Ependymal cells, a dormant population of ciliated progenitors found within the central canal of the spinal cord, undergo significant alterations after spinal cord injury (SCI). Understanding the molecular events that induce ependymal cell activation after SCI represents the first step toward controlling the response of the endogenous regenerative machinery in damaged tissues. This response involves the activation of specific signaling pathways in the spinal cord that promotes self-renewal, proliferation, and differentiation. We review our current understanding of the signaling pathways and molecular events that mediate the SCI-induced activation of ependymal cells by focusing on the roles of some cell adhesion molecules, cellular membrane receptors, ion channels (and their crosstalk), and transcription factors. An orchestrated response regulating the expression of receptors and ion channels fine-tunes and coordinates the activation of ependymal cells after SCI or cell transplantation. Understanding the major players in the activation of ependymal cells may help us to understand whether these cells represent a critical source of cells contributing to cellular replacement and tissue regeneration after SCI. A more complete understanding of the role and function of individual signaling pathways in endogenous spinal cord progenitors may foster the development of novel targeted therapies to induce the regeneration of the injured spinal cord.

• MeSH
• ependym metabolismus   MeSH
• iontové kanály metabolismus   MeSH
• lidé MeSH
• mícha MeSH
• neuroglie metabolismus   MeSH
• poranění míchy * terapie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy 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

More than half of spinal cord injury (SCI) patients develop central neuropathic pain (CNP), which is largely refractory to current treatments. Considering the preclinical evidence showing that polyphenolic compounds may exert antinociceptive effects, the present work aimed to study preventive effects on SCI-induced CNP development by repeated administration of two vegetal polyphenolic extracts: grape stalk extract (GSE) and coffee extract (CE). Thermal hyperalgesia and mechanical allodynia were evaluated at 7, 14 and 21 days postinjury. Then, gliosis, ERK phosphorylation and the expression of CCL2 and CX3CL1 chemokines and their receptors, CCR2 and CX3CR1, were analyzed in the spinal cord. Gliosis and CX3CL1/CX3CR1 expression were also analyzed in the anterior cingulate cortex (ACC) and periaqueductal gray matter (PAG) since they are supraspinal structures involved in pain perception and modulation. GSE and CE treatments modulated pain behaviors accompanied by reduced gliosis in the spinal cord and both treatments modulated neuron-glia crosstalk-related biomolecules expression. Moreover, both extracts attenuated astrogliosis in the ACC and PAG as well as microgliosis in the ACC with an increased M2 subpopulation of microglial cells in the PAG. Finally, GSE and CE prevented CX3CL1/CX3CR1 upregulation in the PAG, and modulated their expression in ACC. These findings suggest that repeated administrations of either GSE or CE after SCI may be suitable pharmacologic strategies to attenuate SCI-induced CNP development by means of spinal and supraspinal neuroinflammation modulation.

• MeSH
• glióza komplikace   etiologie   MeSH
• hyperalgezie komplikace   etiologie   MeSH
• mícha metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední ICR MeSH
• myši MeSH
• neuralgie * komplikace   etiologie   MeSH
• poranění míchy * komplikace   farmakoterapie   metabolismus   MeSH
• Vitis * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Investigating the molecular mechanisms governing developmental axon growth has been a useful approach for identifying new strategies for boosting axon regeneration after injury, with the goal of treating debilitating conditions such as spinal cord injury and vision loss. The picture emerging is that various axonal organelles are important centers for organizing the molecular mechanisms and machinery required for growth cone development and axon extension, and these have recently been targeted to stimulate robust regeneration in the injured adult central nervous system (CNS). This review summarizes recent literature highlighting a central role for organelles such as recycling endosomes, the endoplasmic reticulum, mitochondria, lysosomes, autophagosomes and the proteasome in developmental axon growth, and describes how these organelles can be targeted to promote axon regeneration after injury to the adult CNS. This review also examines the connections between these organelles in developing and regenerating axons, and finally discusses the molecular mechanisms within the axon that are required for successful axon growth.

• MeSH
• lidé MeSH
• organely metabolismus   patologie   MeSH
• poranění míchy * metabolismus   patologie   terapie   MeSH
• regenerace nervu * MeSH
• růstové kužele metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

MicroRNAs (miRNA) are short (~22 nucleotides in length), non-coding RNAs that regulate gene expression by binding to specific mRNA targets and promoting their degradation and/or translational inhibition. MicroRNAs circulating in the peripheral blood are reported to modulate signaling between cells, to be diagnostic markers for cancers and are also acknowledged as an important player in the pathophysiology of spinal cord injury (SCI). Recent studies suggest that changes in gene expression following neural injury can result from the dysregulation of miRNAs, which play important roles in diverse neurobiological processes such as: cell differentiation, growth, proliferation and neuronal activity, as well as the pathogenic processes of central nervous system (CNS) injury including inflammation, oxidation, demyelination and apoptosis. The severity of the initial injury plays a significant role in determining the nature and amplitude of the secondary injury and consequently the appropriate interventions. However, current clinical measures for characterizing injury se-verity are based on functional tests that cannot be applied immediately following injury because they are often compromised by shock, other attendant injuries and drugs or alcohol. Neural stem cells are recognized as the most promising natural resource for the treatment of CNS diseases due to their proliferation, renewal, and passage capacities in vivo and in vitro. Recent studies have shown that transplan-ted stem cells confer neuroprotection primarily through a paracrine mechanism, and small extracellular vesicles play an important role in this process; they have been proposed to serve as an ideal carrier to deliver miRNAs to recipient cells. This mini-review summarizes new insights into the role of miRNAs in the pathophysiology, diagnosis, and treatment of SCI.

• MeSH
• lidé MeSH
• mikro RNA analýza   fyziologie   MeSH
• poranění míchy * genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Tables for calculating the energy expenditure of the physical activities of the general population cannot be used due to the different paralysis of the upper or lower limbs in people with spinal cord injury (SCI). The purpose of this review is to compare the differences in the values of basal metabolic rate (BMR), basal energy expenditure (BEE), resting energy expenditure (REE) and resting metabolic rate (RMR) the values evidenced in the literature, observed values vs predicted values using the Harris-Benedict equation. We realized the background research from the time period from 1985 to 2018. We searched in PubMed, Web of Science and Scopus databases for articles addressing the relationship between BMR and people with SCI. We compared the parameters of BMR, BEE, REE and RMR according to Harris-Benedict (HB) equation for persons with SCI. The study confirmed that the energy expenditure of persons with SCI could not be evaluated correctly by the Harris-Benedict equation.

• MeSH
• antropometrie metody   MeSH
• bazální metabolismus fyziologie   MeSH
• databáze bibliografické MeSH
• energetický metabolismus * MeSH
• lidé MeSH
• nepřímá kalorimetrie metody   přístrojové vybavení   MeSH
• paraplegie metabolismus   MeSH
• poranění míchy metabolismus   MeSH
• prediktivní hodnota testů MeSH
• tuková tkáň metabolismus   MeSH
• věkové rozložení MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• systematický přehled MeSH

A highly water soluble, nano-formulated curcumin was used for the treatment of the experimental model of spinal cord injury (SCI) in rats. Nanocurcumin and a vehicle nanocarrier as a control, were delivered both locally, immediately after the spinal cord injury, and intraperitoneally during the 4 consecutive weeks after SCI. The efficacy of the treatment was assessed using behavioral tests, which were performed during the experiment, weekly for 9 weeks. The behavioral tests (BBB, flat beam test, rotarod, motoRater) revealed a significant improvement in the nanocurcumin treated group, compared to the nanocarrier control. An immunohistochemical analysis of the spinal cord tissue was performed at the end of the experiment and this proved a significant preservation of the white matter tissue, a reduced area of glial scaring and a higher amount of newly sprouted axons in the nanocurcumin treated group. The expression of endogenous genes (Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, Nfkβ) and interleukins (IL-1β, TNF-α, IL-6, IL-12, CCL-5, IL-11, IL-10, IL-13) was evaluated by qPCR and showed changes in the expression of the inflammatory cytokines in the first two weeks after SCI.

• MeSH
• bílá hmota účinky léků   metabolismus   patologie   MeSH
• jizva farmakoterapie   metabolismus   patologie   MeSH
• krysa rodu rattus MeSH
• kurkumin aplikace a dávkování   MeSH
• mediátory zánětu antagonisté a inhibitory   metabolismus   MeSH
• nanočástice aplikace a dávkování   MeSH
• neuroglie účinky léků   metabolismus   patologie   MeSH
• poranění míchy farmakoterapie   metabolismus   patologie   MeSH
• potkani Wistar MeSH
• příprava léků MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The study aimed to determine the effects of protease-activated receptor-2 (PAR-2) on glial scar formation after spinal cord injury (SCI) in Sprague-Dawley (SD) rats and the underlying mechanisms. Rivlin and Tator's acute extradural clip compression injury (CCI) model of severe SCI was established in this study. Animals were divided into four groups: 1) sham group (laminectomy only); 2) model group, treated with normal saline; 3) PAR-2 inhibitor group; 4) PAR-2 activator group. Enhanced GFAP and vimentin expression were the markers of glial scar formation. To determine whether JNK was involved in the effects of PAR-2 on GFAP and vimentin expression, we administered anisomycin (a JNK activator) in the presence of PAR-2 inhibitor and SP600125 (a JNK inhibitor) in the presence of PAR-2 activator. At 1, 7, 14 and 28 day after SCI, Basso, Beattie, and Bresnahan (BBB) locomotor score test was used to assess the locomotor functional recovery; immunofluorescence and western blot analysis were used to assess the expression level of GFAP, vimentin and p-JNK. Double immunofluorescence staining with GFAP and tubulin beta was used to assess the glial scar formation and the remaining neurons. Results suggested that PAR-2 is involved in glial scar formation and reduces neurons residues which can cause a further worsening in the functional outcomes after SCI via JNK signaling. Therefore, it may be effective to target PAR-2 in the treatment of SCI.

• MeSH
• anisomycin farmakologie   MeSH
• anthraceny farmakologie   MeSH
• jizva metabolismus   patologie   prevence a kontrola   MeSH
• krysa rodu rattus MeSH
• MAP kinasový signální systém účinky léků   fyziologie   MeSH
• poranění míchy metabolismus   patologie   MeSH
• potkani Sprague-Dawley MeSH
• receptor PAR-2 antagonisté a inhibitory   biosyntéza   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• lidé MeSH
• poranění míchy metabolismus   patologie   terapie   MeSH
• regenerace nervu MeSH
• translační biomedicínský výzkum metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• úvodní články MeSH
• úvodníky MeSH

Methacrylate hydrogels have been extensively used as bridging scaffolds in experimental spinal cord injury (SCI) research. As synthetic materials, they can be modified, which leads to improved bridging of the lesion. Fibronectin, a glycoprotein of the extracellular matrix produced by reactive astrocytes after SCI, is known to promote cell adhesion. We implanted 3 methacrylate hydrogels: a scaffold based on hydroxypropylmethacrylamid (HPMA), 2-hydroxyethylmethacrylate (HEMA) and a HEMA hydrogel with an attached fibronectin (HEMA-Fn) in an experimental model of acute SCI in rats. The animals underwent functional evaluation once a week and the spinal cords were histologically assessed 3 months after hydrogel implantation. We found that both the HPMA and the HEMA-Fn hydrogel scaffolds lead to partial sensory improvement compared to control animals and animals treated with plain HEMA scaffold. The HPMA scaffold showed an increased connective tissue infiltration compared to plain HEMA hydrogels. There was a tendency towards connective tissue infiltration and higher blood vessel ingrowth in the HEMA-Fn scaffold. HPMA hydrogels showed a significantly increased axonal ingrowth compared to HEMA-Fn and plain HEMA; while there were some neurofilaments in the peripheral as well as the central region of the HEMA-Fn scaffold, no neurofilaments were found in plain HEMA hydrogels. In conclusion, HPMA hydrogel as well as the HEMA-Fn scaffold showed better bridging qualities compared to the plain HEMA hydrogel, which resulted in very limited partial sensory improvement.

• MeSH
• axony fyziologie   MeSH
• biokompatibilní materiály MeSH
• biologické markery MeSH
• exprese genu MeSH
• extracelulární matrix metabolismus   MeSH
• fyziologická neovaskularizace MeSH
• hematoencefalická bariéra metabolismus   MeSH
• hojení ran MeSH
• hydrogely * MeSH
• krysa rodu rattus MeSH
• methakryláty * chemie   MeSH
• modely nemocí na zvířatech MeSH
• pojivová tkáň MeSH
• poranění míchy etiologie   metabolismus   patologie   terapie   MeSH
• regenerace nervu * MeSH
• tkáňové podpůrné struktury MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH