Axon injury in the peripheral nervous system (PNS) induces a regeneration-associated gene (RAG) response. Atf3 (activating transcription factor 3) is such a RAG and ATF3's transcriptional activity might induce ‘effector’ RAGs (e.g. small proline rich protein 1a (Sprr1a), Galanin (Gal), growth-associated protein 43 (Gap43)) facilitating peripheral axon regeneration. We provide a first analysis of Atf3 mouse mutants in peripheral nerve regeneration. In Atf3 mutant mice, facial nerve regeneration and neurite outgrowth of adult ATF3-deficient primary dorsal root ganglia neurons was decreased. Using genome-wide transcriptomics, we identified a neuropeptide-encoding RAG cluster (vasoactive intestinal peptide (Vip), Ngf, Grp, Gal, Pacap) regulated by ATF3. Exogenous administration of neuropeptides enhanced neurite growth of Atf3 mutant mice suggesting that these molecules might be effector RAGs of ATF3's pro-regenerative function. In addition to the induction of growth-promoting molecules, we present data that ATF3 suppresses growth-inhibiting molecules such as chemokine (C-C motif) ligand 2. In summary, we show a pro-regenerative ATF3 function during PNS nerve regeneration involving transcriptional activation of a neuropeptide-encoding RAG cluster. ATF3 is a general injury-inducible factor, therefore ATF3-mediated mechanisms identified herein might apply to other cell and injury types.

A thorough knowledge of the anatomy of the vulnerable nerves and of variants in their course can lessen the risk of iatrogenic nerve injury. When such injuries arise, early diagnosis and planning of further management are the main determinants of outcome. If adequate nerve regeneration does not occur, surgical revision should optimally be performed 3 to 4 months after the injury, and 6 months afterward at the latest. On the other hand, if postoperative high resolution ultrasound reveals either complete transection of the nerve or a neuroma in continuity, surgery should be performed without any further delay. If the surgeon becomes aware of a nerve transection during the initial procedure, then either immediate end-to-end suturing or early secondary management after three weeks is indicated.

High-resolution ultrasonography is a noninvasive, readily applicable imaging modality, capable of depicting real-time static and dynamic morphological information concerning the peripheral nerves and their surrounding tissues. Continuous progress in ultrasonographic technology results in highly improved spatial and contrast resolution. Therefore, nerve imaging is possible to a fascicular level, and most peripheral nerves can now be depicted along their entire anatomical course. An increasing number of publications have evaluated the role of high-resolution ultrasonography in peripheral nerve diseases, especially in peripheral nerve entrapment. Ultrasonography has been shown to be a precious complementary tool for assessing peripheral nerve lesions with respect to their exact location, course, continuity, and extent in traumatic nerve lesions, and for assessing nerve entrapment and tumors. In this article, the authors discuss the basic technical considerations for using ultrasoniography in peripheral nerve assessment, and some of the clinical applications are illustrated.

• MR neurography (MRN) can aid the diagnosis of thoracic outlet syndrome (TOS). • Identifiable causes of TOS in MRN include fibrous bands and bony anomalies. • Increased T2W signal within brachial plexus elements indicate relevant nerve compression. • High positive predictive value allows confident and targeted indication for surgery.

Glucose deprivation strongly affected NP cell metabolism. The effects of an altered glucose supply on gene expression were more pronounced than the mechanically induced effects. Data in this study demonstrate that the glucose environment is more critical for disc cell metabolism than mechanical loads. In individual human donors, however, adequate mechanical stimuli might have a beneficial effect on matrix turnover during IVD degeneration.

obJective A pilot study of prophylactic nimodipine and hydroxyethyl starch treatment showed a beneficial effect on facial and cochlear nerve preservation following vestibular schwannoma (VS) surgery. A prospective Phase III trial was undertaken to confirm these results. methods An open-label, 2-arm, randomized parallel group and multicenter Phase III trial with blinded expert review was performed and included 112 patients who underwent VS surgery between January 2010 and February 2013 at 7 departments of neurosurgery to investigate the efficacy and safety of the prophylaxis. The surgery was performed after the patients were randomly assigned to one of 2 groups using online randomization. The treatment group (n = 56) received parenteral nimodipine (1-2 mg/hr) and hydroxyethyl starch (hematocrit 30%-35%) from the day before surgery until the 7th postoperative day. The control group (n = 56) was not treated prophylactically. results Intent-to-treat analysis showed no statistically significant effects of the treatment on either preservation of facial nerve function (35 [ ]) (p = 0.530) 12 months after surgery. Since tumor sizes were significantly larger in the treatment group than in the control group, logistic regression analysis was required. The risk for deterioration of facial nerve function was adjusted nearly the same in both groups ], p = 0.91). In contrast, the risk for postoperative hearing loss was adjusted 2 times lower in the treatment group compared with the control group (OR 0.49 [95% CI 0.18-1.30], p = 0.15). Apart from dosedependent hypotension (p < 0.001), no clinically relevant adverse reactions were observed. coNclusioNs There were no statistically significant effects of the treatment. Despite the width of the confidence intervals, the odds ratios may suggest but do not prove a clinically relevant effect of the safe study medication on the preservation of cochlear nerve function after VS surgery. Further study is needed before prophylactic nimodipine can be recommended in VS surgery.Clinical trial registration no.: 2009-012088-32 (www.clinicaltrialsregister.eu)

With intraoperative ultrasound, the extent of traumatic peripheral nerve lesions can be examined morphologically for the first time. It is a promising, noninvasive method that seems capable of assessing the type (intraneural/perineural) and grade of nerve fibrosis. Therefore, in combination with intraoperative neurophysiological studies, intraoperative high-resolution ultrasound may represent a major tool for noninvasive assessment of the regenerative potential of a nerve lesion.

Mammals differ in their regeneration potential after traumatic injury, which might be caused by species-specific regeneration programs. Here, we compared murine and human Schwann cell (SC) response to injury and developed an ex vivo injury model employing surgery-derived human sural nerves. Transcriptomic and lipid metabolism analysis of murine SCs following injury of sural nerves revealed down-regulation of lipogenic genes and regulator of lipid metabolism, including Pparg (peroxisome proliferator-activated receptor gamma) and S1P (sphingosine-1-phosphate). Human SCs failed to induce similar adaptations following ex vivo nerve injury. Pharmacological PPARg and S1P stimulation in mice resulted in up-regulation of lipid gene expression, suggesting a role in SCs switching towards a myelinating state. Altogether, our results suggest that murine SC switching towards a repair state is accompanied by transcriptome and lipidome adaptations, which are reduced in humans.