• MeSH
• Brownův-Séquardův syndrom diagnóza   etiologie   patofyziologie   MeSH
• centrální míšní syndrom klasifikace   patofyziologie   MeSH
• defekace fyziologie   MeSH
• laterální míšní syndrom klasifikace   patofyziologie   MeSH
• lidé MeSH
• mícha * anatomie a histologie   patofyziologie   MeSH
• míšní ischemie * etiologie   patofyziologie   MeSH
• močení fyziologie   MeSH
• sexuální dysfunkce fyziologická etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Gene silencing with virally delivered shRNA represents a promising approach for treatment of inherited neurodegenerative disorders. In the present study we develop a subpial technique, which we show in adult animals successfully delivers adeno-associated virus (AAV) throughout the cervical, thoracic and lumbar spinal cord, as well as brain motor centers. One-time injection at cervical and lumbar levels just before disease onset in mice expressing a familial amyotrophic lateral sclerosis (ALS)-causing mutant SOD1 produces long-term suppression of motoneuron disease, including near-complete preservation of spinal α-motoneurons and muscle innervation. Treatment after disease onset potently blocks progression of disease and further α-motoneuron degeneration. A single subpial AAV9 injection in adult pigs or non-human primates using a newly designed device produces homogeneous delivery throughout the cervical spinal cord white and gray matter and brain motor centers. Thus, spinal subpial delivery in adult animals is highly effective for AAV-mediated gene delivery throughout the spinal cord and supraspinal motor centers.

• MeSH
• amyotrofická laterální skleróza genetika   patofyziologie   terapie   MeSH
• atrofie MeSH
• degenerace nervu genetika   patofyziologie   terapie   MeSH
• Dependovirus metabolismus   MeSH
• interneurony patologie   MeSH
• lidé MeSH
• malá interferující RNA aplikace a dávkování   MeSH
• messenger RNA genetika   metabolismus   MeSH
• mícha diagnostické zobrazování   patologie   patofyziologie   MeSH
• motorické evokované potenciály MeSH
• motorické neurony patologie   MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• pia mater patologie   patofyziologie   MeSH
• prasata MeSH
• primáti MeSH
• progrese nemoci MeSH
• regulace genové exprese MeSH
• sbalování proteinů MeSH
• superoxid dismutáza 1 genetika   metabolismus   MeSH
• technika přenosu genů * MeSH
• umlčování genů * MeSH
• vývoj svalů MeSH
• zánět patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

BACKGROUND: Spinal cord stimulation (SCS) reduces sympathetic activity in animal models of heart failure with reduced ejection fraction (HF) but limited data exist of SCS in patients with HF. The aim of the present study was to test the primary hypothesis that SCS reduces cardiac sympathetic nerve activity in HF patients. Secondary hypotheses were that SCS improves left ventricular function and dimension, exercise capacity, and clinical variables relevant to HF. METHODS: HF patients with a SCS device previously participating in the DEFEAT-HF trial were included in this crossover study with 6-week intervention periods (SCS-ON and SCS-OFF). SCS (50 Hz, 210-μs pulse duration, aiming at T2-T4 segments) was delivered for 12 hours daily. Indices of myocardial sympathetic neuronal function (heart-to-mediastinum ratio, HMR) and activity (washout rate, WR) were assessed using123I-metaiodobenzylguanidine (MIBG) scintigraphy. Echocardiography, exercise testing, and clinical data collection were also performed. RESULTS: We included 13 patients (65.3 ± 8.0 years, nine males) and MIBG scintigraphy data were available in 10. HMR was not different comparing SCS-ON (1.37 ± 0.16) and SCS-OFF (1.41 ± 0.21, P = 0.46). WR was also unchanged comparing SCS-ON (41.5 ± 5.3) and SCS-OFF (39.1 ± 5.8, P = 0.30). Similarly, average New York Heart Association class (2.4 ± 0.5 vs 2.3 ± 0.6, P = 0.34), quality of life score (24 ± 16 vs 24 ± 16, P = 0.94), and left ventricular dimension and function as well as exercise capacity were all unchanged comparing SCS-ON and SCS-OFF. CONCLUSION: In patients with HF, SCS (12 hours daily, targeting the T2-T4 segments of the spinal cord) does not appear to influence cardiac sympathetic neuronal activity or function as assessed by MIBG scintigraphy.

• MeSH
• lidé MeSH
• mícha diagnostické zobrazování   patofyziologie   MeSH
• míšní stimulace metody   MeSH
• senioři MeSH
• srdce diagnostické zobrazování   inervace   patofyziologie   MeSH
• srdeční selhání patofyziologie   terapie   MeSH
• sympatický nervový systém patofyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus interna is an effective tool for the treatment of dystonia with possible distant effects reaching beyond the basal ganglia network. AIM: We analyzed the cortical silent period (CoSP) to test inhibitory circuits at the cortical level, and the cutaneous silent period (CuSP) and the H-reflex to test inhibitory circuits at the spinal level. METHODS: The upper limb muscles of 16 patients (9F, aged 54±(SD)16years) with generalized (N=9) and cervical (N=7) dystonia treated with DBS bilaterally were examined by the CoSP, CuSP and H-reflex in two states with random order: (i) in DBS ON and (ii) in DBS OFF condition two hours later, and compared with healthy controls. RESULTS: While the CuSP and H-Reflex did not differ between groups and remained unaffected by DBS, the CoSP was influenced significantly in dystonia. The CoSP onset latency was shortened (p<0.05 corrected) and the CoSP duration prolonged (p<0.01 corrected) in ON versus OFF condition. This effect was especially larger in generalized or phasic type of dystonia. Compared to healthy controls, the CoSP latency and duration became shorter in patients during the OFF condition only. CONCLUSION: The pallidal DBS did not affect the spinal inhibitory circuitry in dystonia. However, the abnormally low cortical inhibition was normalized after DBS possibly offering more efficient suppression of aberrant dystonic movements.

• MeSH
• dospělí MeSH
• dystonie terapie   MeSH
• globus pallidus fyziologie   MeSH
• H-reflex fyziologie   MeSH
• hluboká mozková stimulace metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mícha patofyziologie   MeSH
• mladý dospělý MeSH
• motorické evokované potenciály fyziologie   MeSH
• mozková kůra patofyziologie   MeSH
• nervový útlum fyziologie   MeSH
• senioři MeSH
• šířící se kortikální deprese fyziologie   MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Well known for its anti-oxidative and anti-inflammation properties, curcumin is a polyphenol found in the rhizome of Curcuma longa. In this study, we evaluated the effects of curcumin on behavioral recovery, glial scar formation, tissue preservation, axonal sprouting, and inflammation after spinal cord injury (SCI) in male Wistar rats. The rats were randomized into two groups following a balloon compression injury at the level of T9-T10 of the spinal cord, namely vehicle- or curcumin-treated. Curcumin was applied locally on the surface of the injured spinal cord immediately following injury and then given intraperitoneally daily; the control rats were treated with vehicle in the same manner. Curcumin treatment improved behavioral recovery within the first week following SCI as evidenced by improved Basso, Beattie, and Bresnahan (BBB) test and plantar scores, representing locomotor and sensory performance, respectively. Furthermore, curcumin treatment decreased glial scar formation by decreasing the levels of MIP1α, IL-2, and RANTES production and by decreasing NF-κB activity. These results, therefore, demonstrate that curcumin has a profound anti-inflammatory therapeutic potential in the treatment of spinal cord injury, especially when given immediately after the injury.

• MeSH
• antiflogistika farmakologie   MeSH
• imunomodulace * MeSH
• krysa rodu rattus MeSH
• kurkumin farmakologie   MeSH
• mícha patofyziologie   MeSH
• modely nemocí na zvířatech MeSH
• obnova funkce * MeSH
• poranění míchy farmakoterapie   imunologie   patofyziologie   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• antitumorózní látky farmakologie   terapeutické užití   MeSH
• chirurgická dekomprese využití   MeSH
• denosumab * farmakologie   terapeutické užití   MeSH
• humanizované monoklonální protilátky farmakologie   terapeutické užití   MeSH
• inhibitory aromatasy farmakologie   terapeutické užití   MeSH
• komprese míchy chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů * farmakoterapie   MeSH
• mícha chirurgie   patofyziologie   MeSH
• nádory kostí * farmakoterapie   sekundární   MeSH
• nádory prsu * farmakoterapie   komplikace   MeSH
• vitamin D farmakologie   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Gain-of-function (GOF) mutations in ion channels are rare events, which lead to increased agonist sensitivity or altered gating properties, and may render the channel constitutively active. Uncovering and following characterization of such mutants contribute substantially to the understanding of the molecular basis of ion channel functioning. Here we give an overview of some GOF mutants in polymodal ion channels specifically involved in transduction of painful stimuli--TRPV1 and TRPA1, which are scrutinized by scientists due to their important role in development of some pathological pain states. Remarkably, a substitution of single amino acid in the S4-S5 region of TRPA1 (N855S) has been recently associated with familial episodic pain syndrome. This mutation increases chemical sensitivity of TRPA1, but leaves the voltage sensitivity unchanged. On the other hand, mutations in the analogous region of TRPV1 (R557K and G563S) severely affect all aspects of channel activation and lead to spontaneous activity. Comparison of the effects induced by mutations in homologous positions in different TRP receptors (or more generally in other distantly related ion channels) may elucidate the gating mechanisms conserved during evolution.

• MeSH
• bolest patofyziologie   MeSH
• kationtové kanály TRP chemie   genetika   metabolismus   MeSH
• kationtové kanály TRPV chemie   genetika   metabolismus   MeSH
• lidé MeSH
• mícha patofyziologie   MeSH
• mutace genetika   MeSH
• percepce bolesti MeSH
• proteiny nervové tkáně chemie   genetika   metabolismus   MeSH
• vápníkové kanály chemie   genetika   metabolismus   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The structure, expression and function of the transient receptor potential vanilloid 1 (TRPV1) receptor were intensively studied since the cloning in 1997 and TRPV1 receptors are now considered to act as transducers and molecular integrators of nociceptive stimuli in the periphery. In contrast, spinal TRPV1 receptors were studied less extensively and their role in pain modulation is still not fully understood. This short review is a follow up on our previous summary in this area (Spicarova and Palecek 2008). The aim was to review preferentially the most recent findings concerning the role of the spinal TRPV1 receptors, published within the last five years. The update is given on the expression and function of the spinal TRPV1 receptors, their activation by endogenous agonists, interaction between the endocannabinoid and endovanillod system and possible role of the spinal TRPV1 receptors in pathological pain states. There is now mounting evidence that TRPV1 receptors may be an important element in modulation of nociceptive information at the spinal cord level and represent an interesting target for analgesic therapy.

• MeSH
• bolest patofyziologie   MeSH
• endokanabinoidy metabolismus   MeSH
• kationtové kanály TRPV metabolismus   MeSH
• lidé MeSH
• mícha patofyziologie   MeSH
• percepce bolesti * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

• MeSH
• diagnostické techniky neurologické MeSH
• farmakoterapie metody   ošetřování   MeSH
• klinický obraz nemoci MeSH
• komprese míchy diagnóza   komplikace   terapie   MeSH
• lidé MeSH
• mícha * fyziologie   patofyziologie   MeSH
• míšní ischemie diagnóza   komplikace   terapie   MeSH
• myelitida diagnóza   komplikace   terapie   MeSH
• nádory centrálního nervového systému * diagnóza   etiologie   terapie   MeSH
• nádory páteře diagnóza   etiologie   terapie   MeSH
• nemoci míchy * diagnóza   komplikace   terapie   MeSH
• neurochirurgické výkony MeSH
• poranění páteře diagnóza   komplikace   MeSH
• příručky lékařské MeSH
• tromboembolie diagnóza   etiologie   komplikace   MeSH
• Check Tag
• lidé MeSH

• MeSH
• biomechanika MeSH
• komprese míchy diagnóza   komplikace   patofyziologie   MeSH
• lidé MeSH
• lokomoce fyziologie   MeSH
• mícha anatomie a histologie   fyziologie   patofyziologie   MeSH
• motorické neurony fyziologie   MeSH
• paraplegie patofyziologie   MeSH
• poranění míchy * diagnóza   komplikace   patofyziologie   MeSH
• regenerace míchy fyziologie   MeSH
• Check Tag
• lidé MeSH