Assessment of the Effect of Autograft Orientation on Peripheral Nerve Regeneration Using Diffusion Tensor Imaging.

Purpose: Given no definite consensus on the accepted autograft orientation during peripheral nerve injury repair, we compare outcomes between reverse and normally oriented autografts using an advanced magnetic resonance imaging technique, diffusion tensor imaging.

Methods: Thirty-six female Sprague-Dawley rats were divided into 3 groups: sham-left sciatic nerve isolation without injury, reverse autograft-10-mm cut left sciatic nerve segment reoriented 180° and used to coapt the proximal and distal stumps, or normally oriented autograft-10-mm cut nerve segment kept in its normal orientation for coaptation. Animals underwent sciatic functional index and foot fault behavior studies at 72 hours, and then weekly.

Experimental studies of g-ratio MRI in ex vivo mouse brain.

This study aimed to experimentally evaluate a previously proposed MRI method for mapping axonal g-ratio (ratio of axon diameters, measured to the inner and outer boundary of myelin). MRI and electron microscopy were used to study excised and fixed brains of control mice and three mouse models of abnormal white matter. The results showed that g-ratio measured with MRI correlated with histological measures of myelinated axon g-ratio, but with a bias that is likely due to the presence of non-myelinated axons.

Loss of mTORC2 signaling in oligodendrocyte precursor cells delays myelination.

Myelin abnormalities are increasingly being recognized as an important component of a number of neurologic developmental disorders. The integration of many signaling pathways and cell types are critical for correct myelinogenesis. The PI3-K and mechanistic target of rapamycin (mTOR) pathways have been found to play key roles.

A novel conduit-based coaptation device for primary nerve repair.

Background: Conduit-based nerve repairs are commonly used for small nerve gaps, whereas primary repair may be performed if there is no tension on nerve endings. We hypothesize that a conduit-based nerve coaptation device will improve nerve repair outcomes by avoiding sutures at the nerve repair site and utilizing the advantages of a conduit-based repair.

Methods: The left sciatic nerves of female Sprague-Dawley rats were transected and repaired using a novel conduit-based device.

Immediate Enhancement of Nerve Function Using a Novel Axonal Fusion Device After Neurotmesis.

Background: The management of peripheral nerve injuries remains a large challenge for plastic surgeons. With the inability to fuse axonal endings, results after microsurgical nerve repair have been inconsistent. Our current nerve repair strategies rely upon the slow and lengthy process of axonal regeneration (~1 mm/d).

Bridging the Gap: Engineered Porcine-derived Urinary Bladder Matrix Conduits as a Novel Scaffold for Peripheral Nerve Regeneration.

Purpose: This study aims to compare engineered nerve conduits constructed from porcine-derived urinary bladder matrix (UBM) with the criterion-standard nerve autografts, for segmental loss peripheral nerve repairs.

Methods: Forty-eight Sprague-Dawley rats were divided into 2 groups. All underwent a 10-mm sciatic nerve gap injury.

Myelin volume fraction imaging with MRI.

MRI is a valuable tool to assess myelin during development and demyelinating disease processes. While multiexponential T and quantitative magnetization transfer measures correlate with myelin content, neither provides the total myelin volume fraction. In many cases correlative measures are adequate; but to assess microstructure of myelin, (e.

A novel therapy to promote axonal fusion in human digital nerves.

Background: Peripheral nerve injury can have a devastating impact on our military and veteran population. Current strategies for peripheral nerve repair include techniques such as nerve tubes, nerve grafts, tissue matrices, and nerve growth guides to enhance the number of regenerating axons. Even with such advanced techniques, it takes months to regain function.

Multi-compartment microscopic diffusion imaging.

This paper introduces a multi-compartment model for microscopic diffusion anisotropy imaging. The aim is to estimate microscopic features specific to the intra- and extra-neurite compartments in nervous tissue unconfounded by the effects of fibre crossings and orientation dispersion, which are ubiquitous in the brain. The proposed MRI method is based on the Spherical Mean Technique (SMT), which factors out the neurite orientation distribution and thus provides direct estimates of the microscopic tissue structure.

A novel technique using hydrophilic polymers to promote axonal fusion.

The management of traumatic peripheral nerve injury remains a considerable concern for clinicians. With minimal innovations in surgical technique and a limited number of specialists trained to treat peripheral nerve injury, outcomes of surgical intervention have been unpredictable. The inability to manipulate the pathophysiology of nerve injury (i.

Hypomyelination following deletion of Tsc2 in oligodendrocyte precursors.

Objective: While abnormalities in myelin in tuberous sclerosis complex (TSC) have been known for some time, recent imaging-based data suggest myelin abnormalities may be independent of the pathognomonic cortical lesions ("tubers"). Multiple mouse models of TSC exhibit myelination deficits, though the cell types responsible and the mechanisms underlying the myelin abnormalities remain unclear.

Methods: To determine the role of alterations in mTOR signaling in myelination, we generated a conditional knockout (CKO) mouse model using Cre-recombinase and the Olig2 promoter to inactivate the Tsc2 gene in oligodendrocyte precursor cells.

Quantitative analysis of mouse corpus callosum from electron microscopy images.

This article provides morphometric analysis of 72 electron microscopy images from control (n=4) and hypomyelinated (n=2) mouse corpus callosum. Measures of axon diameter and g-ratio were tabulated across all brains from two regions of the corpus callosum and a non-linear relationship between axon diameter and g-ratio was observed. These data are related to the accompanying research article comparing multiple methods of measuring g-ratio entitled 'A revised model for estimating g-ratio from MRI' (West et al.

Evaluation of diffusion kurtosis imaging in ex vivo hypomyelinated mouse brains.

Diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and DKI-derived white matter tract integrity metrics (WMTI) were experimentally evaluated ex vivo through comparisons to histological measurements and established magnetic resonance imaging (MRI) measures of myelin in two knockout mouse models with varying degrees of hypomyelination. DKI metrics of mean and radial kurtosis were found to be better indicators of myelin content than conventional DTI metrics. The biophysical WMTI model based on the DKI framework reported on axon water fraction with good accuracy in cases with near normal axon density, but did not provide additional specificity to myelination.

4.7-T diffusion tensor imaging of acute traumatic peripheral nerve injury.

Diagnosis and management of peripheral nerve injury is complicated by the inability to assess microstructural features of injured nerve fibers via clinical examination and electrophysiology. Diffusion tensor imaging (DTI) has been shown to accurately detect nerve injury and regeneration in crush models of peripheral nerve injury, but no prior studies have been conducted on nerve transection, a surgical emergency that can lead to permanent weakness or paralysis. Acute sciatic nerve injuries were performed microsurgically to produce multiple grades of nerve transection in rats that were harvested 1 hour after surgery.

A revised model for estimating g-ratio from MRI.

A key measure of white matter health is the g-ratio, which is defined as the ratio between the inner axon radius and the outer, myelinated, axon radius. Recent methods have been proposed to measure the g-ratio non-invasively using the relationship between two magnetic resonance imaging (MRI) measures. While this relationship is intuitive, it predicates on the simplifying assumption that g-ratio is constant across axons.

Antipsychotic drug-like effects of the selective M4 muscarinic acetylcholine receptor positive allosteric modulator VU0152100.

Accumulating evidence suggests that selective M4 muscarinic acetylcholine receptor (mAChR) activators may offer a novel strategy for the treatment of psychosis. However, previous efforts to develop selective M4 activators were unsuccessful because of the lack of M4 mAChR subtype specificity and off-target muscarinic adverse effects. We recently developed VU0152100, a highly selective M4 positive allosteric modulator (PAM) that exerts central effects after systemic administration.