Post-acute delivery of α5-GABAA antagonist, S 44819, improves functional recovery in juvenile rats following stroke

Lebrun, Florent; Violle, Nicolas; Letourneur, Annelise; Muller, Christophe; Fischer, Nicolas; Levilly, Anthony; Orset, Cyrille; Sors, Aurore; Vivien, Denis

doi:10.1016/j.expneurol.2021.113881

Cited by 1 publication

(1 citation statement)

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“…Immediately after stroke, during the hyperacute phase, hyperinhibition of the perilesional cortical areas prevents additional tissue damage due to ischemia-induced excitotoxicity (80)(81)(82). However, the persistence of hyperinhibition over time was correlated with worse motor outcomes (27,28), and pharmacological reduction in GABAergic inhibition led to better recovery in animal models (27,83,84). Further evidence has confirmed this last point by linking better motor recovery with a period of plasticity driven by molecular changes, such as cellular excitability (85), or by sustained disinhibition during the first weeks poststroke.…”

Section: Disinhibition Supports Motor Recoverymentioning

confidence: 99%

Brain oscillatory modes as a proxy of stroke recovery

harquel¹,

Hummel

2023

Preprint

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Stroke is the leading cause of long-term disability, making the search for successful rehabilitation treatment one of the most important public health issues. A better understanding of the neural mechanisms underlying impairment and recovery and the development of associated markers is critical for tailoring treatments to each individual patient with the ultimate goal of maximizing therapeutic outcomes. Here, we used a novel and powerful method consisting of combined transcranial magnetic stimulation (TMS) and multichannel electroencephalography (EEG) to analyze TMS-induced brain oscillations in a large cohort of 60 stroke patients from the acute to the early-chronic phase after a stroke. A data-driven parallel factor analysis (PARAFAC) approach to tensor decomposition allowed to detect brain oscillatory modes specifically centered on the θ, α and β frequency bands. In the acute stage, patients presented a general slowdown of these oscillatory modes, highlighting stroke-induced perturbations within thalamocortical processing. Furthermore, low-frequency modes evolved across stroke stages, according to the extent of motor recovery, associated with changes in GABAergic intracortical inhibition. Overall, these longitudinal changes provide novel insights into the ongoing functional reorganization of brain networks after a stroke and the underlying mechanisms. Notably, we propose that the observed α-mode decrease corresponds to a beneficial disinhibition phase between the subacute and early-chronic stages that fosters structural and functional plasticity and facilitates recovery. Monitoring this phenomenon at the individual patient level will provide critical information for phenotyping patients, developing electrophysiological biomarkers and refining therapies based on personalized excitatory/inhibitory neuromodulation using noninvasive or invasive brain stimulation techniques.

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