IRE1-Mediated Unfolded Protein Response Promotes the Replication of Tick-Borne Flaviviruses in a Virus and Cell-Type Dependent Manner.

Tick-borne flaviviruses (TBFV) can cause severe neurological complications in humans, but differences in tissue tropism and pathogenicity have been described for individual virus strains. Viral protein synthesis leads to the induction of the unfolded protein response (UPR) within infected cells. The IRE1 pathway has been hypothesized to support flavivirus replication by increasing protein and lipid biogenesis.

Ex vivo limb perfusion for traumatic amputation in military medicine.

Background: Limb loss has a drastic impact on a patient's life. Severe trauma to the extremities is common in current military conflicts. Among other aspects, "life before limb" damage control surgery hinders immediate replantation within the short post-traumatic timeframe, which is limited in part by the ischemic time for successful replantation.

Critical analysis of the value of the rabbit median nerve model for biomedical research on peripheral nerve grafts.

The rabbit has been proposed to represent an animal model that allows studying peripheral nerve regeneration across extended gap lengths. We describe here our experiences with the rabbit median nerve model and the obstacles it comes along with. This short communication is meant to inform the community and to prevent other researcher from investing time and animal lives in a model with low translational power.

Reprogramming of DNA methylation at NEUROD2-bound sequences during cortical neuron differentiation.

The characteristics of DNA methylation changes that occur during neurogenesis in vivo remain unknown. We used whole-genome bisulfite sequencing to quantitate DNA cytosine modifications in differentiating neurons and their progenitors isolated from mouse brain at the peak of embryonic neurogenesis. Localized DNA hypomethylation was much more common than hypermethylation and often occurred at putative enhancers within genes that were upregulated in neurons and encoded proteins crucial for neuronal differentiation.

Introduction: Thematic Papers Issue on Peripheral Nerve Regeneration and Repair.

Injuries to the peripheral nerves result in loss of motor, sensory and autonomic functions in the denervated segments of the body, thus having strong impact in the quality of life of affected patients. Neurons are able to regenerate their injured axons in the peripheral nerves; however, the endogenous repair mechanisms usually do not allow for a satisfactory functional recovery, especially after severe nerve injuries. The interest on regeneration after peripheral nerve injuries has increased in the recent years due to the numerous advances derived from studies of neurobiology, cell therapy, and tissue engineering.

Two-component collagen nerve guides support axonal regeneration in the rat peripheral nerve injury model.

Progress in material development has enabled the production of nerve guides that increasingly resemble the characteristics of an autologous nerve graft. In the present study, 20 mm adult rat sciatic nerve defects were bridged with the collagen-based, two-component nerve guide 'Neuromaix', the commercially available NeuraGen® nerve tube or an autologous nerve graft. Neuromaix was able to support structural as well as functional regeneration across this gap.

The Axon Guidance Protein Semaphorin 3A Is Increased in the Motor Cortex of Patients With Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disorder that leads to progressive paralysis of skeletal muscles and death by respiratory failure. There is increasing evidence that ALS is at least in part an axonopathy and that mechanisms regulating axonal degeneration and regeneration might be pathogenetically relevant. Semaphorin 3A (Sema3A) is an axon guidance protein; it acts as an axon repellent and prevents axonal regeneration.

Chitosan-film enhanced chitosan nerve guides for long-distance regeneration of peripheral nerves.

Biosynthetic nerve grafts are developed in order to complement or replace autologous nerve grafts for peripheral nerve reconstruction. Artificial nerve guides currently approved for clinical use are not widely applied in reconstructive surgery as they still have limitations especially when it comes to critical distance repair. Here we report a comprehensive analysis of fine-tuned chitosan nerve guides (CNGs) enhanced by introduction of a longitudinal chitosan film to reconstruct critical length 15 mm sciatic nerve defects in adult healthy Wistar or diabetic Goto-Kakizaki rats.

In vitro models for peripheral nerve regeneration.

The study of peripheral nerve repair and regeneration is particularly relevant in the light of the high clinical incidence of nerve lesions. However, the clinical outcome after nerve lesions is often far from satisfactory and the functional recovery is almost never complete. Therefore, a number of therapeutic approaches are being investigated, ranging from local delivery of trophic factors and other molecules to bioactive biomaterials and complex nerve prostheses.

Schwann cells overexpressing FGF-2 alone or combined with manual stimulation do not promote functional recovery after facial nerve injury.

Purpose: To determine whether transplantation of Schwann cells (SCs) overexpressing different isoforms of fibroblast growth factor 2 (FGF-2) combined with manual stimulation (MS) of vibrissal muscles improves recovery after facial nerve transection in adult rat.

Procedures: Transected facial nerves were entubulated with collagen alone or collagen plus naïve SCs or transfected SCs. Half of the rats received daily MS.

Gene therapy in peripheral nerve reconstruction approaches.

Gene transfer to a transected peripheral nerve or avulsed nerve root is discussed to be helpful where neurosurgical peripheral nerve reconstruction alone will not result in full recovery of function. Axonal regeneration is supposed to be facilitated by this new therapeutic approach via delivery of specific regeneration promoting molecules as well as survival proteins for the injured sensory and motor neurons. Therefore gene therapy aims in long-term and site-specific delivery of those neurotrophic factors.