Toward an Adapted Neurofeedback for Post-stroke Motor Rehabilitation: State of the Art and Perspectives

International audienceStroke is a severe health issue, and motor recovery after stroke remains an important challenge in the rehabilitation field. Neurofeedback (NFB), as part of a brain–computer interface, is a technique for modulating brain activity using on-line feedback that has proved to be useful in motor rehabilitation for the chronic stroke population in addition to traditional therapies. Nevertheless, its use and applications in the field still leave unresolved questions. The brain pathophysiological mechanisms after stroke remain partly unknown, and the possibilities for intervention on these mechanisms to promote cerebral plasticity are limited in clinical practice. In NFB motor rehabilitation, the aim is to adapt the therapy to the patient’s clinical context using brain imaging, considering the time after stroke, the localization of brain lesions, and their clinical impact, while taking into account currently used biomarkers and technical limitations. These modern techniques also allow a better understanding of the physiopathology and neuroplasticity of the brain after stroke. We conducted a narrative literature review of studies using NFB for post-stroke motor rehabilitation. The main goal was to decompose all the elements that can be modified in NFB therapies, which can lead to their adaptation according to the patient’s context and according to the current technological limits. Adaptation and individualization of care could derive from this analysis to better meet the patients’ needs. We focused on and highlighted the various clinical and technological components considering the most recent experiments. The second goal was to propose general recommendations and enhance the limits and perspectives to improve our general knowledge in the field and allow clinical applications. We highlighted the multidisciplinary approach of this work by combining engineering abilities and medical experience. Engineering development is essential for the available technological tools and aims to increase neuroscience knowledge in the NFB topic. This technological development was born out of the real clinical need to provide complementary therapeutic solutions to a public health problem, considering the actual clinical context of the post-stroke patient and the practical limits resulting from it

Plocabulin, a novel tubulin-binding agent, inhibits angiogenesis by modulation of microtubule dynamics in endothelial cells

BACKGROUND: Vascular supply of tumors is one of the main targets for cancer therapy. Here, we investigated if plocabulin (PM060184), a novel marine-derived microtubule-binding agent, presents antiangiogenic and vascular-disrupting activities. METHODS: The effects of plocabulin on microtubule network and dynamics were studied on HUVEC endothelial cells. We have also studied its effects on capillary tube structures formation or destabilization in three-dimensional collagen matrices. In vivo experiments were performed on different tumor cell lines. RESULTS: In vitro studies show that, at picomolar concentrations, plocabulin inhibits microtubule dynamics in endothelial cells. This subsequently disturbs the microtubule network inducing changes in endothelial cell morphology and causing the collapse of angiogenic vessels, or the suppression of the angiogenic process by inhibiting the migration and invasion abilities of endothelial cells. This rapid collapse of the endothelial tubular network in vitro occurs in a concentration-dependent manner and is observed at concentrations lower than that affecting cell survival. The in vitro findings were confirmed in tumor xenografts where plocabulin treatment induced a large reduction in vascular volume and induction of extensive necrosis in tumors, consistent with antivascular effects. CONCLUSIONS: Altogether, these data suggest that an antivascular mechanism is contributing to the antitumor activities of plocabulin

Plocabulin, a novel tubulin-binding agent, inhibits angiogenesis by modulation of microtubule dynamics in endothelial cells

BACKGROUND: Vascular supply of tumors is one of the main targets for cancer therapy. Here, we investigated if plocabulin (PM060184), a novel marine-derived microtubule-binding agent, presents antiangiogenic and vascular-disrupting activities. METHODS: The effects of plocabulin on microtubule network and dynamics were studied on HUVEC endothelial cells. We have also studied its effects on capillary tube structures formation or destabilization in three-dimensional collagen matrices. In vivo experiments were performed on different tumor cell lines. RESULTS: In vitro studies show that, at picomolar concentrations, plocabulin inhibits microtubule dynamics in endothelial cells. This subsequently disturbs the microtubule network inducing changes in endothelial cell morphology and causing the collapse of angiogenic vessels, or the suppression of the angiogenic process by inhibiting the migration and invasion abilities of endothelial cells. This rapid collapse of the endothelial tubular network in vitro occurs in a concentration-dependent manner and is observed at concentrations lower than that affecting cell survival. The in vitro findings were confirmed in tumor xenografts where plocabulin treatment induced a large reduction in vascular volume and induction of extensive necrosis in tumors, consistent with antivascular effects. CONCLUSIONS: Altogether, these data suggest that an antivascular mechanism is contributing to the antitumor activities of plocabulin

Additional file 2: Table S1. of Plocabulin, a novel tubulin-binding agent, inhibits angiogenesis by modulation of microtubule dynamics in endothelial cells

Microtubule dynamics parameters for HUVEC cells treated with PM060184. EB3-GFP expressing HUVEC cells were exposed to 0.01, 0.03 or 0.1 nM plocabulin for one hour. Microtubule dynamics was then analyzed by confocal fluorescence microscopy. Kymographs of microtubule plus end dynamics were made and analyzed with the MTrackJ plugin running on the ImageJ software. Microtubule length changes ≥ 0.3 μm between two consecutive time points were considered as growth or shortening events, while changes < 0.3 μm were considered as pause events; only events starting and finishing within the recording were analyzed. Speed and distance were calculated for each growth event and were then averaged. Catastrophe frequency was calculated by dividing the number of catastrophes (transition from growth or pause to shortening) by the sum of growth and pause durations. For each condition, at least 10 microtubules per cell, in 10 cells in three independent experiments were analyzed. (DOCX 15 kb

Additional file 1: Figure S1. of Plocabulin, a novel tubulin-binding agent, inhibits angiogenesis by modulation of microtubule dynamics in endothelial cells

(A) Effects of plocabulin on HUVEC cell morphology and microtubule mass by fluorescence microscopy. Cells were cultured in the absence or presence of increasing concentrations of plocabulin at different time intervals. Cells were then stained for α-tubulin (red) and nuclei (blue). (B) Effects of plocabulin on HMEC-1 cell morphology and microtubule mass by fluorescence microscopy. Cells were cultured in the absence or presence of increasing concentrations of plocabulin at different time intervals. Cells were then stained for α-tubulin (red) and nuclei (blue). (PDF 340 kb

Impact of Number of Passes Before Rescue Therapy in Thrombectomy for Basilar Artery Strokes

Background When standard endovascular thrombectomy techniques fail to achieve a successful recanalization, it is often necessary to use rescue therapies (RTs). RTs are more commonly used in basilar artery occlusions and conventionally thought to represent “a last resort option.” We sought to study the outcomes of basilar artery occlusion patients who received RT, and further hypothesize that the number of instrumental passes before initiation of RT may be associated with increased risk for poor clinical outcomes. Methods We performed a retrospective analysis of the ETIS (“Endovascular Treatment in Ischemic Stroke”) registry. Our primary analysis included 277 patients who underwent thrombectomy for basilar artery occlusion, of whom 74 patients (26.7%) who received RT, defined as the use of intra‐arterial drugs, angioplasty, or stenting. Primary outcome measures included successful or complete reperfusion (final modified thrombolysis in cerebral infarction ≥2b or 3), functional independence (modified Rankin scale of 0–2), and mortality at 3 months. Results RT patients were more likely to have an atherosclerotic cause than non‐RT patients (46/74 [62.2%] versus 38/203 [18.7%]), were more likely to die (42/74 [56.8%] versus 73/203 [36.0%]), and were less likely to achieve functional independence (12/74 [16.2%] versus 84/203 [41.4%]). In the RT cohort, 17 of 74 patients (23.0%) had 1 pass before RT initiation, and 8 of 17 (47.1%) achieved a modified Rankin scale score of 0 to 2 at 3 months, with a mortality rate of 23.5% (4/17). The chance of achieving good clinical outcome decreased with each additional pass, whereas mortality increased. The odds of mortality at 3 months were highest in the >3 passes group, with an odds ratio of 10.29 (95% CI, 2.42–43.81) compared with 1 pass. None of the 25 patients with >3 passes before RT achieved 3‐month functional independence. Conclusions There is a significant correlation between the number of passes before initiation of RT and 3‐month clinical outcomes in basilar artery occlusion patients

Successful Thrombectomy Improves Functional Outcome in Tandem Occlusions with a Large Ischemic Core

International audienceBackground: Emergent stenting in tandem occlusions and mechanical thrombectomy (MT) of acute ischemic stroke related to large vessel occlusion (LVO-AIS) with a large core are tested independently. We aim to assess the impact of reperfusion with MT in patients with LVO-AIS with a large core and a tandem occlusion and to compare the safety of reperfusion between large core with tandem and nontandem occlusions in current practice. Methods: We analyzed data of all consecutive patients included in the prospective Endovascular Treatment in Ischemic Stroke Registry in France between January 2015 and March 2023 who presented with a pretreatment ASPECTS (Alberta Stroke Program Early CT Score) of 0–5 and angiographically proven tandem occlusion. The primary end point was a favorable outcome defined by a modified Rankin Scale (mRS) score of 0–3 at 90 days. Results: Among 262 included patients with a tandem occlusion and ASPECTS 0–5, 203 patients (77.5%) had a successful reperfusion (modified Thrombolysis in Cerebral Infarction grade 2b-3). Reperfused patients had a favorable shift in the overall mRS score distribution (adjusted odds ratio [aOR], 1.57 [1.22–2.03]; P < 0.001), higher rates of mRS score 0–3 (aOR, 7.03 [2.60–19.01]; P < 0.001) and mRS score 0–2 at 90 days (aOR, 3.85 [1.39–10.68]; P = 0.009) compared with nonreperfused. There was a trend between the occurrence of successful reperfusion and a decreased rate of symptomatic intracranial hemorrhage (aOR, 0.5 [0.22–1.13]; P = 0.096). Similar safety outcomes were observed after large core reperfusion in tandem and nontandem occlusions. Conclusions: Successful reperfusion was associated with a higher rate of favorable outcome in large core LVO-AIS with a tandem occlusion, with a safety profile similar to nontandem occlusion