Expression of Nogo-A in dorsal root ganglion in rats with cauda equina injury.

OBJECTIVE: To investigate the expression of Nogo-A in dorsal root ganglion (DRG) in rats with cauda equina injury and the therapeutic effects of blocking Nogo-A and its receptor. METHODS AND MATERIALS: Fifty-eight male Sprague-Dawley rats were divided randomly into either the sham operation group (n = 24) or the cauda equina compression (CEC) control group (n = 34). Behavioral, histological, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analyses were conducted to assess the establishment of the model. The dynamic expression change of Nogo-A was evaluated using real time-qPCR. Immunofluorescence was used to evaluate the expression of Nogo-A in the DRG and cauda equina. Furthermore, 20 male Sprague-Dawley rats were equally divided into 4 groups, including the sham group, the CEC group, the NEP1-40 (the NgR antagonist peptide) treatment group, and the JTE-013 (the S1PR2 antagonist) treatment group. Behavioral assessments and western blotting were used to evaluate the therapeutic effect of cauda equina injury via blocking Nogo-A and its receptor. RESULTS: Tactile allodynia and heat hyperalgesia in the CEC model developed as soon as 1 day after surgery and recovered to normal at 7 days, which was followed by the downregulation of Nogo-A in DRG neurons. However, the locomotor function impairment in the CEC model showed a different prognosis from the sensory function, which was consistent with the expression change of Nogo-A in the spinal cord. Immunofluorescence results also demonstrated that Nogo A-positive/NF200-negative neurons and axons increased in the DRG and cauda equina 7 days after surgery. Surprisingly, Schwann cells, which myelinate axons in the PNS, also expressed considerable amounts of Nogo-A. Then, after blocking the Nogo-A/NgR signaling pathway by NEP1-40, significant improvement of mechanical allodynia was identified in the first 2 days after the surgery. Western blotting suggested the NEP1-40 treatment group had lower expression of cleaved caspase-3 than the CEC and JTE-013 treatment group. CONCLUSION: Neuronal Nogo-A in the DRG may be involved in regeneration and play a protective role in the CEC model. Whereas Nogo-A, released from the injured axons or expressed by Schwann cells, may act as an inhibiting factor in the process of CEC repairment. Thus, blocking the Nogo-A/NgR signaling pathway can alleviate mechanical allodynia by apoptosis inhibition.

The immunohistochemical, DNA methylation, and chromosomal copy number profile of cauda equina paraganglioma is distinct from extra-spinal paraganglioma.

Paragangliomas are neuroendocrine tumors of the autonomic nervous system that are variably clinically functional and have a potential for metastasis. Up to 40% occur in the setting of a hereditary syndrome, most commonly due to germline mutations in succinate dehydrogenase (SDHx) genes. Immunohistochemically, paragangliomas are characteristically GATA3-positive and cytokeratin-negative, with loss of SDHB expression in most hereditary cases. In contrast, the rare paragangliomas arising in the cauda equina (CEP) or filum terminale region have been shown to be hormonally silent, clinically indolent, and have variable keratin expression, suggesting these tumors may represent a separate pathologic entity. We retrospectively evaluated 17 CEPs from 11 male and 6 female patients with a median age of 38 years (range 21-82), none with a family history of neuroendocrine neoplasia. Six of the 17 tumors demonstrated prominent gangliocytic or ganglioneuromatous differentiation. By immunohistochemistry, none of the CEPs showed GATA3 positivity or loss of SDHB staining; all 17 CEPs were cytokeratin positive. Genome-wide DNA methylation profiling was performed on 12 of the tumors and compared with publicly available genome-wide DNA methylation data. Clustering analysis showed that CEPs form a distinct epigenetic group, separate from paragangliomas of extraspinal sites, pheochromocytomas, and other neuroendocrine neoplasms. Copy number analysis revealed diploid genomes in the vast majority of CEPs, whereas extraspinal paragangliomas were mostly aneuploid with recurrent trisomy 1q and monosomies of 1p, 3, and 11, none of which were present in the cohort of CEP. Together, these findings indicate that CEPs likely represent a distinct entity. Future genomic studies are needed to further elucidate the molecular pathogenesis of these tumors.

Differential Neuroproteomic and Systems Biology Analysis of Spinal Cord Injury.

Acute spinal cord injury (SCI) is a devastating condition with many consequences and no known effective treatment. Although it is quite easy to diagnose traumatic SCI, the assessment of injury severity and projection of disease progression or recovery are often challenging, as no consensus biomarkers have been clearly identified. Here rats were subjected to experimental moderate or severe thoracic SCI. At 24h and 7d postinjury, spinal cord segment caudal to injury center versus sham samples was harvested and subjected to differential proteomic analysis. Cationic/anionic-exchange chromatography, followed by 1D polyacrylamide gel electrophoresis, was used to reduce protein complexity. A reverse phase liquid chromatography-tandem mass spectrometry proteomic platform was then utilized to identify proteome changes associated with SCI. Twenty-two and 22 proteins were up-regulated at 24 h and 7 day after SCI, respectively; whereas 19 and 16 proteins are down-regulated at 24 h and 7 day after SCI, respectively, when compared with sham control. A subset of 12 proteins were identified as candidate SCI biomarkers - TF (Transferrin), FASN (Fatty acid synthase), NME1 (Nucleoside diphosphate kinase 1), STMN1 (Stathmin 1), EEF2 (Eukaryotic translation elongation factor 2), CTSD (Cathepsin D), ANXA1 (Annexin A1), ANXA2 (Annexin A2), PGM1 (Phosphoglucomutase 1), PEA15 (Phosphoprotein enriched in astrocytes 15), GOT2 (Glutamic-oxaloacetic transaminase 2), and TPI-1 (Triosephosphate isomerase 1), data are available via ProteomeXchange with identifier PXD003473. In addition, Transferrin, Cathepsin D, and TPI-1 and PEA15 were further verified in rat spinal cord tissue and/or CSF samples after SCI and in human CSF samples from moderate/severe SCI patients. Lastly, a systems biology approach was utilized to determine the critical biochemical pathways and interactome in the pathogenesis of SCI. Thus, SCI candidate biomarkers identified can be used to correlate with disease progression or to identify potential SCI therapeutic targets.

Mitigated Tregs and augmented Th17 cells and cytokines are associated with severity of experimental autoimmune neuritis.

Experimental autoimmune neuritis (EAN), an animal model of human Guillain-Barré syndrome, has long been considered as a T helper (Th) 1 cell-mediated autoimmune disorder. However, deficiency of IFN-γ, a signature Th1 cytokine, aggravated EAN, with features of elevated production of IL-17A, despite an alleviated systemic Th1 immune response. We hypothesized that Th17 cells and their cytokines might play a pathogenic role in EAN. To further clarify the roles of these Th and regulatory T cell (Treg) cytokines in the pathogenesis of EAN and their interrelationship, we investigated the expression of Th1/Th2/Th17/Treg cytokines in EAN in this study. We found that the levels of Th17 cells and IL-17A in cauda equina (CE)-infiltrating cells and splenic mononuclear cells (MNCs) as well as in serum paralleled the disease evolution, which increased progressively during the initiation stage and reached higher value at the peak of EAN. The same pattern was also noticed for the expression of IL-22. The diverse expression profiles of FoxP3, IL-17 receptors A and C were seen in CE-infiltrating cells and splenic MNCs in EAN. These findings indicate a major pro-inflammatory role of Th17 cells and IL-17A in the pathogenesis of EAN. Therapeutic interventions may be focused upon inhibiting Th17 cells and their cytokines in the early phase of EAN, so as to delay and suppress clinical signs of the disease, which has relevance for future studies on pathogenesis and treatment of GBS in humans.

Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21.

We previously localized and fine-mapped Charcot Marie Tooth 4A (CMT4A), the autosomal recessive, demyelinating peripheral neuropathy, to chromosome 8. Through additional positional cloning, we have identified a good candidate gene, encoding ganglioside-induced differentiation-associated protein-1 (GDAP1). We found three different mutations in four different Tunisian families-two nonsense and one missense mutation. How mutations in GDAP1 lead to CMT4A remains to be understood.

Cauda Equina Neuroendocrine Tumors: Distinct Epithelial Neuroendocrine Neoplasms of Spinal Origin.

The tumor formerly known as "cauda equina paraganglioma" was recently renamed as cauda equina neuroendocrine tumor (CENET) based on distinct biological and genetic properties. Nevertheless, it remains insufficiently understood. For this study, we retrieved CENETs (some previously reported), from the pathology files of 3 institutions; we examined their immunohistochemical profile, including common neuroendocrine tumor-associated hormones and transcription factors. We identified 24 CENETs from 7 female and 17 male adult patients, with a median age of 47 years. Six included neurofilament-positive ganglion cells. All tumors tested were positive for INSM1, synaptophysin, chromogranin A, SSTR2, and CD56 as well as at least 1 keratin (AE1/AE3, CAM5.2); CK7 and CK20 were negative. Glial fibrillary acidic protein was negative, except for peripheral nontumoral elements. S100 protein was variable but mainly expressed in scattered sustentacular cells. All but 1 tumor tested were positive for HOXB13; several stained for SATB2, and all tumors were consistently negative for GATA3. All tumors tested were negative for transcription factors found in various other epithelial neuroendocrine neoplasms including TTF1, CDX2, PIT1, TPIT, SF1, and PAX8; staining for T-brachyury was negative. Four of 5 CENETs tested had at least focal tyrosine hydroxylase reactivity. Serotonin expression was detected in all 21 tumors tested; it was diffusely positive in 5 and had variable positivity in the remainder. A few tumors had scattered cells expressing gastrin, calcitonin, pancreatic polypeptide, and peptide YY, while glucagon, adrenocorticotropic hormone, and monoclonal carcinoembryonic antigen were negative. PSAP expression was found focally in 4 of 5 tumors examined. SDHB was consistently intact; ATRX was intact in 14 tumors and showed only focal loss in 3. The median Ki-67 labeling index was 4.5% (range: 1% to 15%). We conclude that CENET represents a distinct neuroendocrine neoplasm; the subset with ganglion cells qualifies for designation as composite gangliocytoma/neuroma-neuroendocrine tumor (CoGNET) as defined in the 2022 WHO classification of neuroendocrine neoplasms. In addition to INSM1, chromogranin, synaptophysin, and keratins, the most characteristic finding is nuclear HOXB13 expression; a subset also express SATB2. Serotonin is the most common hormone expressed. The cytogenesis and pathogenesis of these lesions remains unclear.

Cauda equina neuroendocrine tumors show biological features distinct from other paragangliomas and visceral neuroendocrine tumors.

Cauda equina neuroendocrine tumors (CENETs) are neoplasms of uncertain histogenesis with overlapping features between those of paragangliomas (PGs) and visceral neuroendocrine tumors (NETs). We have explored their biological relationship to both subsets of neuroendocrine neoplasms. The clinical and radiological features of a cohort of 23 CENETs were analyzed. A total of 21 cases were included in tissue microarrays, along with a control group of 38 PGs and 83 NETs. An extensive panel of antibodies was used to assess epithelial phenotype (cytokeratins, E-cadherin, EpCAM, Claudin-4, EMA, CD138), neuronal and neuroendocrine features (synaptophysin, chromogranin A, INSM1, neurofilaments, NeuN, internexin-α, calretinin), chromaffin differentiation (GATA3, Phox2b, tyrosine hydroxylase), and possible histogenesis (Sox2, T-brachyury, Oct3/4, Sox10). The cohort included 5 women (22%) and 18 men (78%). The average age at the time of surgery was 48.3 years (range from 21 to 80 years). The average diameter of the tumors was 39.27 mm, and invasion of surrounding structures was observed in 6/21 (29%) tumors. Follow-up was available in 16 patients (median 46.5 months). One tumor recurred after 19 months. No metastatic behavior and no endocrine activity were observed. Compared to control groups, CENETs lacked expression of epithelial adhesion molecules (EpCAM, CD138, E-cadherin, Claudin-4), and at the same time, they lacked features of chromaffin differentiation (GATA3, Phox2b, tyrosine hydroxylase). We observed no loss of SDHB. Cytokeratin expression was present in all CENETs. All the CENETs showed variable cytoplasmic expression of T-brachyury and limited nuclear expression of Sox2. These findings support the unique nature of the neoplasm with respect to NETs and PGs.

[Multiple gliosarcoma metastases in the cauda equina roots].

The authors report a rare a case of gliosarcoma metastases in a 28-year-old male patient. The cauda equina roots were involved after brain tumor 16 months ago, which, on microscopic study, had a biphasic pattern and heterogeneous staining in the reaction with antibody to GFAP and vimentin; the tumor cells did not express EMA, EA, and desmin. Gliosarcoma was diagnosed, by taking into account morphological and immunohistochemical data. Tumor tissue of the cauda equine roots had the same immunophenotype as the brain tumor with a predominance of glial component, which permitted the source of metastases to be ascertained.

Spatiotemporal expression of neurogenic locus notch homolog protein 1 in developing caudal spinal cord of fetuses with anorectal malformations from ETU-fed rats.

Complications, such as fecal soiling, incontinence, and constipation, are major health issues for patients with anorectal malformations (ARMs) after surgery. Dysplasia of the caudal spinal cord is an increasingly pivotal area in the field of postoperative complications for patients with ARMs. However, the existing research has not fully defined the mechanism underlying ARMs development. The neurogenic locus notch homolog (Notch) signaling pathway comprises several highly conserved proteins that are involved in spinal cord developmental processes. In the present study, the emerging role of Notch1 in fetal lumbosacral spinal cords was investigated in a rat model of ARMs using ethylene thiourea. Immunohistochemical staining, western blot and quantitative reverse transcription real-time polymerase chain reaction were utilized to analyze spatiotemporal expression of Notch1 on embryonic days (E) 16, E17, E19, and E21. The expression levels of the neuronal marker neurofilament and recombination signal-binding protein-J protein were evaluated for temporal correlations to Notch1 expression. The results implied that Notch1 expression was reduced in lumbosacral spinal cord neurons of ARMs embryos compared to control embryos. These results showed that, in ARMs embryos decreased Notch1 expression is related to the dysplasia of the caudal spinal cord during embryogenesis, indicating that Notch signaling may participate pathogenic embryonic lumbosacral spinal development and may be associated with postoperative complications of ARMs.

Dorsal cauda equina nerve root enhancement on magnetic resonance imaging due to ANNA-1-associated paraneoplastic polyneuropathy.

A 69-year-old female presented with subacute onset ascending weakness and paraesthesias. She was initially diagnosed with Guillain-Barré syndrome (GBS) based on her clinical presentation and cerebrospinal fluid (CSF) analysis showing albuminocytological dissociation. However, she was later found to have anti-neuronal nuclear antibody 1 (ANNA-1/anti-Hu)-positive CSF and was subsequently diagnosed with small-cell lung cancer. Her neurological symptoms were ultimately attributed to ANNA-1/anti-Hu-associated paraneoplastic polyneuropathy. During the course of her evaluation, she had magnetic resonance imaging findings of dorsal predominant cauda equina nerve root enhancement, which has not been previously described. The only previously reported case of cauda equina enhancement due to ANNA-1-associated polyneuropathy described ventral predominant findings. The distinction between ventral and dorsal enhancement is important, since it suggests that different patterns of nerve root involvement may be associated with this paraneoplastic syndrome. Therefore, ANNA-1-associated paraneoplastic inflammatory polyneuropathy can be considered in the differential diagnosis of cauda equina nerve root enhancement with ventral and/or dorsal predominance. This can potentially be helpful in differentiating ANNA-1 polyneuropathy from GBS, which classically has ventral predominant enhancement.

Paraganglioma of the filum terminale: case report.

BACKGROUND: Paragangliomas affecting the filum terminale are extremely rare, benign tumors. The literature yielded thirty-two cases of paraganglioma in this site. CASE PRESENTATION: A 49 year-old-man, whose presenting symptoms were low back pain and left leg weakness, was diagnosed as having a paraganglioma of the filum terminale. The clinical, histological and radiological characteristics of this case, that brings the total number of cases described to 33, are discussed in the light of published data. CONCLUSIONS: This extremely rare pathology can usually be successfully treated by total surgical resection, which represents the gold standard. In the event of incomplete removal, assiduous long-term follow-up is mandatory.

Metabolic Changes in Serum in the Rat Model of Cauda Equina Injury.

OBJECTIVE: To identify the potent metabolic biomarkers of cauda equina injury (CEI). METHODS: A total of 50 Sprague-Dawley rats were used to establish the CEI model in this study. The serum was collected at 12 hours, 1 day, 2 days, and 7 days after surgery. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was performed to analyze metabolic changes in the serum of the CEI rats from different groups. The differences between the metabolic profiles of the rats in 5 groups were analyzed using partial least squares discriminant analysis (PLS-DA). RESULTS: Metabolic profiling revealed significant differences between the sham operated and other groups. A total of 57 potential CEI metabolite biomarkers were identified between the sham operated group and the model groups at the different time points. Principal component analysis and PLS-DA analyses revealed clear segregation between CEI versus sham operation group. These potential biomarkers appear in 15 metabolic pathways. CONCLUSIONS: Using metabolomic analysis, we were able to identify the novel serum biomarkers of CEI that may be relevant to the diagnosis and prognosis of CEI. In addition, our pathway analysis provides important insights into the etiology of CEI and a basis for clinical diagnosis, locating biomarkers in the early stages of the pathological process.

Structures of filum terminale and characteristics of ependymal cells of its central canal in rats.

The filum terminale (FT) is a potential source of ependymal cells for transplantation. The present study was performed to clarify the characteristics of ependymal cells of the central canal (CC) of the FT in rats. The FT was a thin strand continuous with the conus medullaris (CM), a caudal end of the main spinal cord, situated at the L3-4 level in adult rats. The border between the CM and FT was not visible, but could be defined as the site where the strand was as thin as its more caudal segment. While the CM contained an appreciable amount of white and grey matter associated with the CC at its center, the FT had no or only a negligible amount of such spinal cord parenchymal tissue. The FT was tracked ca. 4 cm from the site defined above to the level of S4-5 in adult rats. The rostral part of the FT (FTI) included within the cauda equina is exposed to cerebrospinal fluid, whereas the more caudal part (FTE) was surrounded by a dense layer of connective tissue. Almost all ependymal cells were immunostained for Sox2, Sox9, FoxJ1, and CD133, generally recognized immunochemical markers for ependymal cells of the CC in the spinal cord. Ependymal cells of the CC of FT exhibited almost the same structural and immunohistochemical characteristics as those of the CC of the main spinal cord. Ependymal cells of FTI covered by a thin layer of connective tissue are considered appropriate for transplantation.

Neurochemical architecture of the filum terminale in the rat.

Contrary to the widespread assumption, the filum terminale in the rat possesses a precise glial and neuronal organization. The processes of glial fibrillary acidic protein-stained astrocytes form a rich, three dimensional array. The crescent shaped white matter could be outlined with antibody detecting oligodendrocytes. The neurons in the filum terminale, labeled with neuron-specific nuclear protein, are distributed in a small midline group (dorsal nucleus) dorsal to and in two symmetrical clusters at both sides of the central canal (lateral nuclei). Nitric oxide synthase-, calretinin-, choline acetyltransferase-, substance P- and neurokinin receptor-1-immunoreactive neurons were detected in the lateral nuclei. Axons were classified based on their course and termination. Small number of calcitonin gene-related peptide-immunoreactive fibers was found exclusively in the dorsal nucleus. Nitric oxide synthase-, substance P-, and neurokinin receptor-1-stained axon arborizations were detected mainly in the lateral nucleus. A dense array of extremely fine vesicular glutamate transporter 2- and fine, synaptophysin-immunoreactive varicosities covered densely the lateral nuclei. Fine glycine-transporter 2-immunoreactive axon arborization like structures were seen also in the lateral nucleus. Vesicular glutamate transporter 1- and choline acetyltransferase-immunoreactive axons arborized in the entire gray matter. Serotonin- and enkephalin-immunoreactive fibers congregated in the dorsolateral portion of the white matter, called "shoulder region", while calretinin- and thick, varicose neurokinin receptor-1-stained axons were also seen in the same area of the white matter. Synaptophysin-immunoreactive fine varicosities colocalized only with vesicular glutamate transporter 2 immunoreaction. Substance P and glycine-transporter 2-immunoreactive puncta were found in close contact with neurokinin receptor-1-immunostained perikarya and dendrites.

The transthyretin gene is expressed in human and rodent dorsal root ganglia.

The transthyretin (TTR) gene is mainly expressed in the liver and choroid plexus of the brain. Most cases of familial amyloidotic polyneuropathy (FAP) are caused by TTR gene mutations, and characterized by amyloid deposition in the peripheral nervous system. We hypothesized that the TTR gene may be expressed in the peripheral nervous system. We analyzed TTR gene expression in several parts of the human, mouse and rat peripheral nervous systems using RT-PCR. To determine the sites of TTR synthesis in the dorsal root ganglia (DRG), mouse DRG were examined by in situ hybridization, laser capture microdissection and RT-PCR, and immunohistochemistry. TTR mRNA was detected in the DRG and cauda equina of humans and rodents by RT-PCR. TTR mRNA was not detected in the sural nerve, lumbar plexus or sympathetic ganglia in humans, or in the sciatic nerve in rodents. In mouse DRG, TTR mRNA was localized in the peripheral glial cells. No TTR-like immunoreactivity was observed in these tissues except for the perineurium. The TTR gene is probably expressed in the peripheral glial cells of the DRG. TTR synthesis in the DRG may be important for the involvement of the peripheral nervous system in FAP.

Characterization of the Filum terminale as a neural progenitor cell niche in both rats and humans.

Neural stem cells (NSCs) reside in a unique microenvironment within the central nervous system (CNS) called the NSC niche. Although they are relatively rare, niches have been previously characterized in both the brain and spinal cord of adult animals. Recently, another potential NSC niche has been identified in the filum terminale (FT), which is a thin band of tissue at the caudal end of the spinal cord. While previous studies have demonstrated that NSCs can be isolated from the FT, the in vivo architecture of this tissue and its relation to other NSC niches in the CNS has not yet been established. In this article we report a histological analysis of the FT NSC niche in postnatal rats and humans. Immunohistochemical characterization reveals that the FT is mitotically active and its cells express similar markers to those in other CNS niches. In addition, the organization of the FT most closely resembles that of the adult spinal cord niche. J. Comp. Neurol. 525:661-675, 2017. © 2016 Wiley Periodicals, Inc.

Neuroprotective effect of hydrogen sulfide on acute cauda equina injury in rats.

BACKGROUND: Hydrogen sulfide (H2S), as a novel gaseous messenger molecule, plays an important role in signal transduction and biological modulation. PURPOSE: In the present study the effect of H2S after compression injury of cauda equina was studied. STUDY DESIGN: The setting of this study is the laboratory investigation. METHODS: A total of 162 rats were randomly allocated into three groups: sham group, compression group, and H2S group. Cauda equina compression (CEC) injury in rats was induced by implanting silicone gels (10×1×1 mm) into the epidural spaces L5 and L6; laminectomy was performed at the L4 level of the vertebra in the sham-operated group. The experimental group was treated with sodium hydrosulfide intraperitoneally (20 µmol/kg body weight), whereas the compression and sham groups received equal volumes of physiological saline. Levels of malonaldehyde (MDA) and glutathione (GSH) were determined immediately before CEC surgery, 12 h, 24 h, 48 h, and 72 h after CEC surgery. Furthermore, hematoxylin and eosin (H&E) staining and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end labeling (TUNEL) assay were performed 48 h after CEC. RESULTS: Hematoxylin and eosin staining showed that myelin sheath and the cauda equina fibers in the compression group were less compact and highly degenerated compared with the sham group, and that H2S treatment could improve the status. Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end labeling staining exhibited that decreased number of TUNEL positive cells was found in the H2S group than in the compression group. The level of MDA was increased in the sham and H2S groups compared with the compression group (p<.05, p<.01), whereas the level of GSH was decreased (p<.05, p<.01). CONCLUSIONS: With the above data, we conclude that H2S could reduce the oxidative stress and has neuroprotective effect in acute cauda equina syndrome.

November 2004: intradural mass of the cauda equina in a woman in her early 60s.

November 2004. A 63-year-old woman presented with slowly aggravating lower back pain and recent urinary urge incontinence. MRI revealed a sharply-delineated, partly cystic intradural mass with inhomogenous contrast-enhancement and ectatic vessels at the upper pole. An ependymoma was suspected, and the tumor was resected in toto. Histologically, at first glance, the tumor strongly resembled an ependymoma, showing a monomorphic cellular pattern, perivascular pseudorosettes and ependymal canal-like structures. However, the finding of a delicate collagen capsule, compartmentation of tumor cells into zellballen and the presence of ganglionic cells were untypical. These features were indicative of a paraganglioma with a gangliocytic component. Immunoreactivity of the tumor cells for neuroendocrine antigens, the detection of GFAP-positive sustentacular cells and the ultrastructural confirmation of neurosecretory granules substantiated this diagnosis. The clinical, radiological and morphological similarity between ependymomas, which are far more common in the cauda equina region than paragangliomas, has led to substantial diagnostic confusion in the past.

Experimental cauda equina compression induces HSP70 synthesis in dog.

The heat shock protein 70 (HSP70) is a key component of the stress response induced by various noxious conditions such as heat, oxygen stress, trauma and infection. In present study we have assessed the consequences of the compression of lower lumbar and sacral nerve roots caused by a multiple cauda equina constrictions (MCEC) on HSP70 immunoreactivity (HSP70-IR) in the dog. Our data indicate that constriction of central processes evokes HSP70 up-regulation in the spinal cord (L7, S1-Co3) as well as in the corresponding dorsal root ganglion cells (DRGs) (L7-S1) two days following injury. A limited number of bipolar or triangular HSP-IR neurons were found in the lateral collateral pathway (LCP) as well as in the pericentral region (lamina X) of the spinal cord. In contrast, a high number of HSP70 exhibiting motoneurons with fine processes appeared in the ventral horn (laminae VIII-IX) of lumbosacral segments. Concomitantly, close to them a few lightly HSP70-positive neuronal somata or cell bodies lacking the HSP70-IR occurred. In the DRGs, HSP70 expression was mildly up-regulated in small and medium-sized neurons and in satellite cells. On the contrary, DRGs from intact or sham-operated dogs did not reveal HSP70 specific neuronal staining. In conclusion, we have demonstrated that the MCEC in dogs mimicking the cauda equina syndrome in clinical settings evokes expression of HSP70 synthesis in specific neurons of the lumbo-sacro-coccygeal spinal cord segments and in small and medium sized neurons of corresponding DRGs. This suggests that HSP70 may play an active role in neuroprotective processes partly by maintaining intracellular protein integrity and preventing the neuronal degeneration in this experimental paradigm.

Cauda equina-derived extracellular matrix for fabrication of nanostructured hybrid scaffolds applied to neural tissue engineering.

Extracellular matrix (ECM) components have become important candidate materials for use as neural scaffolds for neural tissue engineering. In the current study, we prepared cauda equina-derived ECM materials for the production of scaffolds. Natural porcine cauda equina was decellularized using Triton X-100 and sodium deoxycholate, shattered physically, and made into a suspension by differential centrifugation. The decellularization procedure resulted in the removal of >94% of the nuclear material and preserved the extracellular collagen and sulfated glycosaminoglycan. Immunofluorescent staining confirmed the presence of collagen type I, laminin, and fibronectin in the ECM. The cauda equine-derived ECM was blended with poly(l-lactide-co-glycolide) (PLGA) to fabricate nanostructured scaffolds using electrospinning. The incorporation of the ECM increased the hydrophilicity of the scaffolds. Fourier transform infrared spectroscopy and multiphoton-induced autofluorescence images showed the presence of the ECM in the scaffolds. ECM/PLGA scaffolds were beneficial for the survival of Schwann cells compared with scaffolds consisting of PLGA alone, and the aligned fibers could regulate cell morphologic features by modulating cellular orientation. Axons in the dorsal root ganglia explants extended to a greater extent along ECM/PLGA compared with PLGA-alone fibers. The cauda equina ECM might be a promising material for forming scaffolds for use in neural tissue engineering.