Bordetella pertussis is the causative agent of whooping cough in humans, a disease that has recently experienced a resurgence. In contrast, Bordetella bronchiseptica infects the respiratory tract of various mammalian species, causing a range of symptoms from asymptomatic chronic carriage to acute illness. Both pathogens utilize type III secretion system (T3SS) to deliver the effector protein BteA into host cells. Once injected, BteA triggers a cascade of events leading to caspase 1-independent necrosis through a mechanism that remains incompletely understood. We demonstrate that BteA-induced cell death is characterized by the fragmentation of the cellular endoplasmic reticulum and mitochondria, the formation of necrotic balloon-like protrusions, and plasma membrane permeabilization. Importantly, genome-wide CRISPR-Cas9 screen targeting 19,050 genes failed to identify any host factors required for BteA cytotoxicity, suggesting that BteA does not require a single nonessential host factor for its cytotoxicity. We further reveal that BteA triggers a rapid and sustained influx of calcium ions, which is associated with organelle fragmentation and plasma membrane permeabilization. The sustained elevation of cytosolic Ca2+ levels results in mitochondrial calcium overload, mitochondrial swelling, cristolysis, and loss of mitochondrial membrane potential. Inhibition of calcium channels with 2-APB delays both the Ca2+ influx and BteA-induced cell death. Our findings indicate that BteA exploits essential host processes and/or redundant pathways to disrupt calcium homeostasis and mitochondrial function, ultimately leading to host cell death.IMPORTANCEThe respiratory pathogens Bordetella pertussis and Bordetella bronchiseptica exhibit cytotoxicity toward a variety of mammalian cells, which depends on the type III secretion effector BteA. Moreover, the increased virulence of B. bronchiseptica is associated with enhanced expression of T3SS and BteA. However, the molecular mechanism underlying BteA cytotoxicity is elusive. In this study, we performed a CRISPR-Cas9 screen, revealing that BteA-induced cell death depends on essential or redundant host processes. Additionally, we demonstrate that BteA disrupts calcium homeostasis, which leads to mitochondrial dysfunction and cell death. These findings contribute to closing the gap in our understanding of the signaling cascades targeted by BteA.
- MeSH
- Bacterial Proteins * metabolism genetics MeSH
- Bordetella bronchiseptica genetics metabolism drug effects MeSH
- Bordetella pertussis genetics pathogenicity metabolism drug effects MeSH
- Cell Death * drug effects MeSH
- Endoplasmic Reticulum metabolism drug effects MeSH
- Homeostasis * MeSH
- Host-Pathogen Interactions MeSH
- Humans MeSH
- Mitochondria metabolism drug effects MeSH
- Type III Secretion Systems metabolism genetics MeSH
- Calcium * metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
beta3-adrenergic activation causes Ca2+ release from the mitochondria and subsequent Ca2+ release from the endoplasmic reticulum (ER), evoking store-operated Ca2+ entry (SOCE) due to Ca2+ depletion from the ER in mouse brown adipocytes. In this study, we investigated how Ca2+ depletion from the ER elicits SOCE in mouse brown adipocytes using fluorometry of intracellular Ca2+ concentration ([Ca2+]i). The administration of cyclopiazonic acid (CPA), a reversible sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) pump blocker in the ER, caused an increase in [Ca2+]i. Moreover, CPA induced SOCE was suppressed by the administration of a Ca2+ free Krebs solution and the transient receptor potential canonical 6 (TRPC6) selective blockers 2-APB, ML-9 and GsMTx-4 but not Pico145, which blocks TRPC1/4/5. Administration of TRPC6 channel agonist 1-oleoyl-2-acetyl-sn-glycerol (OAG) and flufenamic acid elicited Ca2+ entry. Moreover, our RT-PCR analyses detected mRNAs for TRPC6 in brown adipose tissues. In addition, western blot analyses showed the expression of the TRPC6 protein. Thus, TRPC6 is one of the Ca2+ pathways involved in SOCE. These modes of Ca2+ entry provide the basis for heat production via activation of Ca2+-dependent dehydrogenase and the expression of uncoupling protein 1 (UCP1). Enhancing thermogenic metabolism in brown adipocytes may serve as broad therapeutic utility to reduce obesity and metabolic syndrome.
- MeSH
- Endoplasmic Reticulum metabolism MeSH
- Adipocytes, Brown metabolism MeSH
- Transient Receptor Potential Channels * metabolism MeSH
- TRPC Cation Channels metabolism MeSH
- TRPC6 Cation Channel metabolism MeSH
- Mice MeSH
- Calcium metabolism MeSH
- Calcium Signaling MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Úvod: Cílem naší studie u zdravých jedinců bylo posoudit změnu tvaru a délky míchy při dynamickém MR C páteře s míšními funkcemi hodnocenými evokovanými potenciály (EPs). Metodika: Do studie bylo zařazeno pět mužů a pět žen. Vyšetření MR stejně jako EPs (SEPs i MEPs) bylo provedeno v neutrální poloze, předklonu a záklonu. Na MR C páteře byla měřena přední (PD) a zadní délka míchy (ZD), příčný (PR) a předozadní rozměr míchy (PZ) a plocha míchy (P). Byl registrován SEPs n. medianus a n. tibialis, MEPs z mm. BB, APB a TA. Výsledky: Při flexi došlo ke statisticky významnému prodloužení ZD (o 9,2 mm) a PD míchy (o 5,6 mm). Při extenzi pak došlo ke statisticky významnému zkrácení ZD (o 4,3 mm) i PD míchy (o 2 mm). Při extenzi došlo k rozšíření jak PZ, PR i P rozměru míchy. Při flexi došlo ke zvětšení amplitudy míšní komponenty N13. MEPs a SEP n. tibialis byly beze změn. Závěr: Přestože grafické vyšetření prokazuje změnu tvaru a délky míchy v závislosti na změně osy krční páteře, na funkci míchy to u zdravých jedinců nemá zásadní vliv.
Introduction: The aim of our study in healthy individuals was to assess the changes in spinal cord shape and length measured by dynamic C spine MRI with spinal functions assessed by evoked potentials (EPs). Methodology: The study included 5 men and 5 women. MR examination as well as EPs (SEPs and MEPs) were performed in the neutral position, in the flexion and in the extension. The anterior (PD) and posterior spinal cord length (ZD) were measured on the C spine MRI. Then transverse spinal cord dimension (PR), the anteroposterior spinal cord dimension (PZ) and the spinal cord area (P). SEPs n. medianus, SEPs n. tibialis and MEPs were registered. Results: There was a statistically significant increase in ZD (by 9.2 mm) and PD (by 5.6 mm) during flexion. At extension bends, there was a statistically significant shortening of ZD (by 4.3 mm) and PD (by 2 mm). During the extension, the PZ, PR and P dimensions of the spinal cord widened. There was a statistically significant increase in the amplitude of the spinal cord component N13 during flexion for median nerve SEPs. MEPs from lower and upper limbs muscles and tibial nerve SEPs were unchanged. Conclusion: Although the graphical examination shows a change in the shape and length of the spinal cord depending on the change in the axis of the cervical spine, it has no significant effect on the spinal cord function in healthy individuals.
- MeSH
- Axis, Cervical Vertebra anatomy & histology MeSH
- Adult MeSH
- Cervical Vertebrae * anatomy & histology diagnostic imaging MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Spinal Cord * anatomy & histology diagnostic imaging MeSH
- Evoked Potentials, Motor physiology MeSH
- Evoked Potentials, Somatosensory physiology MeSH
- Statistics as Topic MeSH
- Body Constitution MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Clinical Study MeSH
Východiska: Adjuvantní radioterapie (RT) pacientek s časným karcinomem prsu má jako lokální léčba za cíl eliminovat potenciální mikroskopické reziduální onemocnění v operačním poli nebo v jeho blízkém sousedství. Na základě publikovaných studií lze vybraným pacientkám doporučit v této indikaci akcelerované ozáření lůžka tumoru (accelerated partial-breast irradiation – APBI). Cílem této monocentrické prospektivní randomizované studie je porovnat cílenou APBI aplikovanou stereotaktickou technikou s nejčastěji používaným akcelerovaným ozářením celého prsu z hlediska proveditelnosti, bezpečnosti, tolerance a kosmetických efektů. Materiál a metody: Do studie byly zařazeny pacientky s časným karcinomem prsu po parciální mastektomii splňující tato kritéria: věk > 50 let, non-lobulární typ karcinomu, velikost ≤ 2 cm, negativní okraje ≥ 2 mm, L0, ER pozitivní, BRCA negativní. Zařazené pacientky byly randomizovány do dvou ramen podle režimu RT – zevní APBI (5× 6 Gy) nebo akcelerované ozáření celého prsu s boostem na oblast lůžka nádoru (15× 2,67 Gy + 5× 2 Gy). V této práci předkládáme výsledky po prvních 2 letech náboru (zařazeno 57 z 84 plánovaných pacientek). Výsledky: Medián věku pacientek byl 65 let. Karcinom grade 1 byl prokázán u 60 % pacientek, medián velikosti postižení v prsu byl 9 mm a nejčastějším histologickým typem (70 %) byl invazivní karcinom nespecifického typu (NST). Ve všech základních parametrech nebyly mezi skupinami shledány žádné statisticky významné rozdíly. Do APBI skupiny bylo do konce roku 2020 zařazeno celkem 29 pacientek. Jeden měsíc po RT byly zhodnoceny sledované parametry u všech pacientek, ve 3 a 6 měsících po ozáření byly zhodnoceny u 40 (70,2 %) a 33 (58 %) pacientek. Hodnocení toxicity ukázalo statisticky významně méně akutních nežádoucích účinků v APBI skupině ve smyslu kožního erytému, deskvamace, citlivosti kůže, suchosti, otoku, pigmentace, bolesti prsou a únavy. Pozdní toxicita hodnocená za 3 a 6 měsíců po RT byla významně vyšší v kontrolním rameni. Kosmetický efekt (nezávisle hodnocený lékařem, sestrou a pacientem) byl rovněž příznivější pro skupinu s APBI. Závěr: Technika APBI využívající principů cíleného stereotaktického ozáření se ukázala být méně toxickou a snadněji proveditelnou možností pro adjuvantní radioterapii pacientek s časným stadiem karcinomu prsu ve srovnání s ozářením celého prsu s následným boostem. V důsledku toho předložená studie zvyšuje úroveň důkazů pro zavedení tohoto přístupu do každodenní klinické praxe u pacientek splňujících indikační kritéria k APBI.
Background: The adjuvant radiotherapy (RT) of the early-stage breast cancer patients as local treatment aims to eliminate potential microscopic residual disease in the surgery bed or satellites in its neighborhood. Based on published studies, accelerated partial breast irradiation (APBI) is recommended for strictly selected patients. The aim of this single-institution prospective randomized study was to compare the targeted APBI delivered by stereotactic approach with the currently more commonly used accelerated whole breast irradiation with the boost to the tumor bed in terms of feasibility, safety, tolerance, and cosmetic effects. Materials and methods: Early-stage breast cancer patients after partial mastectomy were screened for eligibility. The inclusion criteria were age > 50 years, non-lobular carcinoma histology, size ≤ 2 cm, negative margins ≥ 2 mm, L0, ER-positive, BRCA negative. Enrolled patients were equally randomized into two arms according to radiotherapeutic regiment – external APBI (5× 6 Gy) and accelerated whole breast irradiation with the boost (15× 2,67 Gy + 5× 2 Gy). These preliminary results of the ongoing study evaluated the first 57 from 84 planned patients. Results: The median age was 65 years. The tumors were of grade 1 in 60 % of patients, the median size of 9 mm and 70 % were classified as invasive ductal carcinoma. Statistical significant differences between the groups in baseline characteristics were not observed. A total of 29 patients was enrolled in the APBI group by the end of 2020. All enrolled patients were evaluated one month after RT. A total of 40 (70,2 %) a 33 (58 %) had examinations 3 and 6 months after RT, respectively. Toxicity evaluation showed statistically significantly fewer acute adverse events in the APBI group in terms of skin erythema, desquamation, skin tenderness, dryness, edema, pigmentation, breast pain and fatigue. Late toxicity evaluated in 3 and 6 months after RT was significantly higher in the control group. The cosmetic effect (independently evaluated by a physician, nurse and patient) was more favorable to the APBI group. Conclusion: The technique using the principles of targeted radiotherapy turned out to be a less toxic and easier feasible approach for adjuvant radiation of early-stage breast cancer patients. Consequently, the presented study increases the level of evidence for RT-indicated patients to the establishment of external APBI into daily clinical practice.
Background: The pathogenesis of adolescent idiopathic scoliosis (AIS), including the role of brain and spinal inhibitory circuits, is still poorly elucidated. The aim of this study was to identify which central inhibitory mechanisms are involved in the pathogenesis of AIS.Design: A prospective neurophysiological study, using a battery of neurophysiological tests, such as cutaneous (CuSP) and cortical (CoSP) silent periods, motor evoked potentials (MEP) and paired-pulse transcranial magnetic stimulation (ppTMS).Settings: Neurophysiological laboratory.Participants: Sixteen patients with AIS (14 females, median age 14.4) and healthy controls.Outcome measures: MEPs were obtained after transcranial magnetic stimulation (TMS) and recorded from the abductor pollicis muscle (APB). ppTMS was obtained at interval ratios (ISI) of 1, 2, 3, 6, 10, 15 and 20 ms. The cortical silent period (CoSP) was recorded from the APB. The cutaneous silent period (CuSP) was measured after painful stimuli delivered to the thumb while the subjects maintained voluntary contraction of the intrinsic hand muscles. The data were analyzed and compared with those from healthy subjects.Results: The CoSP duration was significantly prolonged in AIS patients. A significantly higher amplitude of ppTMS for ISI was found in all AIS patients, without remarkable left-right side differences. No significant difference in MEP latency or amplitude nor in the CuSP duration was obtained.Conclusion: Our observation demonstrates evidence of central nervous system involvement in adolescent idiopathic scoliosis (AIS). Lower intracortical inhibition, higher motor cortex excitability, and preserved spinal inhibitory circuits are the main findings of this study. A possible explanation of these changes could be attributed to impaired sensorimotor integration predominantly at the cortical level.
- MeSH
- Electric Stimulation MeSH
- Electromyography MeSH
- Muscle, Skeletal physiology MeSH
- Humans MeSH
- Adolescent MeSH
- Evoked Potentials, Motor physiology MeSH
- Motor Cortex * physiology MeSH
- Spinal Cord Injuries * MeSH
- Prospective Studies MeSH
- Scoliosis * MeSH
- Transcranial Magnetic Stimulation MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The lipid molecule, lysophosphatidylinositol (LPI), is hypothesised to form part of a novel lipid signalling system that involves the G protein-coupled receptor GPR55 and distinct intracellular signalling cascades in endothelial cells. This work aimed to study the possible mechanisms involved in LPI-evoked cytosolic Ca(2+) mobilization in human brain microvascular endothelial cells. Changes in intracellular Ca(2+) concentrations were measured using cell population Ca(2+) assay. LPI evoked biphasic elevation of intracellular calcium concentration, a rapid phase and a sustained phase. The rapid phase was attenuated by the inhibitor of PLC (U 73122), inhibitor of IP(3) receptors, 2-APB and the depletor of endoplasmic reticulum Ca(2+) store, thapsigargin. The sustained phase, on the other hand, was enhanced by U 73122 and abolished by the RhoA kinase inhibitor, Y-27632. In conclusion, the Ca(2+) signal evoked by LPI is characterised by a rapid phase of Ca(2+) release from the endoplasmic reticulum, and requires activation of the PLC-IP(3) signalling pathway. The sustained phase mainly depends on RhoA kinase activation. LPI acts as novel lipid signalling molecule in endothelial cells, and elevation of cytosolic Ca(2+) triggered by it may present an important intracellular message required in gene expression and controlling of vascular tone.
- MeSH
- Cytosol drug effects metabolism MeSH
- Endothelial Cells drug effects metabolism MeSH
- Humans MeSH
- Lysophospholipids pharmacology MeSH
- Microvessels drug effects metabolism MeSH
- Cell Line, Transformed MeSH
- Calcium Signaling drug effects physiology MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Transient receptor potential (TRP) channels are proposed to contribute to membrane depolarization and Ca2+ influx into vascular smooth muscle (VSM) cells. Our aim was to study the effects of widely used broad-range TRP channel inhibitors--2-aminoethoxydiphenyl borate (2-APB), flufenamic acid (FFA) and SKF-96365--on the contraction of freshly isolated small and large arteries. Endothelium-denuded resistance (≈250 μm) and conduit (≈1000 μm) femoral arteries were isolated from adult Wistar rats and mounted in wire myograph. The effects of the above mentioned TRP channel inhibitors and voltage-dependent calcium channel inhibitor nifedipine were studied on arterial contractions induced by phenylephrine, U-46619 or K+. Phenylephrine-induced contractions were also studied in the absence of extracellular Na+. mRNA expression of particular canonical and melastatin TRP channel subunits in femoral vascular bed was determined. TRP channel inhibitors attenuated K+-induced contraction less than nifedipine. Phenylephrine-induced contraction was more influenced by 2-APB in resistance arteries, while FFA completely prevented U-46619-induced contraction in both sizes of arteries. The absence of extracellular Na+ prevented the inhibitory effects of 2-APB, but not those of FFA. The observed effects of broad-range TRP channel inhibitors, which were dependent on the size of the artery, confirmed the involvement of TRP channels in agonist-induced contractions. The inhibitory effects of 2-APB (but not those of FFA or SKF-96365) were dependent on the presence of extracellular Na+.
- MeSH
- Femoral Artery drug effects physiology MeSH
- Imidazoles pharmacology MeSH
- Transient Receptor Potential Channels antagonists & inhibitors physiology MeSH
- Rats MeSH
- Flufenamic Acid pharmacology MeSH
- Organ Culture Techniques MeSH
- Rats, Wistar MeSH
- Boron Compounds pharmacology MeSH
- Muscle, Smooth, Vascular drug effects physiology MeSH
- Vasoconstriction drug effects physiology MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Úvod: Problematika vzťahu hemisferálnej dominancie horných končatín a rečových funkcií v zdravej populácii je stále predmetom skúmania a diskusie. Použili sme fokálnu transkraniálnu magnetickú stimuláciu (TMS) ako neinvazívnu vyšetrovaciu metódu k stanoveniu hemisferálnej dominancie končatín a reči a výsledky sme porovnali s viacerými neuropsychologickými testami. Metodika: 91 zdravých osôb (vek 26 ? 4,6) podstúpilo neuropsychologické testovanie končatinovej dominancie, mapovanie kortikálnej reprezentácie m. abductor pollicis brevis (APB) fokálnou TMS a repetitívnu TMS (rTMS) k stanoveniu lateralizácie rečových funkcií – rTMS(1) s paradigmou číselného radu a rTMS(2) s paradigmou generovania slov. Výsledky: Zistili sme štatisticky významnú koreláciu medzi kortikálnou asymetriou reprezentácie ľavého a pravého APB a všetkými neuropsychologickými testami končatinovej dominancie (p < 0,001). Lateralizácia zástavy reči zistená rTMS(1) korelovala s rozhodujúcou väčšinou testov končatinovej dominancie. Pri rTMS(2) sme zistili významne dlhší reakčný čas v 29 zo 42 testovaných subjektoch, ale zistili sme pozitívnu koreláciu s jedným z testov. Závery: Končatinová dominancia je združená s asymetriou kortikálnej reprezentácie APB. Pravostranná dominancia reči v skupine zdravých pravákov nie je taká zriedkavá, ako sa myslí (9,5 %). Čím je výraznejšia ľavorukosť, tým vyššia je pravdepodobnosť lateralizácie rečových funkcií v pravej hemisfére (9,5–33 %). Použitím rTMS sme ďalej zistili: a) tvorba reči môže byť ovplyvnená v dvoch rôznych miestach gyrus frontalis inferior, b) pars triangularis je zavzatá do verbálnej produkcie iba u niektorých jedincov, c) motorický prah je významne vyšší pre kognitívne ako pre motorické funkcie. TMS s použitím fokálnej cievky môže byť objektívnou metódou k určeniu končatinovej a rečovej hemisferálnej dominancie.
Introduction: There still is some debate about the relationship between handedness and speech in healthy subjects. We used focal transcranial magnetic stimulation (TMS) as a non‑invasive method to determine hemispheric dominance and compared our results with several neuropsychological tests. Methods: 91 healthy subjects (age 26 ? 4.6) underwent neuropsychological testing for handedness, TMS mapping of cortical representation of abductor pollicis brevis (APB), repetitive TMS (rTMS) to determine language lateralization with Number‑counting paradigm – rTMS(1), and Verb‑generation paradigm – rTMS(2). Results: There was a significant correlation between cortical asymmetry of the left/ right APB and all the used neuropsychological tests of handedness (p < 0.001). Laterality of speech arrest using rTMS(1) correlated with the majority of tests for handedness. When rTMS(2) was used, there was significantly longer reaction time in 29/42 subjects but we found correlation with only one of the tests. Conclusion: Handedness is associated with asymmetry in cortical motor representation. Right‑cerebral dominance for language in healthy right‑handers is not as rare as it was supposed (9.5%). Stronger left‑handedness is associated with higher probability of language dominance in the right hemisphere (9.5–33%). When using rTMS, we found that: a) speech production can be influenced by 2 different areas in the gyrus frontalis inferior, b) pars triangularis is involved in verb production only in some subjects, c) motor threshold is significantly higher for cognitive processes than for motor functions. TMS with focal magnetic coil can be used as an objective method for mapping cortical motor asymmetry of handedness and language functions.
- MeSH
- Dominance, Cerebral MeSH
- Adult MeSH
- Electroencephalography MeSH
- Functional Laterality * physiology MeSH
- Upper Extremity * MeSH
- Humans MeSH
- Young Adult MeSH
- Evoked Potentials, Motor MeSH
- Brain physiology MeSH
- Neuropsychology MeSH
- Speech * MeSH
- Statistics as Topic MeSH
- Transcranial Magnetic Stimulation * MeSH
- Cerebrum MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
All secretory anterior pituitary cells fire action potentials spontaneously and exhibit a high resting cation conductance, but the channels involved in the background permeability have not been identified. In cultured lactotrophs and immortalized GH(3) cells, replacement of extracellular Na(+) with large organic cations, but not blockade of voltage-gated Na(+) influx, led to an instantaneous hyperpolarization of cell membranes that was associated with a cessation of spontaneous firing. When cells were clamped at -50 mV, which was close to the resting membrane potential in these cells, replacement of bath Na(+) with organic cations resulted in an outward-like current, reflecting an inhibition of the inward holding membrane current and indicating loss of a background-depolarizing conductance. Quantitative RT-PCR analysis revealed the high expression of mRNA transcripts for TRPC1 and much lower expression of TRPC6 in both lactotrophs and GH(3) cells. Very low expression of TRPC3, TRPC4, and TRPC5 mRNA transcripts were also present in pituitary but not GH(3) cells. 2-APB and SKF-96365, relatively selective blockers of TRPC channels, inhibited electrical activity, Ca(2+) influx and prolactin release in a concentration-dependent manner. Gd(3+), a common Ca(2+) channel blocker, and flufenamic acid, an inhibitor of non-selective cation channels, also inhibited electrical activity, Ca(2+) influx and prolactin release. These results indicate that nonselective cation channels, presumably belonging to the TRPC family, contribute to the background depolarizing conductance and firing of action potentials with consequent contribution to Ca(2+) influx and hormone release in lactotrophs and GH(3) cells.
- MeSH
- Action Potentials MeSH
- Time Factors MeSH
- Ion Channels genetics metabolism drug effects MeSH
- TRPC Cation Channels genetics metabolism drug effects MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Real-Time Polymerase Chain Reaction MeSH
- Lactotrophs metabolism secretion drug effects MeSH
- RNA, Messenger metabolism MeSH
- Patch-Clamp Techniques MeSH
- Membrane Transport Modulators pharmacology MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Rats, Sprague-Dawley MeSH
- Prolactin secretion MeSH
- Sodium metabolism MeSH
- Calcium metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Intramural MeSH
OBJECTIVES AND METHODS: Excitability changes in the primary motor cortex in 17 spinal-cord injured (SCI) patients and 10 controls were studied with paired-pulse transcranial magnetic stimulation. The paired pulses were applied at inter-stimulus intervals (ISI) of 2 ms and 15 ms while motor evoked potentials (MEP) were recorded in the biceps brachii (Bic), the abductor pollicis brevis (APB) and the tibialis anterior (TA) muscles. RESULTS: The study revealed a significant decrease in cortical motor excitability in the first weeks after SCI concerning the representation of both the affected muscles innervated from spinal segments below the lesion, and the spared muscles rostral to the lesion. In the patients with motor-incomplete injury, but not in those with motor-complete injury, the initial cortical inhibition of affected muscles was temporarily reduced 2-3 months following injury. The degree of inhibition in cortical areas representing the spared muscles was observed to be smaller in patients with no voluntary TA activity compared to patients with some activity remaining in the TA. Surprisingly, motor-cortical inhibition was observed not only at ISI 2 ms but also at ISI 15 ms. The inhibition persisted in patients who returned for a follow-up measurement 2-3 years later. CONCLUSION: The present data showed different evaluation of cortical excitability between patients with complete and incomplete spinal cord lesion. Our results provide more insight into the pathophysiology of SCI and contribute to the ongoing discussion about the recovery process and therapy of SCI patients.
- MeSH
- Analysis of Variance MeSH
- Time Factors MeSH
- Adult MeSH
- Efferent Pathways physiology physiopathology MeSH
- Muscle, Skeletal innervation physiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Evoked Potentials, Motor physiology MeSH
- Motor Cortex physiology MeSH
- Neural Inhibition physiology MeSH
- Neurons, Efferent physiology MeSH
- Spinal Cord Injuries physiopathology MeSH
- Reference Values MeSH
- Case-Control Studies MeSH
- Transcranial Magnetic Stimulation MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
