Spinal cord injury (SCI) results in paralysis, driven partly by widespread glutamate-induced secondary excitotoxic neuronal cell death in and around the injury site. While there is no curative treatment, the standard of care often requires interventive decompression surgery and repair of the damaged dura mater close to the injury locus using dural substitutes. Such intervention provides an opportunity for early and local delivery of therapeutics directly to the injured cord via a drug-loaded synthetic dural substitute for localized pharmacological therapy. Riluzole, a glutamate-release inhibitor, has shown neuroprotective potential in patients with traumatic SCI, and therefore, this study aimed to develop an electrospun riluzole-loaded synthetic dural substitute patch suitable for the treatment of glutamate-induced injury in neurons. A glutamate-induced excitotoxicity was optimized in SH-SY5Y cells by exploring the effect of glutamate concentration and exposure duration. The most effective timing for administering riluzole was found to be at the onset of glutamate release as this helped to limit extended periods of glutamate-induced excitotoxic cell death. Riluzole-loaded patches were prepared by using blend electrospinning. Physicochemical characterization of the patches showed the successful encapsulation of riluzole within polycaprolactone fibers. A drug release study showed an initial burst release of riluzole within the first 24 h, followed by a sustained release of the drug over 52 days to up to approximately 400 μg released for the highest loading of riluzole within fiber patches. Finally, riluzole eluted from electrospun fibers remained pharmacologically active and was capable of counteracting glutamate-induced excitotoxicity in SH-SY5Y cells, suggesting the clinical potential of riluzole-loaded dural substitutes in counteracting the effects of secondary injury in the injured spinal cord.

• MeSH
• implantované léky MeSH
• kyselina glutamová metabolismus   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• neurony účinky léků   MeSH
• neuroprotektivní látky * aplikace a dávkování   chemie   farmakologie   MeSH
• polyestery chemie   MeSH
• poranění míchy * farmakoterapie   MeSH
• riluzol * aplikace a dávkování   chemie   farmakologie   MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Full recovery from spinal cord injury requires axon regeneration to re-establish motor and sensory pathways. In mammals, the failure of sensory and motor axon regeneration has many causes intrinsic and extrinsic to neurons, amongst which is the lack of adhesion molecules needed to interact with the damaged spinal cord. This study addressed this limitation by expressing the integrin adhesion molecule α9, along with its activator kindlin-1, in sensory neurons via adeno-associated viral (AAV) vectors. This enabled sensory axons to regenerate through spinal cord injuries and extend to the brainstem, restoring sensory pathways, touch sensation and sensory behaviours. One of the integrin ligands in the injured spinal cord is tenascin-C, which serves as a substrate for α9β1 integrin, a key receptor in developmental axon guidance. However, the adult PNS and CNS neurons lack this receptor. Sensory neurons were transduced with α9 integrin (which pairs with endogenous β1 to form a α9β1 tenascin receptor) together with the integrin activator kindlin-1. Regeneration from sensory neurons transduced with α9integrin and kindlin-1 was examined after C4 and after T10 dorsal column lesions with C6,7 and L4,5 sensory ganglia injected with AAV1 vectors. In animals treated with α9 integrin and kindlin-1, sensory axons regenerated through tenascin-C-expressing connective tissue strands and bridges across the lesions and then re-entered the CNS tissue. Many axons regenerated rostrally to the level of the medulla. Axons grew through the dorsal grey matter rather than their normal pathway the dorsal columns. Growth was slow, axons taking 12 weeks to grow from T10 to the medulla, a distance of 4-5 cm. Functional recovery was confirmed through cFos activation in neurons rostral to the injury after nerve stimulation and VGLUT1/2 staining indicating new synapse formation above the lesion. Behavioural recovery was seen in both heat and mechanical sensation, as well as tape removal tests. This approach demonstrates the potential of integrin-based therapies for long distance sensory axon regeneration and functional recovery following thoracic and partial recovery after cervical spinal cord injury.

• MeSH
• axony MeSH
• Dependovirus genetika   MeSH
• genetické vektory MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• nervové receptory * metabolismus   fyziologie   patologie   MeSH
• obnova funkce fyziologie   MeSH
• poranění míchy * patologie   patofyziologie   metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• proteiny nervové tkáně metabolismus   genetika   MeSH
• regenerace nervu * fyziologie   MeSH
• tenascin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Neuropathic pain after spinal cord injury lacks any effective treatments, often leading to chronic pain. This study tested whether the daily administration of fully characterized polyphenolic extracts from grape stalks and coffee could prevent both reflexive and non-reflexive chronic neuropathic pain in spinal cord-injured mice by modulating the neuroimmune axis. Female CD1 mice underwent mild spinal cord contusion and received intraperitoneal extracts in weeks one, three, and six post-surgery. Reflexive pain responses were assessed weekly for up to 10 weeks, and non-reflexive pain was evaluated at the study's end. Neuroimmune crosstalk was investigated, focusing on glial activation and the expression of CCL2/CCR2 and CX3CL1/CX3CR1 in supraspinal pain-related areas, including the periaqueductal gray, rostral ventromedial medulla, anterior cingulate cortex, and amygdala. Repeated treatments prevented mechanical allodynia and thermal hyperalgesia, and also modulated non-reflexive pain. Moreover, they reduced supraspinal gliosis and regulated CCL2/CCR2 and CX3CL1/CX3CR1 signaling. Overall, the combination of polyphenols in these extracts may offer a promising pharmacological strategy to prevent chronic reflexive and non-reflexive pain responses by modifying central sensitization markers, not only at the contusion site but also in key supraspinal regions implicated in neuropathic pain. Overall, these data highlight the potential of polyphenolic extracts for spinal cord injury-induced chronic neuropathic pain.

• MeSH
• chemokin CCL2 metabolismus   MeSH
• chemokin CX3CL1 metabolismus   MeSH
• CX3C chemokinový receptor 1 metabolismus   MeSH
• glióza * farmakoterapie   metabolismus   MeSH
• hyperalgezie farmakoterapie   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• neuralgie * farmakoterapie   metabolismus   etiologie   prevence a kontrola   MeSH
• polyfenoly * farmakologie   aplikace a dávkování   MeSH
• poranění míchy * komplikace   farmakoterapie   metabolismus   MeSH
• receptory CCR2 metabolismus   MeSH
• rostlinné extrakty * farmakologie   aplikace a dávkování   MeSH
• signální transdukce * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Poranění míchy je spojeno nejen s poruchou citlivosti a hybnosti pod úrovní léze, ale také s dalšími komplikacemi, jako jsou dysfunkce autonomního nervového systému, spasticita nebo neuropatické bolesti. Zatímco u nekompletních míšních lézí se daří intenzivní rehabilitací zmírnit neurologický deficit, u klinicky kompletních lézí se neurologický obraz zásadně nemění. V posledních letech se zkoumá potenciál epidurální míšní stimulace, která se ukazuje jako slibná metoda schopná ztracené funkce i u kompletních míšních lézí částečně obnovit. V souborném referátu mapujeme rozvoj metody od ovlivnění bolesti až po obnovení volní hybnosti s využitím digitálního mostu mezi motorickou kůrou a míšním stimulátorem. Během posledních 20 let došlo k významnému posunu od mírného zlepšení hybnosti u nekompletních lézí až po obnovení stoje i chůze u motoricky kompletních poranění. Součástí práce je také souhrn ovlivnění autonomních funkcí s efektem na kardiovaskulární systém, vyprazdňování či sexuální funkce. Limitem uvedených studií je především heterogenita nastavení programů, malé soubory pacientů a také rizika spojená s implantací stimulátoru. I tak představuje epidurální míšní stimulace významný posun v léčbě míšního poranění s pozitivním vlivem na kvalitu života této populace.

Spinal cord injury is associated not only with sensory and motor impairment below the level of the lesion, but also with other complications such as autonomic nervous system dysfunction, spasticity, or neuropathic pain. While intensive rehabilitation can alleviate neurological deficits in incomplete spinal cord lesions, the neurological picture in clinically complete lesions remains fundamentally unchanged. In recent years, the potential of epidural spinal cord stimulation has been investigated, showing promise as a method capable of partially restoring lost function even in complete spinal cord lesions. This review outlines the development of the method, from pain modulation to the restoration of voluntary movement using a digital bridge between the motor cortex and spinal cord stimulator. Over the past twenty years, significant progress has been made from slight improvement in mobility in incomplete lesions to the restoration of standing and walking in motor complete injuries. The work also includes a summary of the effects on autonomic functions, with impacts on the cardiovascular system, bladder control, and sexual functions. The limitations of these studies are primarily the heterogeneity of program settings, small patient cohorts, and the risks associated with stimulator implantation. Nevertheless, epidural spinal cord stimulation represents a significant advance in the treatment of spinal cord injury, with a positive impact on the quality of life for this population.

• MeSH
• autonomní nervový systém MeSH
• elektrostimulační terapie metody   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• míšní stimulace * metody   MeSH
• obnova funkce MeSH
• paraplegie terapie   MeSH
• poranění míchy * terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: Spinal cord injury results in permanent neurological impairment and disability due to the absence of spontaneous regeneration. NG101, a recombinant human antibody, neutralises the neurite growth-inhibiting protein Nogo-A, promoting neural repair and motor recovery in animal models of spinal cord injury. We aimed to evaluate the efficacy of intrathecal NG101 on recovery in patients with acute cervical traumatic spinal cord injury. METHODS: This randomised, double-blind, placebo-controlled phase 2b clinical trial was done at 13 hospitals in the Czech Republic, Germany, Spain, and Switzerland. Patients aged 18-70 years with acute, complete or incomplete cervical spinal cord injury (neurological level of injury C1-C8) within 4-28 days of injury were eligible for inclusion. Participants were initially randomly assigned 1:1 to intrathecal treatment with 45 mg NG101 or placebo (phosphate-buffered saline); 18 months into the study, the ratio was adjusted to 3:1 to achieve a final distribution of 2:1 to improve enrolment and drug exposure. Randomisation was done using a centralised, computer-based randomisation system and was stratified according to nine distinct outcome categories with a validated upper extremity motor score (UEMS) prediction model based on clinical parameters at screening. Six intrathecal injections were administered every 5 days over 4 weeks, starting within 28 days of injury. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was change in UEMS at 6 months, analysed alongside safety in the full analysis set. The completed trial was registered at ClinicalTrials.gov, NCT03935321. FINDINGS: From May 20, 2019, to July 20, 2022, 463 patients with acute traumatic cervical spinal cord injury were screened, 334 were deemed ineligible and excluded, and 129 were randomly assigned to an intervention (80 patients in the NG101 group and 49 in the placebo group). The full analysis set comprised 78 patients from the NG101 group and 48 patients from the placebo group. 107 (85%) patients were male and 19 (15%) patients were female, with a median age of 51·5 years (IQR 30·0-60·0). Across all patients, the primary endpoint showed no significant difference between groups (with UEMS change at 6 months 1·37 [95% CI -1·44 to 4·18]; placebo group mean 19·20 [SD 11·78] at baseline and 30·91 [SD 15·49] at day 168; NG101 group mean 18·23 [SD 15·14] at baseline and 31·31 [19·54] at day 168). Treatment-related adverse events were similar between groups (nine in the NG101 group and six in the placebo group). 25 severe adverse events were reported: 18 in 11 (14%) patients in the NG101 group and seven in six (13%) patients in the placebo group. Although no treatment-related fatalities were reported in the NG101 group, one fatality not related to treatment occurred in the placebo group. Infections were the most common adverse event affecting 44 (92%) patients in the placebo group and 65 (83%) patients in the NG101 group. INTERPRETATION: NG101 did not improve UEMS in patients with acute spinal cord injury. Post-hoc subgroup analyses assessing UEMS and Spinal Cord Independence Measure of self-care in patients with motor-incomplete injury indicated potential beneficial effects that require investigation in future studies. FUNDING: EU program Horizon2020; Swiss State Secretariat for Education, Research and Innovation; Wings for Life; the Swiss Paraplegic Foundation; and the CeNeReg project of Wyss Zurich (University of Zurich and Eidgenössische Technische Hochschule Zurich).

• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• krční mícha * zranění   MeSH
• krční obratle MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Nogo proteiny * MeSH
• poranění míchy * farmakoterapie   MeSH
• senioři MeSH
• spinální injekce * MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Neurons in the CNS lose regenerative potential with maturity, leading to minimal corticospinal tract (CST) axon regrowth after spinal cord injury (SCI). In young rodents, knockdown of PTEN, which antagonizes PI3K signaling by hydrolyzing PIP3, promotes axon regeneration following SCI. However, this effect diminishes in adults, potentially due to lower PI3K activation leading to reduced PIP3. This study explores whether increased PIP3 generation can promote long-distance regeneration in adults. We used a hyperactive PI3K, PI3Kδ (PIK3CD), to boost PIP3 levels in mature cortical neurons and assessed CST regeneration after SCI. Adult rats received AAV1-PIK3CD and AAV1-eGFP, or AAV1-eGFP alone, in the sensorimotor cortex concurrent with a C4 dorsal SCI. Transduced neurons showed increased pS6 levels, indicating elevated PI3K/Akt/mTOR signaling. CST regeneration, confirmed with retrograde tracing, was evaluated up to 16 weeks post injury. At 12 weeks, ∼100 axons were present at lesion sites, doubling to 200 by 16 weeks, with regeneration indices of 0.1 and 0.2, respectively. Behavioral tests showed significant improvements in paw reaching, grip strength, and ladder-rung walking in PIK3CD-treated rats, corroborated by electrophysiological recordings of cord dorsum potentials and distal flexor muscle electromyography. Thus, PI3Kδ upregulation in adult cortical neurons enhances axonal regeneration and functional recovery post SCI.

• MeSH
• axony metabolismus   fyziologie   MeSH
• Dependovirus genetika   MeSH
• fosfatidylinositol-3-kinasy třídy I metabolismus   genetika   MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• genetické vektory genetika   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• neurony metabolismus   MeSH
• obnova funkce MeSH
• poranění míchy * metabolismus   terapie   genetika   MeSH
• pyramidové dráhy * metabolismus   MeSH
• regenerace nervu * MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Poranění míchy je jedním z nejzávažnějších zdravotních postižení zasahujících do řady fyziologických systémů organismu. Péče o spinální pacienty je náročná, vyžaduje multidisciplinární přístup a specializovanou péči. Z tohoto důvodu v ČR vzniká spinální program, který funguje již více než 20 let. Správná urologická péče je důležitá již záhy po poranění. Během pobytu na spinálních rehabilitačních jednotkách je "upravována na míru" danému jedinci. Vždy vychází z důkladného urologického vyšetření, funkčních a kognitivních schopností pacienta. Spolupráce mezi rehabilitačním týmem a urologem je zásadní. Při propuštění z rehabilitačního ústavu je pacient nastaven na bezpečný způsob derivace močového měchýře, edukován v základní problematice neurogenního močového měchýře a možných komplikacích. Zdůrazněna je nutnost celoživotní urologické dispenzarizační péče.

Spinal cord injury is one of the most serious disabilities interfering with a number of the body's physiological systems. The management of spinal patients is challenging, requiring a multidisciplinary approach and specialized care. For this reason, a spinal programme has been established in the Czech Republic for more than 20 years. Proper urological care is important immediately after the injury. During the stay at spinal rehabilitation units, it is tailored to the particular individual. It is always based on a thorough urological evaluation as well as functional and cognitive abilities of the patient. Collaboration between the rehabilitation team and urologist is essential. On discharge from the rehabilitation facility, the patient is put on a safe method of urinary diversion and educated in the basic issues of neurogenic bladder and potential complications. The need for lifelong urological surveillance is emphasized.

• MeSH
• ergoterapie metody   MeSH
• infekce močového ústrojí diagnóza   farmakoterapie   MeSH
• intermitentní katetrizace metody   MeSH
• komplexní zdravotní péče MeSH
• lidé MeSH
• neurogenní močový měchýř rehabilitace   terapie   MeSH
• poranění míchy * etiologie   komplikace   rehabilitace   MeSH
• rehabilitace metody   MeSH
• rehabilitační jednotky MeSH
• vzdělávání pacientů jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• komentáře MeSH

BACKGROUND: The recovery of autonomic functions and the ability to reproduce in particular is of the highest priority to individuals with spinal cord injury (SCI). The potential of epidural spinal cord stimulation (ESCS) for promoting recovery of sensorimotor functions in the chronic phase of SCI has long been studied. In recent years, several studies have emerged confirming the positive effect of ESCS also on the cardiovascular system and neurogenic bladder and bowel. However, the potential of ESCS in restoring sexual function, especially ejaculation, has not yet been addressed. CASE REPORT: Two cases of people with chronic sensorimotor complete SCI in the 4th thoracic spinal segment are presented. Both men were also diagnosed with severe erectile dysfunction and anejaculation. Thanks to ESCS, Participant 1 successfully restored the ejaculatory reflex using PVS in his home environment. His outcome was subsequently verified under clinical conditions. During ESCS, Participant 1 was also able to achieve ejaculation by masturbation; moreover, he conceived a child naturally without the need for IVF. In Participant 2, we then demonstrated the same effect of ESCS on the restoration of the ejaculatory reflex when targeting the stimulation to the same spinal segment. CONCLUSION: This is the first report on the potential of ESCS for restoring the ability to ejaculate in individuals with complete SCI. Confirmation of these results could significantly reduce the need for assisted reproduction and improve the quality of life of men after SCI in the future.

• MeSH
• dospělí MeSH
• ejakulace * fyziologie   MeSH
• epidurální prostor MeSH
• erektilní dysfunkce etiologie   terapie   patofyziologie   MeSH
• hrudní obratle MeSH
• lidé MeSH
• míšní stimulace * metody   MeSH
• poranění míchy * komplikace   patofyziologie   terapie   rehabilitace   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Spinal cord injury (SCI) often leads to central neuropathic pain, a condition associated with significant morbidity and is challenging in terms of the clinical management. Despite extensive efforts, identifying effective biomarkers for neuropathic pain remains elusive. Here we propose a novel approach combining matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with artificial neural networks (ANNs) to discriminate between mass spectral profiles associated with chronic neuropathic pain induced by SCI in female mice. Functional evaluations revealed persistent chronic neuropathic pain following mild SCI as well as minor locomotor disruptions, confirming the value of collecting serum samples. Mass spectra analysis revealed distinct profiles between chronic SCI and sham controls. On applying ANNs, 100% success was achieved in distinguishing between the two groups through the intensities of m/z peaks. Additionally, the ANNs also successfully discriminated between chronic and acute SCI phases. When reflexive pain response data was integrated with mass spectra, there was no improvement in the classification. These findings offer insights into neuropathic pain pathophysiology and underscore the potential of MALDI-TOF MS coupled with ANNs as a diagnostic tool for chronic neuropathic pain, potentially guiding attempts to discover biomarkers and develop treatments.

• MeSH
• biologické markery krev   MeSH
• chronická bolest krev   diagnóza   etiologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• neuralgie * krev   diagnóza   etiologie   MeSH
• neuronové sítě * MeSH
• poranění míchy * komplikace   krev   MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice * metody   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Poranění míchy s sebou přináší řadu trvalých zdravotních následků, které se díky špatnému životnímu stylu a stárnutí zhoršují. Jedním z nich jsou i gastrointestinální komplikace, které se výrazně promítají do problematiky zdraví a kvality života pacientů. Hlavním cílem článku je zhodnotit účinnost viscerální masáže na redukci gastrointestinálních obtíží u chronických pacientů se spinální lézí. K objektivizaci výsledků studie byly využity české verze standardizovaných dotazníků Neurogenic Bowel Dysfunction score (NBD score) a Irritable Bowel Syndrome – Quality of Life survey (IBS-QOL) a nestandardizované české verze dotazníku Burwood Bowel Dysfunction. Hodnocení bylo doplněno i informacemi z anamnestických rozhovorů. Kazuistika prokázala pozitivní vliv viscerální masáže na snížení hodnoty NBD score a subjektivního vnímání bolesti a diskomfortu břicha, ovlivnění frekvence vyprazdňování, množství a konzistence stolice i fekální inkontinence. Fyzioterapeuti by neměli v klinické praxi opomíjet vyšetřovat a ošetřovat gastrointestinální obtíže u subpopulace chronických spinálních pacientů. Nicméně, jejich stav je přednostně ovlivněn dodržováním dietních opatření, optimálního managementu vyprazdňování a zásad zdravého životního stylu.

People with spinal cord injury have a number of permanent health problems that get worse during the bad lifestyle and aging. Among them there are gastrointestinal complications, which have a significant negative impact on health, quality of life and well-being of patients. The purpose of this case study was to determine the efficacy of visceral massage in reducing the severity of bowel dysfunction symptoms of chronic patients with spinal cord injury. The standardized questionnaire Neurogenic Bowel Dysfunction score (NBD score), the standardized questionnaire Irritable Bowel Syndrome – Quality of Life survey (IBS-QOL) and non-standardized Czech version questionnaire Burwood Questionnaire were used to objectify the study results. The assessment was added with information from the anamnestic interviews. This case study demonstrated the positive impact of visceral massage on the reduction of NBD score, abdominal pain and discomfort. Defecation characteristics were positively changed, too (frequency, amount, consistency, faecal incontinence). Physiotherapists should not neglect the need for diagnosis and therapy of gastrointestinal problems in persons with spinal cord injury in clinical practice. However, this issue also depends on the patient‘s compliance with dietary measures, optimal bowel management and healthy lifestyle.

• MeSH
• dospělí MeSH
• gastrointestinální nemoci * etiologie   patologie   terapie   MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• masáž * klasifikace   metody   MeSH
• neurogenní střevo patologie   MeSH
• poranění míchy komplikace   MeSH
• průzkumy a dotazníky MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH