grade 0, diagnosed in the 38 th week of gestation (intrapericardial immature) in the last stage of pregnancy (mature mediastinal). The surgical resection of the masses was successfully undertaken shortly after birth. The histological description of tumor after excision has reported immature multicystic teratoma Grade 2 of 3, with immature neural tissue and without yolk sac tumor cells (for the intrapericardial case) and mature tissue grade 0 large masses, with all tissues represented at histology (for the extrapericardial case). All neonates showed a favorable postoperative course after excision.

Ovarian sertoli-leydig cell tumour of intermediate-differentiation with heterologous elements comprising of seromucinous epithelial lined cysts and immature neural tissue: an unusual neoplasm

Ovarian Sertoli-Leydig cell tumour (SLCT) is a rare sex cord stromal tumour. Some SLCT, usually of intermediate or poor differentiation show heterologous elements such as gastrointestinal type epithelium, immature cartilage or skeletal muscle. However, SLCT with serous epithelium and immature neural tissue as heterologous elements have not been documented. We describe a rare ovarian SLCT with heterologous elements in a 25-year-old woman with post-partum abdominal swelling and pain. Heterologous elements included cystic locules lined by a benign epithelium of serous and mucinous cells and a small foci of immature neural tissue. SCLT withheterologousmucinous elementsshouldbedistinguished from pure mucinous cystic ovarian tumours which may appear similar macroscopically and present with virilising symptoms. Heterologous elements may present in a variable proportion from microscopic foci to predominant tumour masking the SLCT. This case highlights the importance of extensive sampling because of common and overlapping morphological features with other ovarian tumours.

Imprint cytology of high‐grade immature ovarian teratoma: A case report, literature review, and distinction from other ovarian small round cell tumors

Immature ovarian teratoma (IOT) is a rare and aggressive malignant neoplasm characterized by immature neural tissue. The cytomorphologic features have only rarely been described. We herein describe an additional case and review the literature regarding this entity. To the best of our knowledge, this is the first reported case with imprint cytology. A 35-year-old woman presented with a pelvic mass which was resected and sent for frozen section evaluation. Imprint smears and frozen section of the mass were diagnostic of IOT. IOT has diagnostic cytologic features which show complete concordance with histology. Differential diagnoses include other small round cell neoplasms such as ovarian neuroblastoma, small cell carcinoma of hypercalcemic type, primitive neuroectodermal tumor, Wilm's tumor, desmoplastic small round cell tumor, and Non-Hodgkin lymphoma. Distinguishing IOT from these tumors can be challenging however if diligent morphologic study and/or ancillary studies are performed accurate diagnosis is possible.

A large teratoma of the hard palate: a case report

Congenital teratoma is a rare malformation, and few papers have been published about it. We present a large teratoma that arose from the hard palate in a neonate. The obstructive mass caused maternal polyhydramnios and was identified prenatally by ultrasonography. The mother went into labour at 35 week's gestation at home. The child was in respiratory distress as a result of airway obstruction, and a tracheostomy was done when she was 4 hours old. She also had major cardiac abnormalities. The palatal mass was removed successfully at 4 weeks of age. The typical components of a teratoma were identified including immature neural glial tissue.

Neurogenic potential of human mesenchymal stem cells revisited: analysis by immunostaining, time-lapse video and microarray

The possibility of generating neural cells from human bone-marrow-derived mesenchymal stem cells (hMSCs) by simple in vitro treatments is appealing both conceptually and practically. However, whether phenotypic modulations observed after chemical manipulation of such stem cells truly represent a genuine trans-lineage differentiation remains to be established. We have re-evaluated the effects of a frequently reported biochemical approach, based on treatment with butylated hydroxyanisole and dimethylsulphoxide, to bring about such phenotypic conversion by monitoring the morphological changes induced by the treatment in real time, by analysing the expression of phenotype-specific protein markers and by assessing the modulation of transcriptome. Video time-lapse microscopy showed that conversion of mesenchymal stem cells to a neuron-like morphology could be reproduced in normal primary fibroblasts as well as mimicked by addition of drugs eliciting cytoskeletal collapse and disruption of focal adhesion contacts. Analysis of markers revealed that mesenchymal stem cells constitutively expressed multi-lineage traits, including several pertaining to the neural one. However, the applied ;neural induction' protocol neither significantly modulated the expression of such markers, nor induced de novo translation of other neural-specific proteins. Similarly, global expression profiling of over 21,000 genes demonstrated that gene transcription was poorly affected. Most strikingly, we found that the set of genes whose expression was altered by the inductive treatment did not match those sets of genes differentially expressed when comparing untreated mesenchymal stem cells and immature neural tissues. Conversely, by comparing these gene expression profiles with that obtained from comparisons between the same cells and an unrelated non-neural organ, such as liver, we found that the adopted neural induction protocol was no more effective in redirecting human mesenchymal stem cells toward a neural phenotype than toward an endodermal hepatic pathway.

Immature ovarian teratoma in an adolescent: a case report and review of the literature

BackgroundBenign cystic teratomas are relatively common tumors in reproductive age women, but can occur at any age. While the incidence of malignant elements in a teratoma is low (approximately 1–2%), the survival of patients with immature teratoma is poor. Definitive diagnosis is mandatory. CaseWe describe a case of a 13-year-old African American female, gravida 0, presenting with a large pelvic mass, determined to be a benign cystic teratoma by intra-operative frozen section. However, due to the size of the tumor and the preponderance of neural elements we performed a full surgical staging procedure (excluding hysterectomy and complete removal of adnexa). The final pathology report revealed foci of immature neural tissue, with a final diagnosis of an immature cystic teratoma Stage Ia. ConclusionFoci of immature neural elements can be readily missed on frozen section, especially with a large tumor. Full surgical staging at the time of initial laparotomy is justified when encountering an apparently mature cystic teratoma with a preponderance of neural elements on frozen section.

Recurrent immature teratoma: Lack of correlation between serum level and immunohistochemical detection of serum alpha-fetoprotein

We present the clinicopathologic and immunohistochemical features of a pure immature ovarian teratoma that had arisen in a 15-year-old girl. At original diagnosis immature extra ovarian implants were noted (grade 3) accompanied by moderately elevated serum alpha-fetoprotein (AFP) levels. AFP was immunohistochemically demonstrable in immature endodermal elements. The immature neural tissue present was negative for AFP, and no other tumor elements were recognisable. Serum AFP fell post-operatively to within normal limits. Despite five courses of chemotherapy and asymptomatic status, the patient re-presented 15 months after original diagnosis with a massive abdominal and pelvic tumor recurrence with predominantly mature glial tissue, but some persistent immature foci. There was no associated increase in serum AFP at this time. AFP was, however, persistently detectable immunohistochemically in immature endodermal components only. Immature neural elements were no longer identified. Disappearance of immature neural tissue in the tumor recurrence may have been related to chemotherapy. This case demonstrates the lack of correlative ability of serum AFP levels with both clinical behaviour and immunohistochemical demonstration of AFP expression in the tumor recurrence.

A teratocarcinoma-derived neurotrophic activity.

In a search for nerve growth factor (NGF) in tissue extracts of a murine transplantable teratocarcinoma that harbours immature neural tissue in abundance, a trypsin-sensitive and heat labile neurotrophic activity was identified. The final protein fraction obtained by cation exchange chromatography contained five proteins with mol. wts ranging from 52 to 72 kD. It supported the growth and differentiation of immature neurones in neonatal rat cerebellar cultures but had no effect on embryonic chick dorsal root ganglia which are the classical targets for NGF.

Immature neural tissue grafts in Parkinson's disease

Intracerebral transplantation of immature neural tissue is a promising therapeutical approach that has the potential of restoring damaged neuronal circuitries and reversing functional deficits. The development of the technique as a human application has progressed the furthest in Parkinson's disease (PD), with the demonstration of significant longlasting functional improvements, in combination with evidence of surviving grafted tissue, using a fluorodopa positron emission tomography (PET) scanning technique in a few patients. Although the technique is promising, and the effects observed are significant and of clinical importance for the grafted patients in the best cases so far, there are still incomplete effects and no transplantation treatment is suggested since there are still several technical aspects that might further improve the outcome. The progress of the development in the field is briefly reviewed.

N-myc gene amplification and neuron specific enolase production in immature teratomas

The primary tumour tissues from 13 teratomas were investigated, 3 cases of immature teratoma (1 of pure type and 2 of mixed type), 5 cases of dermoid cyst, and 5 cases of mature solid teratoma, with special reference to N-myc gene amplification, productivity of neuron specific enolase (NSE), and the presence of double minutes (DMs). The possible relationship between these variables and malignancy of the tumours was also examined. N-myc gene amplification and NSE production were recognized in the primary tumour tissues and the first and the third passage cultured cells of all of the 3 cases of immature teratoma containing immature neural tissues. In 2 cases DMs were recognized. In dermoid cysts and mature teratoma, neither N-myc gene amplification nor NSE production were recognized in either the primary tumour tissues or cultured cells. The chromosomes were normal. Malignancy of teratoma is generally decided by the clinical stage and histological grade, but a more securely based decision is necessary where an immature teratoma contains immature neural tissues. The presence of N-myc gene amplification, NSE productivity and the presence of DMs may be valuable.

Delayed grafting of fetal CNS tissue into chronic compression lesions of the adult cat spinal cord

This review summarizes a series of experiments involving transplants of embryonic feline CNS tissue into chronic compression lesions of the adult cat spinal cord. Fetal spinal cord (FSC), caudal brainstem (BSt), neocortex (NCx) or a combination of either FSC/NCx or FSC/BSt was transplanted as solid pieces or as a suspension of dissociated cells into the developed cystic cavities produced by static-load compression trauma 2-10 weeks prior to grafting. All cats were immunosuppressed with cyclosporin A and their locomotor function was assessed for 6-30 weeks. Following the period of evaluation, all recipients were perfused with fixative and tissue specimens, taken at the transplantation site, were processed for general histological and/or immunocytochemical analysis. Viable graft tissue was found in all animals with the exception of two cats which showed active rejection of their transplants. All of the viable intraspinal grafts were extensively vascularized and did not show any signs of imminent or on-going tissue rejection. Fetal cat CNS grafts showed an extended maturational phase in that features of immature neural tissue (e.g. a paucity of myelination) were still seen even 6-9 weeks after transplantation. By 20-30 weeks, FSC and BSt grafts had attained a more advanced stage of maturation. Transplants in these chronic lesions were extensively blended with both the gray and white matter of the host spinal cord and could be visualized by magnetic resonance imaging (MRI). MRI could also detect regions of cavitation at the graft-host interface, as well as within some transplants. While preliminary evidence from behavioral studies suggest that the FSC and BSt grafts may improve or spare locomotor function in some recipients, a more rigorous analysis of post-grafting locomotor function is required to determine conclusively the functionality of these transplants.

Microglial and neural differentiation in human teratomas.

Ten human teratomas arising outside the central nervous system (CNS) were studied using a panel of immunohistochemical, and lectin histochemical stains to determine the relationship of the presence of microglia to markers of neural maturity or differentiation. Microglia, identified by silver carbonate, Ricinus communis agglutinin-1 (RCA-1), or both were found in eight out of ten cases. They were common in mature areas which also had S-100, glial fibrillary acidic protein, vimentin, neurofilament, and synaptophysin immunostaining. Microglia were distinguished from macrophages in necrotic foci. Cells which were RCA-1 positive and silver carbonate positive were found in immature neural tissues but these lacked all typical features of microglia. These observations indicate that true microglia are frequent in nonCNS teratomas and that they are found in association with other indicators of neural maturation. The presence of possible precursors in immature areas suggests that microglia undergo maturation concurrent with neural differentiation in these tumors.

Immature neural elements in immature teratomas. An immunohistochemical and ultrastructural study.

Immature neural tissue pathobiology in teratomas may have important implications for clinical prognosis, nervous system embryology, and neurological oncology. However, immunohistochemical and ultrastructural examinations of these neoplasms have been scarce. The authors examined immunohistochemically the immature neural elements in nine immature teratomas. Using modified peroxidase-antiperoxidase (PAP) immunoperoxidase (IP) techniques, they evaluated the immunoreactivity to glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), neurofilament (NF), chromogranin (CG), and vimentin (VM). All nine teratomas were immunoreactive for both GFAP and NSE, one was reactive for NF, and five (56%) were immunoreactive for vimentin. All cases were nonreactive for chromogranin. In addition, ultrastructural examination (electron microscopic [EM]) was performed on eight of these tumors. By EM examination, both astrocytes and oligodendroglia were identified in varying stages of development. Astrocytes often displayed abundant intermediate filaments. However, primitive undifferentiated cells were also found. Neuronal differentiation included long cell processes with tubules and filaments, vesicles, rare dense-core granules, and synapses. Ependymal differentiation (cilia, microvilli, prominent junctions) was observed in two cases. Pigmented retinal epithelium was seen in one tumor. No ambiguous (hybrid) cells were identified. Cellular interactions usually resembled the relationships found in normal adult brain tissue.

Cryopreservation of fetal rat brain tissue later used for intracerebral transplantation

Intracerebral grafting of immature brain tissue is now widely used as a tool to study neuronal development and regeneration in the brain and spinal cord. This has stimulated the interest in methods for storage of such tissue before transplantation. In this study a method for cryopreservation of immature rat central nervous tissue is presented and discussed in relation to current cryobiological principles. The method was applied to brain tissue from 16- and 17-day-old fetal rats, including the neocortex, habenula, septum and basal forebrain, cerebellum, and retina. After storage in liquid nitrogen from 6 to 52 days the tissue was grafted into the brain of adult rats. The recipients survived for 23 to 673 days before their brains were processed by current neuroanatomical, histological methods. The presence of graft tissues was recorded and their cellular and connective organization was examined, including their exchange of nerve connections with the host brain. The results obtained were comparable with results from other studies where the same tissues were grafted immediately after removal from the donor, and a study of cryopreservation of developing hippocampal tissue. We conclude that cryopreservation is a reliable method for storage of immature neural tissue later to be used for intracerebral grafting.