Syndrom kaudy equiny (cauda equina syndrome; CES) patří mezi onemocnění s potenciálně vysokou neurologickou morbiditou. Pacienti přicházejí s různě vyjádřeným neurologickým deficitem, zahrnujícím zejména sfinkterové potíže, který je nutné včasně diagnostikovat a správně indikovat chirurgickou léčbu. V naší retrospektivní studii jsme se zaměřili na různé prognostické faktory a jejich vliv na výsledný neurologický stav pacientů s CES. Do studie bylo zařazeno celkově 44 pacientů s CES. Statisticky významným faktorem se ukázala doba trvání příznaků. Pacienti s kratší anamnézou neurologické symptomatologie měli lepší výsledný neurologický stav. Také je průkazně pozitivní vztah mezi vstupním a výstupním skóre, tedy výsledný stav se odvíjí od tíže neurologického deficitu při přijetí pacienta. Ostatní faktory byly statisticky nevýznamné.
Cauda equina syndrome (CES) is a severe neurological condition with potentially high morbidity. Patients usually present with varying degrees of neurological deficit, especially sphincter dysfunction, which needs to be diagnosed early and correctly indicated for surgical treatment. Our retrospective study is focused on the determination of different prognostic factors and their impact on the final neurological outcome of patients with CES. Forty-four CES patients were recruited in the study. The duration of symptoms has proven to be a statistically significant factor in improving the clinical condition. Patients with a shorter medical history of neurological symptomatology had a better neurological outcome. Also, there was a positive relationship between the initial and outcome score, i.e., the outcome status is related to the severity of the neurological deficit on admission. The remaining factors appeared to be statistically insignificant.
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.
- MeSH
- adhezní molekula epiteliálních buněk MeSH
- cauda equina * metabolismus patologie chirurgie MeSH
- claudin-4 MeSH
- lidé MeSH
- lokální recidiva nádoru patologie MeSH
- nádory centrálního nervového systému * patologie MeSH
- neuroendokrinní nádory * patologie MeSH
- paragangliom * MeSH
- represorové proteiny MeSH
- transkripční faktory MeSH
- tyrosin-3-monooxygenasa MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The peripheral branch of sensory dorsal root ganglion (DRG) neurons regenerates readily after injury unlike their central branch in the spinal cord. However, extensive regeneration and reconnection of sensory axons in the spinal cord can be driven by the expression of α9 integrin and its activator kindlin-1 (α9k1), which enable axons to interact with tenascin-C. To elucidate the mechanisms and downstream pathways affected by activated integrin expression and central regeneration, we conducted transcriptomic analyses of adult male rat DRG sensory neurons transduced with α9k1, and controls, with and without axotomy of the central branch. Expression of α9k1 without the central axotomy led to upregulation of a known PNS regeneration program, including many genes associated with peripheral nerve regeneration. Coupling α9k1 treatment with dorsal root axotomy led to extensive central axonal regeneration. In addition to the program upregulated by α9k1 expression, regeneration in the spinal cord led to expression of a distinctive CNS regeneration program, including genes associated with ubiquitination, autophagy, endoplasmic reticulum (ER), trafficking, and signaling. Pharmacological inhibition of these processes blocked the regeneration of axons from DRGs and human iPSC-derived sensory neurons, validating their causal contributions to sensory regeneration. This CNS regeneration-associated program showed little correlation with either embryonic development or PNS regeneration programs. Potential transcriptional drivers of this CNS program coupled to regeneration include Mef2a, Runx3, E2f4, and Yy1. Signaling from integrins primes sensory neurons for regeneration, but their axon growth in the CNS is associated with an additional distinctive program that differs from that involved in PNS regeneration.SIGNIFICANCE STATEMENT Restoration of neurologic function after spinal cord injury has yet to be achieved in human patients. To accomplish this, severed nerve fibers must be made to regenerate. Reconstruction of nerve pathways has not been possible, but recently, a method for stimulating long-distance axon regeneration of sensory fibers in rodents has been developed. This research uses profiling of messenger RNAs in the regenerating sensory neurons to discover which mechanisms are activated. This study shows that the regenerating neurons initiate a novel CNS regeneration program which includes molecular transport, autophagy, ubiquitination, and modulation of the endoplasmic reticulum (ER). The study identifies mechanisms that neurons need to activate to regenerate their nerve fibers.
- MeSH
- axony * fyziologie MeSH
- integriny metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mícha metabolismus MeSH
- nervové receptory fyziologie MeSH
- poranění míchy * terapie metabolismus MeSH
- potkani Sprague-Dawley MeSH
- regenerace nervu fyziologie MeSH
- spinální ganglia metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Klíčová slova
- meningeální syndrom,
- MeSH
- hlavové nervy patofyziologie patologie MeSH
- lidé MeSH
- meningy * diagnostické zobrazování patofyziologie patologie MeSH
- míšní kořeny patofyziologie patologie MeSH
- mozkomíšní mok fyziologie MeSH
- neurologické vyšetření metody MeSH
- syndrom MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Nucleolin is a multifunctional RNA Binding Protein (RBP) with diverse subcellular localizations, including the nucleolus in all eukaryotic cells, the plasma membrane in tumor cells, and the axon in neurons. Here we show that the glycine arginine rich (GAR) domain of nucleolin drives subcellular localization via protein-protein interactions with a kinesin light chain. In addition, GAR sequences mediate plasma membrane interactions of nucleolin. Both these modalities are in addition to the already reported involvement of the GAR domain in liquid-liquid phase separation in the nucleolus. Nucleolin transport to axons requires the GAR domain, and heterozygous GAR deletion mice reveal reduced axonal localization of nucleolin cargo mRNAs and enhanced sensory neuron growth. Thus, the GAR domain governs axonal transport of a growth controlling RNA-RBP complex in neurons, and is a versatile localization determinant for different subcellular compartments. Localization determination by GAR domains may explain why GAR mutants in diverse RBPs are associated with neurodegenerative disease.
- MeSH
- axonální transport genetika MeSH
- buněčné jadérko metabolismus ultrastruktura MeSH
- exprese genu MeSH
- fosfoproteiny chemie genetika metabolismus MeSH
- HEK293 buňky MeSH
- HeLa buňky MeSH
- kineziny genetika metabolismus MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- mutace MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nervus ischiadicus cytologie metabolismus MeSH
- neurony cytologie metabolismus MeSH
- primární buněčná kultura MeSH
- proteinové domény MeSH
- proteiny vázající RNA chemie genetika metabolismus MeSH
- sekvence aminokyselin MeSH
- spinální ganglia cytologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Chronic pain is regarded to be one of the common and refractory diseases to cure in the clinic. One hundred Hz electroacupuncture (EA) is commonly used for inflammatory pain and 2 Hz for neuropathic pain possibly by modulating the transient receptor potential vanilloid subtype 1 (TRPV1) or the purinergic P2X3 related pathways. To clarify the mechanism of EA under various conditions of pathological pain, rats received a subcutaneous administration of complete Freund's adjuvant (CFA) for inflammatory pain and spared nerve injury (SNI) for neuropathic pain. The EA was performed at the bilateral ST36 and BL60 1 d after CFA or SNI being successfully established for 3 consecutive days. The mechanical hyperalgesia test was measured at baseline, 1 d after model establishment, 1 d and 3 d after EA. The co-expression changes, co-immunoprecipitation of TRPV1 and P2X3, and spontaneous pain behaviors (SPB) test were performed 3 d after EA stimulation. One hundred Hz EA or 2Hz EA stimulation could effectively down-regulate the hyperalgesia of CFA or SNI rats. The increased co-expression ratio between TRPV1 and P2X3 at the dorsal root ganglion (DRG) in two types of pain could be reduced by 100Hz or 2Hz EA intervention. While 100Hz or 2Hz EA was not able to eliminate the direct physical interaction between TRPV1 and P2X3. Moreover, EA could significantly inhibit the SPB induced by the co-activation of peripheral TRPV1 and P2X3. All results indicated that EA could significantly reduce the hyperalgesia and the SPB, which was partly related to inhibiting the co-expression and indirect interaction between peripheral TRPV1 and P2X3.
- MeSH
- elektroakupunktura * MeSH
- hyperalgezie metabolismus patofyziologie terapie MeSH
- kationtové kanály TRPV metabolismus MeSH
- modely nemocí na zvířatech MeSH
- neuralgie metabolismus patofyziologie terapie MeSH
- potkani Sprague-Dawley MeSH
- práh bolesti MeSH
- purinergní receptory P2X3 metabolismus MeSH
- signální transdukce MeSH
- spinální ganglia metabolismus patofyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
ABSTRACT: MR tractography of the lumbosacral plexus (LSP) is challenging due to the difficulty of acquiring high quality data and accurately estimating the neuronal tracts. We proposed an algorithm for an accurate visualization and assessment of the major LSP bundles using the segmentation of the cauda equina as seed points for the initial starting area for the fiber tracking algorithm.Twenty-six healthy volunteers underwent MRI examinations on a 3T MR scanner using the phased array coils with optimized measurement protocols for diffusion-weighted images and coronal T2 weighted 3D short-term inversion recovery sampling perfection with application optimized contrast using varying flip angle evaluation sequences used for LSP fiber reconstruction and MR neurography (MRN).The fiber bundles reconstruction was optimized in terms of eliminating the muscle fibers contamination using the segmentation of cauda equina, the effects of the normalized quantitative anisotropy (NQA) and angular threshold on reconstruction of the LSP. In this study, the NQA parameter has been used for fiber tracking instead of fractional anisotropy (FA) and the regions of interest positioning was precisely adjusted bilaterally and symmetrically in each individual subject.The diffusion data were processed in individual L3-S2 nerve fibers using the generalized Q-sampling imaging algorithm. Data (mean FA, mean diffusivity, axial diffusivity and radial diffusivity, and normalized quantitative anisotropy) were statistically analyzed using the linear mixed-effects model. The MR neurography was performed in MedINRIA and post-processed using the maximum intensity projection method to demonstrate LSP tracts in multiple planes.FA values significantly decreased towards the sacral region (P < .001); by contrast, mean diffusivity, axial diffusivity, radial diffusivity and NQA values significantly increased towards the sacral region (P < .001).Fiber tractography of the LSP was feasible in all examined subjects and closely corresponded with the nerves visible in the maximum intensity projection images of MR neurography. Usage of NQA instead of FA in the proposed algorithm enabled better separation of muscle and nerve fibers.The presented algorithm yields a high quality reconstruction of the LSP bundles that may be helpful both in research and clinical practice.
- MeSH
- algoritmy MeSH
- anizotropie MeSH
- cauda equina diagnostické zobrazování MeSH
- difuzní magnetická rezonance metody MeSH
- dospělí MeSH
- lidé MeSH
- lumbosakrální krajina inervace MeSH
- magnetická rezonanční tomografie metody MeSH
- míšní nervy anatomie a histologie diagnostické zobrazování MeSH
- plexus lumbosacralis diagnostické zobrazování MeSH
- počítačové zpracování obrazu metody MeSH
- zobrazování difuzních tenzorů metody MeSH
- zobrazování trojrozměrné přístrojové vybavení MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
In this brief report, we demonstrate that the Cav3.3 T-type voltage-gated calcium channel subtype is involved in our FRICT-ION model of chronic trigeminal neuropathic pain. We first showed that the Cacna1i gene encoding Cav3.3 is significantly upregulated in whole trigeminal ganglia of FRICT-ION mice compared to controls at week 10 post-injury. We confirmed protein upregulation of Cav3.3 compared to controls using Western blot analysis of whole trigeminal ganglia tissues. Finally, we demonstrated that intraperitoneal injection of a selective TAT-based Cav3.3 blocking peptide in FRICT-ION mice significantly reduces Cav3.3 protein expression at the peak anti-allodynic effect (4 hrs post-injection) of the attenuated neuropathic pain behavior. We also suggest that blockade of Cav3.3 may be more effective in attenuating trigeminal neuropathic pain in female than male FRICT-ION mice. Therefore, blocking or attenuating Cav3.3 function may be an effective strategy for the treatment of trigeminal neuropathic pain.
Members of neuropeptide B/W signaling system have been predominantly detected and mapped within the CNS. In the rat, this system includes neuropeptide B (NPB), neuropeptide W (NPW) and their specific receptor NPBWR1. This signaling system has a wide spectrum of functions including a role in modulation of inflammatory pain and neuroendocrine functions. Expression of NPB, NPW and NPBWR1 in separate heart compartments, dorsal root ganglia (DRG) and stellate ganglia was proven by RT-qPCR, Western blot (WB) and immunofluorescence. Presence of mRNA for all tested genes was detected within all heart compartments and ganglia. The presence of proteins preproNPB, preproNPW and NPBWR1 was confirmed in all the chambers of heart by WB. Expression of preproNPW and preproNPB was proven in cardiac ganglionic cells obtained by laser capture microdissection. In immunofluorescence analysis, NPB immunoreactivity was detected in nerve fibers, some nerve cell bodies and smooth muscle within heart and both ganglia. NPW immunoreactivity was present in the nerve cell bodies and nerve fibers of heart ganglia. Weak nonhomogenous staining of cardiomyocytes was present within heart ventricles. NPBWR1 immunoreactivity was detected on cardiomyocytes and some nerve fibers. We confirmed the presence of NPB/W signaling system in heart, DRG and stellate ganglia by proteomic and genomic analyses.
- MeSH
- exprese genu MeSH
- fluorescenční protilátková technika MeSH
- ganglion stellatum metabolismus MeSH
- myokard metabolismus MeSH
- neuropeptidy genetika imunologie metabolismus MeSH
- potkani Zucker MeSH
- receptory neuropeptidů genetika imunologie metabolismus MeSH
- receptory spřažené s G-proteiny genetika imunologie metabolismus MeSH
- reprodukovatelnost výsledků MeSH
- signální transdukce MeSH
- spinální ganglia metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
