- MeSH
- Nerve Degeneration MeSH
- Cats MeSH
- Sciatic Nerve physiology MeSH
- Neuronal Plasticity MeSH
- Nerve Regeneration MeSH
- Synapses physiology MeSH
- Animals MeSH
- Check Tag
- Cats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Donor nerve selection is a crucial factor in determining clinical outcomes of facial reanimation. Although dual innervation approaches using two neurotizers have shown promise, there is a lack of evidence-based comparison in the literature. Furthermore, no animal model of dual reinnervation has yet been published. This study aimed to establish such a model and verify its technical and anatomical feasibility by performing dual-innervated reanimation approaches in Wistar rats. METHODS: Fifteen Wistar rats were divided into four experimental groups and one control group. The sural nerve was exposed and used as a cross-face nerve graft (CFNG), which was then anastomosed to the contralateral buccal branch of the facial nerve through a subcutaneous tunnel on the forehead. The CFNG, the masseteric nerve (MN), and the recipient nerve were coapted in one or two stages. The length and width of the utilized structures were measured under an operating microscope. Return of whisker motion was visually confirmed. RESULTS: Nine out of the eleven rats that underwent surgery survived the procedure. Whisker motion was observed in all experimental animals, indicating successful reinnervation. The mean duration of the surgical procedures did not differ significantly between the experimental groups, ensuring similar conditions for all groups. CONCLUSIONS: Our experimental study confirmed that the proposed reanimation model in Wistar rats is anatomically and technically feasible, with a high success rate, and shows good prospects for future experiments.
- Keywords
- axonal regeneration, cross facial nerve graft, dual innervation, facial palsy, facial reanimation, neurotization,
- MeSH
- Facial Paralysis * surgery MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Facial Nerve * surgery physiology MeSH
- Sural Nerve surgery MeSH
- Rats, Wistar MeSH
- Nerve Regeneration * physiology MeSH
- Vibrissae physiology innervation MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Experimental and theoretical studies have shown that ephaptic coupling leads to the synchronisation and slowing down of spikes propagating along the axons within peripheral nerve bundles. However, the main focus thus far has been on a small number of identical axons, whereas realistic peripheral nerve bundles contain numerous axons with different diameters. Here, we present a computationally efficient spike propagation model, which captures the essential features of propagating spikes and their ephaptic interaction, and facilitates the theoretical investigation of spike volleys in large, heterogeneous fibre bundles. We first lay out the theoretical basis to describe how the spike in an active axon changes the membrane potential of a passive axon. These insights are then incorporated into the spike propagation model, which is calibrated with a biophysically realistic model based on Hodgkin-Huxley dynamics. The fully calibrated model is then applied to fibre bundles with a large number of axons and different types of axon diameter distributions. One key insight of this study is that the heterogeneity of the axonal diameters has a dispersive effect, and that a higher level of heterogeneity requires stronger ephaptic coupling to achieve full synchronisation between spikes.
BACKGROUND: It is difficult to repair nerve if proximal stump is unavailable or autogenous nerve grafts are insufficient for reconstructing extensive nerve damage. Therefore, alternative methods have been developed, including lateral anastomosis based on axons' ability to send out collateral sprouts into denervated nerve. The different capacity of a sensory or motor axon to send a sprout is controversial and may be controlled by cytokines and/or neurotrophic factors like ciliary neurotrophic factor (CNTF). The aim of the present study was to quantitatively assess collateral sprouts sent out by intact motor and sensory axons in the end-to-side neurorrhaphy model following intrathecal administration of CNTF in comparison with phosphate buffered saline (vehiculum) and Cerebrolysin. The distal stump of rat transected musculocutaneous nerve (MCN) was attached in an end-to-side fashion with ulnar nerve. CNTF, Cerebrolysin and vehiculum were administered intrathecally for 2 weeks, and all animals were allowed to survive for 2 months from operation. Numbers of spinal motor and dorsal root ganglia neurons were estimated following their retrograde labeling by Fluoro-Ruby and Fluoro-Emerald applied to ulnar and musculocutaneous nerve, respectively. Reinnervation of biceps brachii muscles was assessed by electromyography, behavioral test, and diameter and myelin sheath thickness of regenerated axons. RESULTS: Vehiculum or Cerebrolysin administration resulted in significantly higher numbers of myelinated axons regenerated into the MCN stumps compared with CNTF treatment. By contrast, the mean diameter of the myelinated axons and their myelin sheath thickness in the cases of Cerebrolysin- or CNTF-treated animals were larger than were those for rats treated with vehiculum. CNTF treatment significantly increased the percentage of motoneurons contributing to reinnervation of the MCN stumps (to 17.1%) when compared with vehiculum or Cerebrolysin treatments (at 9.9 or 9.6%, respectively). Reduced numbers of myelinated axons and simultaneously increased numbers of motoneurons contributing to reinnervation of the MCN improved functional reinnervation of the biceps brachii muscle after CNTF treatment. CONCLUSION: The present experimental study confirms end-to-side neurorrhaphy as an alternative method for reconstructing severed peripheral nerves. CNTF promotes motor reinnervation of the MCN stump after its end-to-side neurorrhaphy with ulnar nerve and improves functional recovery of the biceps brachii muscle.
- MeSH
- Axons drug effects MeSH
- Ciliary Neurotrophic Factor administration & dosage MeSH
- Rats MeSH
- Motor Neurons drug effects MeSH
- Nerve Transfer methods MeSH
- Musculocutaneous Nerve drug effects injuries physiopathology MeSH
- Peripheral Nerve Injuries physiopathology therapy MeSH
- Rats, Wistar MeSH
- Nerve Regeneration drug effects physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Ciliary Neurotrophic Factor MeSH
OBJECTIVE: The aim of the study was to find how a simultaneous impairment of the CNS (cellular brain edema induced by water intoxication) and PNS (blockade of the right forelimb brachial plexus by local anesthewtic - Marcaine) affects spontaneous locomotor activity of adult rats. METHODS: Rats were divided into groups of animals without water intoxication (without WI) - A,B,C, and those that were water intoxicated (induction of brain edema - after WI) - D,E,F. Both groups were further divided into intact ones (A,D), animals with PNS lesion (Marcaine) (B,E) and sham-operated animals (C,F). Locomotor activity (LA) of the rats was tested by the open field test. RESULTS: LA of rats with both CNS and PNS impairment (WI + Marcaine) was significantly suppressed compared to the activity of control rats. Comparison of LA of rats with a single lesion - PNS impairment only (Marcaine only), CNS lesion only (WI) to those animals with both lesions (WI + Marcaine) revealed even larger decrease of LA of rats with combined lesions, which represents a model of the dual diagnosis. Also the pattern of behaviour of rats in both sham operated groups was different, which apparently depended on water intoxication. CONCLUSION: The presented results show that the LA of rats with combined lesions is significantly lower compared to the activity of rats with a single lesion in the CNS or PNS. Results also indicate that the already induced endoneurial edema prevents subsequent accumulation of water applied to the intimate vicinity of the peripheral nervous structures.
- MeSH
- Brain Edema complications physiopathology MeSH
- Water Intoxication complications physiopathology MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Peripheral Nervous System Diseases complications physiopathology MeSH
- Motor Activity physiology MeSH
- Rats, Wistar MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Objective.Vagus nerve stimulation (VNS) is a promising approach for the treatment of a wide variety of debilitating conditions, including autoimmune diseases and intractable epilepsy. Much remains to be learned about the molecular mechanisms involved in vagus nerve regulation of organ function. Despite an abundance of well-characterized rodent models of common chronic diseases, currently available technologies are rarely suitable for the required long-term experiments in freely moving animals, particularly experimental mice. Due to challenging anatomical limitations, many relevant experiments require miniaturized, less invasive, and wireless devices for precise stimulation of the vagus nerve and other peripheral nerves of interest. Our objective is to outline possible solutions to this problem by using nongenetic light-based stimulation.Approach.We describe how to design and benchmark new microstimulation devices that are based on transcutaneous photovoltaic stimulation. The approach is to use wired multielectrode cuffs to test different stimulation patterns, and then build photovoltaic stimulators to generate the most optimal patterns. We validate stimulation through heart rate analysis.Main results.A range of different stimulation geometries are explored with large differences in performance. Two types of photovoltaic devices are fabricated to deliver stimulation: photocapacitors and photovoltaic flags. The former is simple and more compact, but has limited efficiency. The photovoltaic flag approach is more elaborate, but highly efficient. Both can be used for wireless actuation of the vagus nerve using light impulses.Significance.These approaches can enable studies in small animals that were previously challenging, such as long-termin vivostudies for mapping functional vagus nerve innervation. This new knowledge may have potential to support clinical translation of VNS for treatment of select inflammatory and neurologic diseases.
- Keywords
- flexible electronics, neuromodulation, optoelectronics, peripheral nerve stimulation, vagus nerve stimulation, wireless stimulator,
- MeSH
- Wireless Technology * MeSH
- Mice MeSH
- Vagus Nerve Stimulation * instrumentation MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The first step to make the theory of stochastic diffusion processes that arise in connection with single neuron description more understandable is reviewing the deterministic leaky-integrator model. After this step the general principles of simple stochastic models are summarized which clearly reveal that two different sources of noise, intrinsic and external, can be identified. Many possible strategies of neuronal coding exist and one of these, the rate coding, for which the stochastic modeling is relevant, is pursued further. The rate coding is reflected, in experimental as well as theoretical studies, by an input-output curve and its properties are reviewed for the most common stochastic diffusion models. The results for the simplest stochastic diffusion model, the Wiener process, are presented and from them strong limitations of this model can be understood. The most common diffusion model is the Ornstein-Uhlenbeck process, which is one substantial step closer to reality since the spontaneous changes of the membrane potential are included in the model. Both these models are characterized by an additive noise. Taking into account the state dependency of the changes caused by neuronal inputs, we derive models where the noise has a multiplicative effect on the membrane depolarization. Two of these models are compared with the Wiener and Ornstein-Uhlenbeck models. How to identify the parameters of the models, which is an unavoidable task for the models verification, is investigated. The time-variable input is taken into account in the last part of the paper. An intuitive approach is stressed throughout the review.
OBJECTIVE: Locomotion, rearing and grooming represent different forms of behaviour and motor activity in rats. In this study, changes in these activities were analysed in relation to impaired function of the nervous system by single and/or concomitant lesions representing an experimental model of the dual diagnosis. METHODS: 32 rats were divided into 4 groups of 8 rats: intact rats, rats with single lesion of peripheral nervous system (PNS) - Marcaine neuropathy, rats with single CNS lesion - cellular brain edema induced by water intoxication, and the concomitant lesions (combination of CNS and PNS lesion in one rat). Water intoxication was performed in a standard way by fractionated hyperhydration. The average time spent by locomotion, rearing and grooming was registered and analyzed using an open field test. RESULTS: All activities of the rats after water intoxication became inhibited due to the generally suppressive effect of brain edema. Lesion of PNS reduced activity in locomotion only, because for rearing and grooming activities, the function of the forelimb is not dominant. Combination of lesions (dual diagnosis) reduced locomotion and rearing activity more than single lesions, and enhances the stressogenic effect, which was manifested by a long periods of grooming. CONCLUSION: Results of our study confirmed the physiological and pathophysiological differences in the movement stereotype between locomotion, rearing and grooming caused by the characteristics and algorithms of the movements, which are inborn to rats - the dominant role of the forelimbs in locomotion, the dominant exploratory activity in rearing, and the precise syntactic movement pattern in grooming.
- MeSH
- Bupivacaine MeSH
- Behavior, Animal physiology MeSH
- Brain Edema physiopathology MeSH
- Water Intoxication physiopathology MeSH
- Rats MeSH
- Locomotion physiology MeSH
- Peripheral Nervous System Diseases chemically induced physiopathology MeSH
- Grooming physiology MeSH
- Motor Activity physiology MeSH
- Rats, Wistar MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Bupivacaine MeSH
INTRODUCTION: Peripheral nerve injury is a frequently encountered clinical problem that leads to functional losses at the long-term. Although microsurgical repair has been introduced to clinical practice in peripheral nerve injuries, unsatisfactory outcomes regarding functional recovery in target organ cause an increasing interest on studies about nerve injury and biology of the recovery in nerve injuries1. MATERIAL AND METHODS: Sciatic nerves of seventy adult Sprague Dewly rats were transected and primary anastomosis was performed. Rats were then divided into three groups: Control group, while 30 rats were repaired with sutures, and the remaining 30 were repaired with fibrin glue. After 30 days the rats were sacrified and the sciatic nerves were investigated histologically with morphometrical and statistical analyses. RESULTS: In microsurgical nerve repair, suture placement has been thought to cause hindrance to the sprouting axons and compress the blood supply to the fascicles, thereby impairing the regeneration of the transected nerve ends after repair, with possible neuroma formation. On the other hand, fibrin glue is a simple, effective technique, less time consuming than suturing. Another advantage of this suture-free technique is that it avoids injuring the axon with needles, and the lack of foreign bodies minimizes the inflammatory reaction. CONCLUSION: We recommend using fibrin glue as it demonstrates less inflammatory reaction, less scar tissue formation, it is less time consuming and provides better outcomes.
- Keywords
- Fibrin glue, sutures periph.,
- MeSH
- Anastomosis, Surgical MeSH
- Fibrin Tissue Adhesive * MeSH
- Rats MeSH
- Femoral Nerve * MeSH
- Sciatic Nerve * surgery MeSH
- Rats, Sprague-Dawley MeSH
- Sutures MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Fibrin Tissue Adhesive * MeSH
Homocysteinemia is a metabolic condition characterized by abnormally high level of homocysteine in the blood and is considered to be a risk factor for peripheral neuropathy. However, the cellular mechanisms underlying toxic effects of homocysteine on the processing of peripheral nociception have not yet been investigated comprehensively. Here, using a rodent model of experimental homocysteinemia, we report the causal association between homocysteine and the development of mechanical allodynia. Homocysteinemia-induced mechanical allodynia was reversed on pharmacological inhibition of T-type calcium channels. In addition, our in vitro studies indicate that homocysteine enhances recombinant T-type calcium currents by promoting the recycling of Cav3.2 channels back to the plasma membrane through a protein kinase C-dependent signaling pathway that requires the direct phosphorylation of Cav3.2 at specific loci. Altogether, these results reveal an unrecognized signaling pathway that modulates the expression of T-type calcium channels, and may potentially contribute to the development of peripheral neuropathy associated with homocysteinemia.
- MeSH
- Cell Membrane metabolism MeSH
- Homocysteine blood MeSH
- Hyperalgesia etiology metabolism MeSH
- Hyperhomocysteinemia complications MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Peripheral Nervous System Diseases etiology metabolism MeSH
- Nociception physiology MeSH
- Rats, Wistar MeSH
- Ganglia, Spinal metabolism MeSH
- Calcium metabolism MeSH
- Calcium Channels, T-Type metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Homocysteine MeSH
- Calcium MeSH
- Calcium Channels, T-Type MeSH