Biology subjects

Navarro, X.

Publications and source records attributed to Navarro, X..

8 recordsLinked to original sources

bioRxiv2026

Advances in Thin-Film Graphene Neurotechnology for Chronic Nerve Stimulation and Recording

Neurotechnology is being explored for restoring sensorimotor functions after paralysis or amputation, which requires peripheral nerve interfaces that are selective, bidirectional, and chronically stable. Reduced graphene oxide (rGO)-based microelectrodes offer low impedance and a high charge-injection limit; however, long-term in vivo performance has been limited by the durability of encapsulation. Here, we introduce a 10 {micro}m-thick transverse intrafascicular multichannel electrode (TIME) with a hybrid polyimide-Al2O3 encapsulation engineered to improve fabrication yield, electrode-to-electrode uniformity, and device stability. In vitro, devices maintained near-ideal capacitive behaviour after accelerated ageing (3 months in PBS at 57 {degrees}C) and sustained 109 biphasic stimulation pulses without detectable electrochemical degradation. In vivo, the arrays recorded compound nerve action potentials after one month and enabled selective activation of distinct peripheral nerve fibres with comparatively low current thresholds during four months of follow-up, remaining below the device maximum injectable current. Together, these results demonstrate that combining graphene microelectrodes with a thin hybrid encapsulation improves chronic reliability of intraneural thin-film interfaces and helps to close the gap between laboratory prototypes and clinically relevant neuroprosthetic systems.

bioengineering↗

bioRxiv2024

Temporary cerebral ischaemia impairs thromboxane A2 constriction and induces hypertrophic remodelling in peripheral mesenteric arteries of hypertensive rats: limited reversal despite long-term suberoylanilide hydroxamic acid cerebroprotection

Stroke induces brain injury, especially severe in hypertensive patients, and elevates mortality rates through non-neurological complications. However, the potential effects of a transient ischaemic episode on the peripheral vasculature of hypertensive individuals remain unclear. Here, we investigated whether transient cerebral ischaemia (90 min)/reperfusion (1 or 8 days) induces alterations in mesenteric resistance artery (MRA) properties in adult male spontaneously hypertensive rats (SHR). In addition, we assessed whether the reported cerebroprotective effects of suberoylanilide hydroxamic acid (SAHA; 50 mg/kg; administered intraperitoneally at 1, 4, or 6 h after reperfusion onset) extend long-term and include beneficial effects on MRAs. Functional and structural properties of MRAs were examined at 1- and 8-days post-stroke. Nuclei distribution, collagen content, and oxidative stress were assessed. Ischaemic brain damage was evaluated longitudinally using magnetic resonance imaging. Following stroke, MRAs from SHR exhibited non-reversible impaired contractile responses to the thromboxane A2 receptor agonist U46619. Stroke increased the MRA cross-sectional area, wall thickness, and wall/lumen ratio due to augmented collagen deposition. These changes were partially sustained 8 days later. SAHA did not improve U46619-induced contractions but mitigated stroke-induced oxidative stress and collagen deposition, preventing MRA remodelling at 24 h of reperfusion. Furthermore, SAHA induced sustained cerebroprotective effects over 8 days, including reduced brain infarct and oedema, and improved neurological scores. However, SAHA had minimal impact on chronic MRA contractile impairments and remodelling. These findings suggest that stroke causes MRA changes in hypertensive subjects. While SAHA treatment offers long-term protection against brain damage, it cannot fully restore MRA alterations.

neuroscience↗

bioRxiv2024

Novel FKBP12 ligand promotes functional improvement in SOD1-G93A ALS mice

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with limited treatment options. ALS pathogenesis involves intricate processes within motor neurons (MNs), characterized by dysregulated Ca2+ influx and buffering in early ALS-affected MNs. This study proposes the modulation of ryanodine receptors (RyRs), key mediators of intracellular Ca2+, as a therapeutic target. A novel class of novel FKBP12 ligands that show activity as cytosolic calcium modulators through stabilizing RyR channel activity, were tested in the SOD1G93A mouse model of ALS. Different outcomes were used to assess treatment efficacy including electrophysiology, histopathology, neuromuscular function, and survival. Among the novel FKBP12 ligands, MP-010 was chosen for its central nervous system availability. Chronic administration of MP-010 to SOD1G93A mice produced a dose-dependent preservation of motor nerve conduction, with the 61 mg/kg dose significantly delaying the onset of motor impairment. This was accompanied by improved motor coordination, increased innervated endplates, and significant preservation of MNs in the spinal cord of treated mice. Notably, MP-010 treatment significantly extended lifespan by an average of 10 days compared to vehicle. In conclusion, FKBP12 ligands, particularly MP-010, exhibit promising neuroprotective effects in ALS, highlighting their potential as novel therapeutic agents. Further investigations into the molecular mechanisms and clinical translatability of these compounds are needed for their application in ALS treatment.

neuroscience↗

bioRxiv2023

Combining biophysical models and machine learning to optimize implant geometry and stimulation protocol for intraneural electrodes

ObjectivePeripheral nerve interfaces have the potential to restore sensory, motor, and visceral functions. In particular, intraneural interfaces allow targeting deep neural structures with high selectivity, even if their performance strongly depends upon the implantation procedure and the subjects anatomy. Currently, few alternatives exist for the determination of the target subject structural and functional anatomy, and statistical characterizations from cadaveric samples are limited because of their high cost. We propose an optimization workflow that can guide both the pre-surgical planning and the determination of maximally selective multisite stimulation protocols for implants consisting of several intraneural electrodes, and we characterize its performance in silico. We show that the availability of structural and functional information leads to very high performances and allows taking informed decisions on neuroprosthetic design. ApproachWe employ hybrid models (HMs) of neuromodulation in conjunction with a machine learning-based surrogate model to determine fiber activation under electrical stimulation, and two steps of optimization through particle swarm optimization (PSO) to optimize in silico implant geometry, implantation and stimulation protocols using morphological data from the human median nerve at a reduced computational cost. Main resultsOur method allows establishing the optimal geometry of multi-electrode transverse intra-fascicular multichannel electrode (TIME) implants, the optimal number of electrodes to implant, their optimal insertion, and a set of multipolar stimulation protocols that lead in silico to selective activation of all the muscles innervated by the human median nerve. SignificanceWe show how to use effectively HMs for optimizing personalized neuroprostheses for motor function restoration. We provide in-silico evidences about the potential of multipolar stimulation to increase greatly selectivity. We also show that the knowledge of structural and functional anatomies of the target subject leads to very high selectivity and motivate the development of methods for their in vivo characterization.

bioengineering↗

bioRxiv2022

Graphene-based thin film microelectrode technology for in vivo high resolution neural recording and stimulation

Neuroprosthetic technology aims to restore nervous system functionality in cases of severe damage or degeneration by recording and stimulating the electrical activity of the neural tissue. One of the key factors determining the quality of the neuroprostheses is the electrode material used to establish electrical communication with the neural tissue, which is subject to strict electrical, electrochemical, and mechanical specifications as well as biological and microfabrication compatibility requirements. This work presents a nanoporous graphene-based thin film technology and its engineering to form flexible neural implants. Bench measurements show that the developed microelectrodes offer low impedance and high charge injection capacity throughout millions of pulses. In vivo electrode performance was assessed in rodents both from brain surface and intracortically showing high-fidelity recording performance, while stimulation performance was assessed with an intrafascicular implant that demonstrated low current thresholds and high selectivity for activating subsets of axons within the sciatic nerve. Furthermore, the tissue biocompatibility of the devices was validated by chronic epicortical and intraneural implantation. Overall, this works describes a novel graphene-based thin film microelectrode technology and demonstrates its potential for high-precision neural interfacing in both recording and stimulation applications.

bioengineering↗

bioRxiv2021

A novel Alex3/Gαq protein complex regulating mitochondrial dynamics, dendritic complexity, and neuronal survival

In neurons, mitochondrial dynamics and trafficking are essential to provide the energy required for neurotransmission and neuronal activity. Recent studies point to GPCR and G proteins as important regulators of mitochondrial dynamics and energy metabolism. Here we show that activation of Gq negatively regulates mitochondrial dynamics and trafficking in neurons. Gq interacts with the mitochondrial trafficking protein Alex3. By generating a CNS-specific armcx3 knock-out mouse line, we demonstrate that Alex3 is required for Gq effects on mitochondrial dynamics and trafficking, and dendritic growth. Armcx3-deficient mice present decreased OXPHOS complex and ER stress response protein levels, which correlate with increased neuronal death, motor neuron and neuromuscular synaptic loss, and severe motor alterations. Finally, we show that Alex3 disassembles from the Miro1/Gq complex upon calcium rise. These data uncover a novel Alex3/Gq complex that regulates neuronal mitochondrial dynamics and neuronal death and allows the control of mitochondrial functions by GPCRs.

cell biology↗

bioRxiv2020

Selective neuromodulation induced by alpha-based neurofeedback learning: A double-blind randomized study

The neuromodulation induced by neurofeedback training (NFT) remains a matter of debate. Investigating the modulation of brain activity specifically associated with NF requires controlling for multiple factors, such as reward, performance, congruency between task and targeted brain activity. This can be achieved using sham feedback (FB) control condition, equating all aspects of the experiment but the link between brain activity and FB. We aimed at investigating the modulation of individual alpha EEG activity induced by NFT in a double-blind, randomized, sham-controlled study. Forty-eight healthy participants were assigned to either NF (n=25) or control (n=23) group and performed alpha upregulation training (over 12 weeks) with a wearable EEG device. Participants of the NF group received FB based on their individual alpha activity. The control group received the auditory FB of participants of the NF group. An increase of alpha activity across training sessions was observed in the NF group only (p<0.001). This neuromodulation was selective in that it was not observed for theta (4-8Hz) and low beta (13-18Hz) activities. While alpha upregulation was found in the NF group only, psychological outcome variables showed increased feeling of control, decreased anxiety level and increased relaxation feeling in both the NF and control groups, without any significant difference between groups. This is interpreted in terms of learning context and placebo effects. Our results pave the way to self-learnt, NF-based neuromodulation with light-weighted, wearable EEG systems.

neuroscience↗

bioRxiv2019

Stability of Thin-Film Metallization in Flexible Stimulation Electrodes: Analysis and Improvement of in vivo Performance

Micro-fabricated neural interfaces based on polyimide (PI) are achieving increasing importance in translational research. The ability to produce well-defined micro-structures with properties that include chemical inertness, mechanical flexibility and low water uptake are key advantages for these devices. This paper reports the development of the transverse intrafascicular multichannel electrode (TIME) used to deliver intraneural sensory feedback to an upper-limb amputee in combination with a sensorized hand prosthesis. A first-in-human study limited to 30 days was performed. About 90 % of the stimulation contact sites of the TIMEs maintained electrical functionality and stability during the full implant period. However, optical analysis post-explantation revealed that 62.5 % of the stimulation contacts showed signs of mechanical damage at the metallization-PI interface. Such damage likely occurred due to handling during explantation and subsequent analysis, since a significant change in impedance was not observed in vivo. Nevertheless, whereas device integrity is mandatory for long-term functionality in chronic implantation, measures to increase the bonding strength of the metallization-PI interface deserve further investigation. We report here that silicon carbide (SiC) is an effective adhesion-promoting layer resisting heavy electrical stimulation conditions in vivo. Optical analysis of the new electrodes revealed that the metallization remained unaltered after delivering over 14 million pulses in vivo without signs of delamination at the metallization-PI interface. Reliable adhesion of thin-film metallization to substrate has been proven using SiC, improving the potential transfer of micro-fabricated neural electrodes for chronic clinical applications.

bioengineering↗