Excitatory action of low frequency depolarizing GABA/glycine synaptic inputs is prevalent in prenatal spinal SOD1G93A motoneurons.

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease characterized by progressive motor neuron degeneration and muscle paralysis. Recent evidence suggests the dysfunction of inhibitory signalling in ALS motor neurons. We have shown that embryonic day (E)17.5 spinal motoneurons (MNs) of the SOD1G93A mouse model of ALS exhibit an altered chloride homeostasis. At this prenatal stage, inhibition of spinal motoneurons (MNs) is mediated by depolarizing GABAergic/glycinergic postsynaptic potentials (dGPSPs). Here, using an ex vivo preparation and patch clamp recording from MNs with a chloride equilibrium set below spike threshold, we report that low input resistance (Rin ) E17.5 MNs from the SOD1G93A ALS mouse model do not correctly integrate dGPSPs evoked by electrical stimulations of GABA/glycine inputs at different frequencies. Indeed, firing activity of most wild-type (WT) MNs with low Rin was inhibited by incoming dGPSPs, whereas low Rin SOD1G93A MNs were excited or exhibited a dual response (excited by low frequency dGPSPs and inhibited by high frequency dGPSPs). Simulation highlighted the importance of the GABA/glycine input density and showed that pure excitation could be obtained in SOD-like MNs by moving GABA/glycine input away from the cell body to dendrites. This was in agreement with confocal imaging showing a lack of peri-somatic inhibitory terminals in SOD1G93A MNs compared to WT littermates. Putative fast ALS-vulnerable MNs with low Rin are therefore lacking functional inhibition at the near-term prenatal stage. KEY POINTS: We analysed the integration of GABAergic/glycinergic synaptic events by embryonic spinal motoneurons (MNs) in a mouse model of the amyotrophic lateral sclerosis (ALS) neurodegenerative disease. We found that GABAergic/glycinergic synaptic events do not properly inhibit ALS MNs with low input resistance, most probably corresponding to future vulnerable MNs. We used a neuron model to highlight the importance of the GABA/glycine terminal location and density in the integration of the GABAergic/glycinergic synaptic events. Confocal imaging showed a lack of GABA/glycine terminals on the cell body of ALS MNs. The present study suggests that putative ALS vulnerable MNs with low Rin lack functional inhibition at the near-term stage.

Acute Type B Aortic Dissection: Insights From a Single-Center Retrospective Experience Over 12 Years.

INTRODUCTION: The treatment of acute type B aortic dissection (ATBAD) is currently a challenge for vascular surgeons, because of the early morbidity and mortality rates and the high risk of late aortic events up to 50% at 5 years. This study presents the initial outcomes of ATBAD treatment using optimal medical therapy alone or combined with proximal entry tear stent-graft coverage. Additionally, it provides an analysis of the evolution of the aortic diameter and its clinical consequences during the chronic phase in each group. MATERIALS AND METHODS: Conducted as a retrospective, single-center study, we enrolled all consecutive ATBAD patients (n=130) treated between 2008 and 2020. The primary analysis studies the entire patient cohort based on their initial management approach, namely, medical treatment alone for uncomplicated ATBAD (n=67) or combined with stent-graft entry tear coverage (n=63). We also conducted a subgroup analysis to investigate factors associated with disease progression in the medical management group. RESULTS: Median follow-up was 29.5 months. During this time aneurysmal evolution was observed in: 42.4% of cases in the medical group compared with 21.8% in the stent-graft group, primarily affecting the thoracic aorta. The stent-graft group exhibited significant aortic remodeling, with a decrease in false lumen (FL) and thoracic aortic diameters. Initial aortic diameter ≥40 mm and FL ≥22 mm were independent risk factors for aneurysmal degeneration. Five-year survival was consistent at 76.1% in both groups. CONCLUSION: This study confirms the safety and efficacy of stent-graft entry tear coverage for ATBAD. Initial thoracic endovascular aortic repair (TEVAR) appears to reduce late aortic events by promoting aortic remodeling. Considering TEVAR's safety and potential to prevent late aortic complications, it may be considered for uncomplicated ATBAD patients with an initial aortic diameter ≥40 mm or an FL ≥22 mm. CLINICAL IMPACT: This study validates the efficacy and safety of using endovascular stent grafts to seal the proximal entry tear in cases of acute type B aortic dissections, compared to optimal medical therapy. Aortic remodelling significantly benefits from endovascular stent graft coverage of the proximal entry tear. Given the heightened risk of late aortic events observed in the medical therapy cohort, there appears to be a necessity for including endovascular interventions in the management of uncomplicated acute type B aortic dissections, particularly when aortic diameter is ≥40 mm and false lumen diameter is ≥22 mm.

Outcomes of Cold Stored Saphenous Vein Allografts for Haemodialysis Vascular Access.

OBJECTIVE: The aim of this study was to evaluate the outcomes of cold stored saphenous vein allografts (CSVAs) for haemodialysis vascular access. METHODS: A retrospective, two centre study was conducted between January 2016 and December 2020 of all patients who had CSVA placement for haemodialysis vascular access. Primary, primary assisted, and secondary patency were analysed, as well as procedural complications and re-interventions. RESULTS: One hundred and nine patients (n = 55 women) with a mean age of 67.2 ± 13.6 years, with no options for creating an autogenous arteriovenous fistula, were included in the study. At one year, primary, primary assisted, and secondary patency were 37.6%, 59.0%, and 73.3%, respectively; and at two years 19.9%, 42.5%, and 54.9%, respectively. During a mean follow up period of 26 ± 18 months, five patients (4.6%) had an access infection, with no related death. During the follow up period, 32 patients (29.4%) died and 13 patients (11.9%) underwent a kidney transplant. None of these patients showed immunoconversion before transplantation. The cumulative incidence of adverse events by the Fine-Gray method was calculated. Considering competing risks (death and renal transplantation), 9.2% of patients lost their vascular access at one year and 18% at two years. Moreover, 57.8% patients had stenosis, mainly on the outflow (45.9%), and 49.5% had thrombosis. CONCLUSION: With a comparable patency rate associated with a low infection rate, CSVA offers a potential alternative to expanded polytetrafluoroethylene grafts. This creates haemodialysis vascular access when the venous capital is exhausted in patients with reported risk factors for vascular access infection, i.e., insertion in the thigh, advanced age, diabetes mellitus, immunocompromised state, obesity, or revision of an infected prosthetic graft.

Elective late open conversion after endovascular aneurysm repair is associated with comparable outcomes to primary open repair of abdominal aortic aneurysms.

OBJECTIVE: Three of four patients with infrarenal abdominal aortic aneurysm are now treated with endovascular aneurysm repair (EVAR). The incidence of secondary procedures and surgical conversions is increasing for a population theoretically unfit for open surgery. The indications and outcomes of late open surgical conversions after EVAR in a high-volume tertiary vascular unit are reported. METHODS: This retrospective single-center study includes all patients who underwent a late open conversion between January 1996 and July 2018. Data were collected from records on patient demographics, operative indications, surgical strategy, perioperative outcomes, and medium-term survival. RESULTS: Sixty-two consecutive patients (88.7% male) with a mean age of 77.5 years are included. The median duration since index EVAR was 38.5 months; 65% of stent grafts requiring late open conversion had suprarenal fixation. Indications included 22.6% type IA, 16.1% type IB, and 45.2% type II endoleaks; 12.9% graft thrombosis; and 14.5% endoprosthesis infection. Complete endograft explantation was performed in 37.1% of patients and a partial explantation in 54.8%, whereas 8.1% of stent grafts were wholly preserved in situ. Overall 30-day mortality was 12.9% (n = 8) in the cohort and 2.7% for elective patients. The all-cause morbidity rate was 40.1%, and the median length of hospital stay was 9 days. After follow-up of 28.4 months (range, 1.8-187.3 months), all-cause survival was 58.8%. Avoidance of aortic clamping (P = .006) and elective procedures (P = .019) were associated with a significant reduction in the length of hospital stay. Moreover, the 30-day mortality (P = .002), occurrence of postoperative renal dysfunction (P = .004), and intestinal ischemia (P = .017) were increased in the emergency setting. Excluding cases with rupture or infection, survival estimates were 97%, 97%, and 71% at 1 year, 2 years, and 5 years, respectively. CONCLUSIONS: Technically more complex than primary open surgery, late open conversion is a procedure that generates an acceptable perioperative risk when it is performed in a high-volume aortic surgical center. Elective open conversion is associated with excellent early and late outcomes. Endograft preservation strategies decrease perioperative morbidity.

Implication of 5-HT in the Dysregulation of Chloride Homeostasis in Prenatal Spinal Motoneurons from the G93A Mouse Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration and muscle paralysis. The early presymptomatic onset of abnormal processes is indicative of cumulative defects that ultimately lead to a late manifestation of clinical symptoms. It remains of paramount importance to identify the primary defects that underlie this condition and to determine how these deficits lead to a cycle of deterioration. We recently demonstrated that prenatal E17.5 lumbar spinal motoneurons (MNs) from SOD1G93A mice exhibit a KCC2-related alteration in chloride homeostasis, i.e., the EGABAAR is more depolarized than in WT littermates. Here, using immunohistochemistry, we found that the SOD1G93A lumbar spinal cord is less enriched with 5-HT descending fibres than the WT lumbar spinal cord. High-performance liquid chromatography confirmed the lower level of the monoamine 5-HT in the SOD1G93A spinal cord compared to the WT spinal cord. Using ex vivo perforated patch-clamp recordings of lumbar MNs coupled with pharmacology, we demonstrated that 5-HT strongly hyperpolarizes the EGABAAR by interacting with KCC2. Therefore, the deregulation of the interplay between 5-HT and KCC2 may explain the alteration in chloride homeostasis detected in prenatal SOD1G93A MNs. In conclusion, 5-HT and KCC2 are two likely key factors in the presymptomatic phase of ALS, particular in familial ALS involving the SOD1G93A mutation.

Persistent Sodium Current Drives Excitability of Immature Renshaw Cells in Early Embryonic Spinal Networks.

Spontaneous network activity (SNA) emerges in the spinal cord (SC) before the formation of peripheral sensory inputs and central descending inputs. SNA is characterized by recurrent giant depolarizing potentials (GDPs). Because GDPs in motoneurons (MNs) are mainly evoked by prolonged release of GABA, they likely necessitate sustained firing of interneurons. To address this issue we analyzed, as a model, embryonic Renshaw cell (V1R) activity at the onset of SNA (E12.5) in the embryonic mouse SC (both sexes). V1R are one of the interneurons known to contact MNs, which are generated early in the embryonic SC. Here, we show that V1R already produce GABA in E12.5 embryo, and that V1R make synaptic-like contacts with MNs and have putative extrasynaptic release sites, while paracrine release of GABA occurs at this developmental stage. In addition, we discovered that V1R are spontaneously active during SNA and can already generate several intrinsic activity patterns including repetitive-spiking and sodium-dependent plateau potential that rely on the presence of persistent sodium currents (INap). This is the first demonstration that INap is present in the embryonic SC and that this current can control intrinsic activation properties of newborn interneurons in the SC of mammalian embryos. Finally, we found that 5 µm riluzole, which is known to block INaP, altered SNA by reducing episode duration and increasing inter-episode interval. Because SNA is essential for neuronal maturation, axon pathfinding, and synaptogenesis, the presence of INaP in embryonic SC neurons may play a role in the early development of mammalian locomotor networks.SIGNIFICANCE STATEMENT The developing spinal cord (SC) exhibits spontaneous network activity (SNA) involved in the building of nascent locomotor circuits in the embryo. Many studies suggest that SNA depends on the rhythmic release of GABA, yet intracellular recordings of GABAergic neurons have never been performed at the onset of SNA in the SC. We first discovered that embryonic Renshaw cells (V1R) are GABAergic at E12.5 and spontaneously active during SNA. We uncover a new role for persistent sodium currents (INaP) in driving plateau potential in V1R and in SNA patterning in the embryonic SC. Our study thus sheds light on a role for INaP in the excitability of V1R and the developing SC.

Acetylcholine controls GABA-, glutamate-, and glycine-dependent giant depolarizing potentials that govern spontaneous motoneuron activity at the onset of synaptogenesis in the mouse embryonic spinal cord.

A remarkable feature of early neuronal networks is their endogenous ability to generate spontaneous rhythmic electrical activity independently of any external stimuli. In the mouse embryonic SC, this activity starts at an embryonic age of ∼ 12 d and is characterized by bursts of action potentials recurring every 2-3 min. Although these bursts have been extensively studied using extracellular recordings and are known to play an important role in motoneuron (MN) maturation, the mechanisms driving MN activity at the onset of synaptogenesis are still poorly understood. Because only cholinergic antagonists are known to abolish early spontaneous activity, it has long been assumed that spinal cord (SC) activity relies on a core network of MNs synchronized via direct cholinergic collaterals. Using a combination of whole-cell patch-clamp recordings and extracellular recordings in E12.5 isolated mouse SC preparations, we found that spontaneous MN activity is driven by recurrent giant depolarizing potentials. Our analysis reveals that these giant depolarizing potentials are mediated by the activation of GABA, glutamate, and glycine receptors. We did not detect direct nAChR activation evoked by ACh application on MNs, indicating that cholinergic inputs between MNs are not functional at this age. However, we obtained evidence that the cholinergic dependency of early SC activity reflects a presynaptic facilitation of GABA and glutamate synaptic release via nicotinic AChRs. Our study demonstrates that, even in its earliest form, the activity of spinal MNs relies on a refined poly-synaptic network and involves a tight presynaptic cholinergic regulation of both GABAergic and glutamatergic inputs.

Outcomes of cold-stored venous allograft for below-knee bypasses in patients with critical limb ischemia.

OBJECTIVE: Critical limb ischemia (CLI), the most advanced form of peripheral arterial disease, is associated with strikingly high morbidity and mortality rates. Autogenous single-segment great saphenous vein (GSV) remains the optimal conduit for infrainguinal revascularization. Unfortunately, GSV is unavailable in up to 20% of patients. There is no consensus about the alternative graft that should be used for infragenicular bypass grafting when the GSV is unavailable. Currently, there are no outcome data for cold-stored venous allograft use in regard to recent safety and efficacy objective performance goals described by the Society for Vascular Surgery. METHODS: This is a retrospective analysis of 118 infragenicular revascularizations performed for CLI with cold-stored venous allografts obtained from varicose vein stripping surgery in a single institution from November 2002 to August 2013. RESULTS: Mean age (± standard deviation) was 75 ± 12 years (male, 76%; diabetes, 73%; dialysis, 16%), and 38% (n = 45) had a history of failed ipsilateral revascularization. None had suitable autogenous conduit for even composite vein bypass. The distal anastomosis was performed to an infrapopliteal artery in 85 cases (72%). At 30 days, perioperative death rate was 6.8%, major adverse cardiovascular event rate was 7.6%, and major adverse limb event rate was 11.9%. Mean follow-up was 34 ± 29 months (range, 1-113 months). At 1 year, freedom from major adverse limb event or perioperative death, limb salvage, survival, amputation-free survival, and secondary patency rates were, respectively, 64.9%, 82.5%, 85.4%, 73.3%, and 58.3%. Ejection fraction <45% and dialysis were the most significant factors predicting failure of revascularization. CONCLUSIONS: Cold-stored venous allografts may be used for performing infragenicular revascularization for CLI with acceptable safety and efficacy results despite poor long-term patency. Their level of performance remains inferior to autologous vein sources but seems comparable to alternative allografts or prosthetic conduit. Their availability is a major advantage compared with other biologic alternative sources.

BiœmuS: A new tool for neurological disorders studies through real-time emulation and hybridization using biomimetic Spiking Neural Network.

Characterization and modeling of biological neural networks has emerged as a field driving significant advancements in our understanding of brain function and related pathologies. As of today, pharmacological treatments for neurological disorders remain limited, pushing the exploration of promising alternative approaches such as electroceutics. Recent research in bioelectronics and neuromorphic engineering have fostered the development of the new generation of neuroprostheses for brain repair. However, achieving their full potential necessitates a deeper understanding of biohybrid interaction. In this study, we present a novel real-time, biomimetic, cost-effective and user-friendly neural network capable of real-time emulation for biohybrid experiments. Our system facilitates the investigation and replication of biophysically detailed neural network dynamics while prioritizing cost-efficiency, flexibility and ease of use. We showcase the feasibility of conducting biohybrid experiments using standard biophysical interfaces and a variety of biological cells as well as real-time emulation of diverse network configurations. We envision our system as a crucial step towards the development of neuromorphic-based neuroprostheses for bioelectrical therapeutics, enabling seamless communication with biological networks on a comparable timescale. Its embedded real-time functionality enhances practicality and accessibility, amplifying its potential for real-world applications in biohybrid experiments.

Embryonic alteration of motoneuronal morphology induces hyperexcitability in the mouse model of amyotrophic lateral sclerosis.

Although amyotrophic lateral sclerosis (ALS) is an age-dependent fatal neurodegenerative disease in which upper and lower motoneurons (MNs) are targeted for death in adults, increasing lines of evidence indicate that MNs display physiological and morphological abnormalities during postnatal development, long before disease onset. Here, using transgenic mice overexpressing the G93A mutation of the human Cu/Zn superoxide dismutase gene (SOD1), we show that SOD1(G93A) embryonic lumbar E17.5 MNs already expressed abnormal morphometric parameters, including a deep reduction of their terminal segments length. Whole-cell patch-clamp recordings from acute spinal cord preparations were made to characterize functional changes in neuronal activity. SOD1(G93A) E17.5 MNs displayed hyperexcitability compared to wild-type MNs. Finally, we performed realistic simulations in order to correlate morphometric and electrophysiological changes observed in embryonic SOD1(G93A) MNs. We found that the reduced dendritic elongation mainly accounted for the hyperexcitability observed in SOD1(G93A) MNs. Altogether, our results emphasize the remarkable early onset of abnormal neural activity in the commonly used animal model for ALS, and suggest that embryonic morphological changes are the primary compensatory mechanisms, the physiological adjustments being only secondary to morphological alterations.

Improvement in conformability of the latest generation of thoracic stent grafts.

OBJECTIVE: Poor aortic arch apposition increases the risk of technical failure after thoracic endovascular repair. The aim of this study was to assess the conformability of the latest generation of thoracic stent grafts in relation to the degree of device oversizing and aortic arch angulation. METHODS: A benchtop pulsatile flow model was designed to test stent graft anchorage in a 2-cm-long proximal landing zone at varying landing zone angles (from 140° down to 70°) and stent graft oversizing (12%-28%). The experiments were performed using 10 human thoracic cadaveric aortas and four stent grafts: C-TAG, Zenith TX2 Pro-Form, Valiant Captivia, and Relay. Device-wall apposition was measured as a function of landing zone angulation and oversizing during static and dynamic (60 pulses/min, 300/150 mm Hg) tests. RESULTS: The Valiant stent graft remained apposed to the aortic wall at each increment of neck angulation and device oversizing. Lack of apposition of the proximal anchorage segment was observed with the C-TAG above 120° landing zone angulation (1-2 mm) and with the Relay above 110° landing zone angulation (1-4 mm). Lack of "body" apposition (1-4 mm) was first observed with the Zenith Pro-Form stent graft above 110° angulation (P = .001). When the device was not apposed to the aortic wall, an increase in stent graft oversizing significantly (P = .01) decreased device-wall apposition. CONCLUSIONS: The requirement for close conformability has influenced the design of next-generation devices. Manufacturers have modified devices and/or their deployment system to specifically address this problem. When compared with the results of our previous experimental test, this study demonstrates that these alterations have resulted in a marked improvement in the performance of commercially available stent graft systems.

Chloride Homeostasis in Developing Motoneurons.

Maturation of GABA/Glycine chloride-mediated synaptic inhibitions is crucial for the establishment of a balance between excitation and inhibition. GABA and glycine are excitatory neurotransmitters on immature neurons that exhibit elevated [Cl-]i. Later in development [Cl-]i drops leading to the occurrence of inhibitory synaptic activity. This ontogenic change is closely correlated to a differential expression of two cation-chloride cotransporters that are the Cl- channel K+/Cl- co-transporter type 2 (KCC2) that extrudes Cl- ions and the Na+-K+-2Cl- cotransporter NKCC1 that accumulates Cl- ions. The classical scheme built from studies performed on cortical and hippocampal networks proposes that immature neurons display high [Cl-]i because NKCC1 is overexpressed compared to KCC2 and that the co-transporters ratio reverses in mature neurons, lowering [Cl-]i. In this chapter, we will see that this classical scheme is not true in motoneurons (MNs) and that an early alteration of the chloride homeostasis may be involved in pathological conditions.

From real-time single to multicompartmental Hodgkin-Huxley neurons on FPGA for bio-hybrid systems.

Modeling biological neural networks has been a field opening to major advances in our understanding of the mechanisms governing the functioning of the brain in normal and pathological conditions. The emergence of real-time neuromorphic platforms has been leading to a rising significance of bio-hybrid experiments as part of the development of neuromorphic biomedical devices such as neuroprosthesis. To provide a new tool for the neurological disorder characterization, we design real-time single and multicompartmental Hodgkin-Huxley neurons on FPGA. These neurons allow biological neural network emulation featuring improved accuracy through compartment modeling and show integration in bio-hybrid system thanks to its real-time dynamics.

Glycine release from radial cells modulates the spontaneous activity and its propagation during early spinal cord development.

Rhythmic electrical activity is a hallmark of the developing embryonic CNS and is required for proper development in addition to genetic programs. Neurotransmitter release contributes to the genesis of this activity. In the mouse spinal cord, this rhythmic activity occurs after embryonic day 11.5 (E11.5) as waves spreading along the entire cord. At E12.5, blocking glycine receptors alters the propagation of the rhythmic activity, but the cellular source of the glycine receptor agonist, the release mechanisms, and its function remain obscure. At this early stage, the presence of synaptic activity even remains unexplored. Using isolated embryonic spinal cord preparations and whole-cell patch-clamp recordings of identified motoneurons, we find that the first synaptic activity develops at E12.5 and is mainly GABAergic. Using a multiple approach including direct measurement of neurotransmitter release (i.e., outside-out sniffer technique), we also show that, between E12.5 and E14.5, the main source of glycine in the embryonic spinal cord is radial cell progenitors, also known to be involved in neuronal migration. We then demonstrate that radial cells can release glycine during synaptogenesis. This spontaneous non-neuronal glycine release can also be evoked by mechanical stimuli and occurs through volume-sensitive chloride channels. Finally, we find that basal glycine release upregulates the propagating spontaneous rhythmic activity by depolarizing immature neurons and by increasing membrane potential fluctuations. Our data raise the question of a new role of radial cells as secretory cells involved in the modulation of the spontaneous electrical activity of embryonic neuronal networks.

Maturation of the GABAergic transmission in normal and pathologic motoneurons.

γ-aminobutyric acid (GABA) acting on Cl(-)-permeable ionotropic type A (GABA(A)) receptors (GABA(A)R) is the major inhibitory neurotransmitter in the adult central nervous system of vertebrates. In immature brain structures, GABA exerts depolarizing effects mostly contributing to the expression of spontaneous activities that are instructive for the construction of neural networks but GABA also acts as a potent trophic factor. In the present paper, we concentrate on brainstem and spinal motoneurons that are largely targeted by GABAergic interneurons, and we bring together data on the switch from excitatory to inhibitory effects of GABA, on the maturation of the GABAergic system and GABA(A)R subunits. We finally discuss the role of GABA and its GABA(A)R in immature hypoglossal motoneurons of the spastic (SPA) mouse, a model of human hyperekplexic syndrome.

Two opposite voltage-dependent currents control the unusual early development pattern of embryonic Renshaw cell electrical activity.

Renshaw cells (V1R) are excitable as soon as they reach their final location next to the spinal motoneurons and are functionally heterogeneous. Using multiple experimental approaches, in combination with biophysical modeling and dynamical systems theory, we analyzed, for the first time, the mechanisms underlying the electrophysiological properties of V1R during early embryonic development of the mouse spinal cord locomotor networks (E11.5-E16.5). We found that these interneurons are subdivided into several functional clusters from E11.5 and then display an unexpected transitory involution process during which they lose their ability to sustain tonic firing. We demonstrated that the essential factor controlling the diversity of the discharge pattern of embryonic V1R is the ratio of a persistent sodium conductance to a delayed rectifier potassium conductance. Taken together, our results reveal how a simple mechanism, based on the synergy of two voltage-dependent conductances that are ubiquitous in neurons, can produce functional diversity in embryonic V1R and control their early developmental trajectory.

[Acute and chronic pathologies of the thoracic aorta: From diagnosis to treatment]. / Pathologie aortique thoracique aiguë et chronique : du diagnostic au traitement.

Aortic pathologies benefit from imaging innovation and interventional radiology developments in order to improve patient management. At the early phase, vital risk should be considered. Whole body CT scan evaluate the complete aorta and its branches to assess the pathology and to choose the best approach between surgery or interventional radiology (fenestration, stentgraft, peripheral stenting). Algorithms, based on the understanding of the complications mechanisms and evolutive risk, modified the management specifically for aortic dissection. At chronic phase, GPs and angiologists should follow their patients in order to detect aortic complications and to treat cardiovascular risk factors. MRA is well indicated if possible.

Relaxation of synaptic inhibitory events as a compensatory mechanism in fetal SOD spinal motor networks.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting motor neurons (MNs) during late adulthood. Here, with the aim of identifying early changes underpinning ALS neurodegeneration, we analyzed the GABAergic/glycinergic inputs to E17.5 fetal MNs from SOD1G93A (SOD) mice in parallel with chloride homeostasis. Our results show that IPSCs are less frequent in SOD animals in accordance with a reduction of synaptic VIAAT-positive terminals. SOD MNs exhibited an EGABAAR10 mV more depolarized than in WT MNs associated with a KCC2 reduction. Interestingly, SOD GABAergic/glycinergic IPSCs and evoked GABAAR-currents exhibited a slower decay correlated to elevated [Cl-]i. Computer simulations revealed that a slower relaxation of synaptic inhibitory events acts as compensatory mechanism to strengthen GABA/glycine inhibition when EGABAAR is more depolarized. How such mechanisms evolve during pathophysiological processes remain to be determined, but our data indicate that at least SOD1 familial ALS may be considered as a neurodevelopmental disease.

NKCC1 cotransporter inactivation underlies embryonic development of chloride-mediated inhibition in mouse spinal motoneuron.

Early in development, GABA and glycine exert excitatory action that turns to inhibition due to modification of the chloride equilibrium potential (E(Cl)) controlled by the KCC2 and NKCC1 transporters. This switch is thought to be due to a late expression of KCC2 associated with a NKCC1 down-regulation. Here, we show in mouse embryonic spinal cord that both KCC2 and NKCC1 are expressed and functional early in development (E11.5-E13.5) when GABA(A) receptor activation induces strong excitatory action. After E15.5, a switch occurs rendering GABA unable to provide excitation. At these subsequent stages, NKCC1 becomes both inactive and less abundant in motoneurons while KCC2 remains functional and hyperpolarizes E(Cl). In conclusion, in contrast to other systems, the cotransporters are concomitantly expressed early in the development of the mouse spinal cord. Moreover, whereas NKCC1 follows a classical functional extinction, KCC2 is highly expressed throughout both early and late embryonic life.

Infrainguinal cutting balloon angioplasty in de novo arterial lesions.

BACKGROUND: This prospective, non-randomized study evaluated the short- and mid-term feasibility, safety, primary patency, and limb salvage of cutting balloon percutaneous transluminal angioplasty (CB-PTA) for the treatment of peripheral arterial occlusive disease (PAOD). METHODS AND RESULTS: All data were collected for 128 consecutive patients who underwent CB-PTA to improve infrainguinal arterial circulation between January 2003 and July 2007. One-hundred thirty-five limbs with PAOD (claudication, n = 19; critical limb ischemia [CLI], n = 116) were treated. Patency was evaluated by clinical examination and duplex ultrasonography. A total of 203 lesions (183 stenoses, 20 occlusions) were treated in 66 femoropopliteal and 69 infrapopliteal arterial segments. The TransAtlantic Inter-Societal Consensus (TASC) classification of the primary lesions was A in 41.5%, B in 45.2%, C in 8.2%, and D 5.1%. Mean follow-up was 16.1 +/- 9.7 months. The overall technical success rate was 96.3% and the complication rate was 8.9%. There were two (1.5%) perioperative deaths. The primary patency rate was 82.1% at 12- and 24-months in patients with claudication (femoropopliteal lesions). The 1- and 2-year results for femoropopliteal and infrapopliteal lesions in patients with CLI were: primary patency 64.4% and 51.9 %, respectively; limb salvage 84.2% and 76.9%; survival 92.6% and 88.5%. More distal lesions and TASC classification were significant independent risk factors for outcome (P < .05). Treatment of multiple segment lesions was an independent predictor of a favorable outcome (P = .04). CONCLUSION: CB-PTA is safe and feasible for the treatment of infrainguinal arterial occlusive disease, with relatively low mid-term restenosis rates compared to other endovascular treatments. However, these data cannot be extrapolated to potential outcomes for lesions >10 cm in length. Further follow-up will be necessary to evaluate the long-term results of CB-PTA.