Biology subjects

Mughrabi, I.

Publications and source records attributed to Mughrabi, I..

3 recordsLinked to original sources

bioRxiv2022

Organ- and function-specific organization and bioelectronic modulation of vagus fascicles and fibers

Vagal fibers travel inside fascicles and form branches to innervate organs and regulate organ functions. Vagus nerve stimulation (VNS) therapies activate fibers non-selectively, often resulting in reduced efficacy and side effects from non-targeted organs. Transverse and longitudinal arrangement of fibers according to functions they mediate and organs they innervate is unknown, however it is crucial for selective VNS. Using microcomputed tomography, we found that, in swine, fascicles are arranged in 2 overlapping axes, with sensory and motor fascicles separated cephalad and merging caudad, and larynx-, heart- and lung-specific fascicles separated caudad and progressively merging cephalad. Using immunohistochemistry, we found that the distribution of single fibers is highly nonuniform: myelinated afferents and efferents occupy separate fascicles, unmyelinated efferents co-localize with myelinated afferents, and small unmyelinated afferents are widely distributed. Using a multi-contact cuff electrode, we delivered fascicular cervical VNS in anesthetized and awake swine. Compound action potentials, from distinct fiber types, and organ responses, including laryngeal muscle, cough, breathing, heart rate and blood pressure responses are elicited in a radially asymmetric manner, with consistent angular separations. These results indicate that vagal fibers are anatomically organized according to functions they mediate and organs they innervate and can be asymmetrically activated by fascicular cervical VNS.

neuroscience↗

bioRxiv2021

A Fully Implantable Wireless Bidirectional Neuromodulation System for Mice

Novel research in the field of bioelectronic medicine requires systems that pair high-performance neurostimulation and bio-signal acquisition hardware with advanced software signal processing and control algorithms. Although mice are the most commonly used animal in medical research, the size, weight, and power requirements of such systems either preclude their use or impose significant constraints on experimental design. Here, we describe a fully-implantable neuromodulation system suitable for use in mice, measuring 2.2 cm3 and weighing 2.8 g. A bidirectional wireless interface allows simultaneous readout of multiple physiological signals and complete control over stimulation parameters, and a wirelessly rechargeable battery provides a lifetime of up to 5 days on a single charge. The device was successfully implanted (N=12) and a functional neural interface (capable of inducing acute bradycardia) is demonstrated with functional lifetimes exceeding to three weeks. The design utilizes only commercially-available components and 3D-printed packaging, with the goal of accelerating discovery and translation of future bioelectronic therapeutics.

bioengineering↗

bioRxiv2021

Manipulation of stimulus waveform and frequency permits targeted fiber activation during vagus nerve stimulation in 2 rodent species

Afferent and efferent vagal fibers mediate bidirectional communication between the brain and visceral organs. Small, unmyelinated C-afferents constitute the majority of vagal fibers, play critical roles in numerous interoceptive circuits and autonomic reflexes in health and disease and may contribute to the efficacy and safety of vagus nerve stimulation (VNS). Selective engagement of C-afferents with electrical stimuli has not been feasible, due to the default fiber recruitment order: larger fibers first, smaller fibers last. Here, we determine and optimize an electrical stimulus that selectively engages vagal C-afferents. Intermittent KHz-frequency electrical stimulation (KES) activates motor and, preferentially, sensory vagal neurons in the brainstem. During KES, asynchronous activity of C-afferents increases, while that of larger fibers remains largely unchanged. In parallel, KES effectively blocks excitability of larger fibers while moderately suppressing excitability of C-afferents. By compiling selectivity indices in individual animals, we find that optimal KES parameters for C-afferents are >5KHz frequency and 7-10 times engagement threshold (xT) intensity in rats, 15-25xT in mice. These effects can be explained in computational models by how sodium channel responses to KES are shaped by axonal size and myelin. Our results indicate that selective engagement of vagal C-afferents is attainable by intermittent KES.

bioengineering↗