Biophysical stimulation induces demyelination via an integrin-dependent mechanism.

ObjectiveChronic nerve compression (CNC) injuries occur when peripheral nerves are subjected to sustained mechanical forces, with increasing evidence implicating Schwann cells as key mediators. Integrins, a family of transmembrane adhesion molecules that are capable of intracellular signaling, have been implicated in a variety of biological processes such as myelination and nerve regeneration. In this study, we seek to define the physical stimuli mediating demyelination and to determine whether integrin plays a role in the demyelinating response.MethodsWe used a previously described in vitro model of CNC injury where myelinating neuron-Schwann cell cocultures were subjected to independent manipulations of hydrostatic pressure, hypoxia, and glucose deprivation in a custom bioreactor. We assessed whether demyelination increased in response to applied manipulation and determined whether integrin-associated signaling cascades are upregulated.ResultsBiophysical stimulation of neural tissue induced demyelination and Schwann cell proliferation without neuronal or glial cytotoxicity or apoptosis. Although glucose deprivation and hypoxia independently had minor effects on myelin stability, together they potentiated the demyelinating effects of hydrostatic compression, and in combination, significantly destabilized myelin. Biophysical stimuli transiently increased phosphorylation of the integrin-associated tyrosine kinase Src within Schwann cells. Silencing this integrin signaling cascade blocked Src activation and prevented pressure-induced demyelination. Colocalization analysis indicated that Src is localized within Schwann cells.InterpretationThese results indicate that myelin is sensitive to CNC injury and support the novel concept that myelinating cocultures respond directly to mechanical loading via activating an integrin signaling cascade

Establishing validity of the fundamentals of spinal surgery (FOSS) simulator as a teaching tool for orthopedic and neurosurgical trainees

Pedicle screw placement is a demanding surgical skill as a spine surgeon can face challenges including variations in pedicle morphology and spinal deformities. Available CT simulators for spine pedicle placement can be very costly and hands-on cadaver courses are limited by specimen availability and are not readily accessible. To conduct validation of a simulated training device for essential spine surgery skills. Cross-sectional, empirical study of physician performance on a surgical simulator model. Spine attending physicians and residents from four different academic institutions across the United States. Performance metrics on two surgical simulator tasks. After IRB approval, an inexpensive ($30) simulator was developed to test two main psychomotor tasks (1) creation of the pedicle screw path with a standard gearshift probe without cortical breaks and (2) the ability to palpate for the presence or absence of cortical breaches as well as determine the location of wall defects. Orthopedic and neurosurgery residents (N=72) as well as spine attending surgeons (N=26) participated from four different institutions. To test construct validity, performance metrics were compared between participants of different training status through one-way analysis of variance and linear regression analysis, with significance set at p<.05. Spine attending surgeons consistently scored higher than the residents, in the screw trajectory task with triangular base (p=.0027) and defect probing task (p=.0035). In defect probing, performance improved with linear trend by number of residency training years with approaching significance (p=.0721). In that task, independent of institutional affiliation, PGY-2 residents correctly identified an average of 1.25±0.43 fewer locations compared with attending physicians (p=.0049). More than 80% of the spine attendings reported they would use the simulator for training purposes. This low-cost fundamentals of spine surgery simulator detected differences in performances between spine attending surgeons and surgical residents. Programs should consider implementing a simulator such as fundamentals of spine surgery to assess and develop pedicle screw placement ability outside of the operating room