Biology subjects

Lacour, S.

Publications and source records attributed to Lacour, S..

5 recordsLinked to original sources

bioRxiv2024

THE NEURONAL ARCHITECTURE OF AUTONOMIC DYSREFLEXIA

Autonomic dysreflexia is a life-threatening medical condition characterized by episodes of uncontrolled hypertension that occur in response to sensory stimuli after spinal cord injury (SCI)1-7. The fragmented understanding of the mechanisms underlying autonomic dysreflexia hampers the development of therapeutic strategies to manage this condition, leaving people with SCI at daily risk of heart attack and stroke8-18. Here, we expose the complete de novo neuronal architecture that develops after SCI and causes autonomic dysreflexia. In parallel, we uncover a competing, yet overlapping neuronal architecture activated by epidural electrical stimulation of the spinal cord that safely regulates blood pressure after SCI. The discovery that these adversarial neuronal architectures converge onto a single neuronal subpopulation provided a blueprint for the design of a mechanism-based intervention that reversed autonomic dysreflexia in mice, rats, and humans with SCI. These results establish a path for the effective treatment of autonomic dysreflexia in people with SCI.

neuroscience↗

bioRxiv2023

Tick-borne flavivirus NS5 antagonizes interferon signaling by inhibiting the catalytic activity of TYK2

The mechanisms utilized by different flaviviruses to evade antiviral functions of interferons are varied and incompletely understood. Using virological approaches, biochemical assays and mass spectrometry analysis, we report here that the NS5 protein of tick-borne encephalitis virus (TBEV) and Louping Ill virus (LIV), two related tick-borne flaviviruses, antagonize JAK-STAT signaling through interactions with tyrosine kinase 2 (TYK2). Co-immunoprecipitation (co-IP) experiments, yeast gap-repair assays, computational protein-protein docking and functional studies identified a stretch of 10 residues of the RNA dependent RNA polymerase domain of tick-borne flavivirus NS5, but not mosquito-borne NS5, that is critical for interaction with the TYK2 kinase domain. Additional co-IP assays performed with several TYK2 orthologs revealed that the interaction was conserved across mammal species. In vitro kinase assays showed that TBEV and LIV NS5 reduced the catalytic activity of TYK2. Our results thus illustrate a novel mechanism by which viruses suppress the interferon response. TeaserInhibition of the catalytic activity of a key kinase of the JAK/STAT pathway by a viral protein

microbiology↗

bioRxiv2023

Neural stimulation hardware for the selective intrafascicular modulation of the vagus nerve

The neural stimulation of the vagus nerve is able to modulate various functions of the parasympathetic response in different organs. The stimulation of the vagus nerve is a promising approach to treating inflammatory diseases, obesity, diabetes, heart failure, and hypertension. The complexity of the vagus nerve requires highly selective stimulation, allowing the modulation of target-specific organs without side effects. Here, we address this issue by adapting a neural stimulator and developing an intraneural electrode for the particular modulation of the vagus nerve. The neurostimulator parameters such as amplitude, pulse width, and pulse shape were modulated. Single-, and multi-channel stimulation was performed at different amplitudes. For the first time, I polyimide thin-film neural electrode was designed for the specific stimulation of the vagus nerve. In vivo experiments were performed in the adult minipig to validate to elicit electrically evoked action potentials and to modulate physiological functions selectively, validating the selectivity of intraneural stimulation. Electrochemical tests of the electrode and the neurostimulator showed that the stimulation hardware was working correctly. Stimulating the porcine vagus nerve resulted in selective modulation of the vagus nerve. Alpha, beta, and theta waves could be distinguished during single- and multi-channel stimulation. We have shown that the here presented system is able to activate the vagus nerve selectively and can therefore modulate the heart rate, diastolic pressure, and systolic pressure. The here presented system may be used to restore the cardiac loop after denervation by implementing biomimetic stimulation patterns. Presented methods may be used to develop intraneural electrodes adapted for various applications.

bioengineering↗

bioRxiv2020

Electrical Stimulation Of The Cervical Dorsal Roots Enables Functional Arm And Hand Movements In Monkeys With Cervical Spinal Cord Injury

Recovering arm control is a top priority for people with paralysis. Unfortunately, the complexity of the neural mechanisms underlying arm control practically limited the effectiveness of neurotechnology approaches. Here, we exploited the neural function of surviving spinal circuits to restore voluntary arm and hand control in three monkeys with spinal cord injury using spinal cord stimulation. Our neural interface leverages the functional organization of the dorsal roots to convey artificial excitation via electrical stimulation to relevant spinal segments at appropriate movement phases. Stimulation bursts targeting specific spinal segments produced sustained arm movements enabling monkeys with arm paralysis to perform an unconstrained reach-and-grasp task. Stimulation specifically improved strength, task performances and movement quality. Electrophysiology suggested that residual descending inputs were necessary to produce coordinated movements. The efficacy and reliability of our approach hold realistic promises of clinical translation.

bioengineering↗

bioRxiv2020

RECRUITMENT OF UPPER-LIMB MOTONEURONS WITH EPIDURAL ELECTRICAL STIMULATION OF THE PRIMATE CERVICAL SPINAL CORD

Epidural electrical stimulation (EES) of lumbosacral sensorimotor circuits improves leg motor control in animals and humans with spinal cord injury (SCI). Upper-limb motor control involves similar circuits, located in the cervical spinal cord, suggesting that EES could also improve arm and hand movements after quadriplegia. However, the ability of cervical EES to selectively modulate specific upper-limb motor nuclei remains unclear. Here, we combined a realistic computational model of EES of the cervical spinal cord with experiments in macaque monkeys to explore the mechanisms of this modulation and characterize the recruitment selectivity of cervical stimulation interfaces. Our results indicate that interfaces with lateral electrodes can target individual posterior roots and achieve selective modulation of arm motoneurons via the direct recruitment of pre-synaptic pathways. Intraoperative recordings suggested similar properties in humans. These results provide a framework for the design of neuro-technologies to improve arm and hand control in humans with quadriplegia.

bioengineering↗