Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.

Impulse magnetic stimulation facilitates synaptic regeneration in rats following sciatic nerve injury

The current studies describing magnetic stimulation for treatment of nervous system diseases mainly focus on transcranial magnetic stimulation and rarely focus on spinal cord magnetic stimulation. Spinal cord magnetic stimulation has been confirmed to promote neural plasticity after injuries of spinal cord, brain and peripheral nerve. To evaluate the effects of impulse magnetic stimulation of the spinal cord on peripheral nerve regneration, we compressed a 3 mm segment located in the middle third of the hip using a sterilized artery forceps to induce ischemia. Then, all animals underwent impulse magnetic stimulation of the lumbar portion of spinal crod and spinal nerve roots daily for 1 month. Electron microscopy results showed that in and below the injuryed segment, the inflammation and demyelination of neural tissue were alleviated, apoptotic cells were reduced, and injured Schwann cells and myelin fibers were repaired. These findings suggest that high-frequency impulse magnetic stimulation of spinal cord and corresponding spinal nerve roots promotes synaptic regeneration following sciatic nerve injury.

Ultrasonographic reference values for assessing normal radial nerve ultrasonography in the normal population

High-resolution ultrasound has been used recently to characterize median and ulnar nerves, but is seldom used to characterize radial nerves. The radial nerve is more frequently involved in en- trapment syndromes than the ulnar and median nerves. However, the reference standard for normal radial nerves has not been established. Thus, this study measured the cross-sectional areas of radial nerves of 200 healthy male or female volunteers, aged 18 to 75, using high-resolution ultrasound. The results showed that mean cross-sectional areas of radial nerves at 4 cm upon the lateral epicondyle of the humerus and mid-humerus （midpoint between the elbow crease and axilla） were 5.14± 1.24 and 5.08 ± 1.23 mm2, respectively. The age and the dominant side did not affect the results, but the above-mentioned cross-sectional areas were larger in males （5.31± 1.25 and 5.19 ±1.23 mm2） than in females （4.93 ± 1.21 and 4.93 ± 1.23 mm2, respectively）. In addition, the cross-sectional areas of radial nerves were positively correlated with height and weight （r = 0.38, 0.36, respectively, both P 〈 0.05）. These data provide basic clinical data for the use of high-resolution ultrasound for the future diagnosis, treatment, and prognostic evalua- tion of peripheral neuropathies.

Standard versus a novel technique for restoring neurological function following brachial plexus injuries

The brachial plexus, a complex network of peripheral nerves, involves the motor, sensory, and sympathetic nerve supply to the upper extremity, and is formed by the union of the ventral primary rami of the spinal nerves. Brachial plexus trauma, damage to the complex of nerves, has a high incidence from delivery throughout life, leading to loss of all innervation of the arm and hand, their paralysis, and frequently results in excruciating neuropathic pain. The most frequent brachial plexus repair techniques use autologous sensory nerve grafts to bridge the nerve gaps. However, these do not induce reliable neurological recovery or reduce neuropathic pain, thus permanent neurological loss and neuropathic pain frequently occur. The present study evaluated the current best brachial plexus repair techniques and another involving a collagen tube filled with autologous platelet-rich fibrin that clinically induces extensive neurological recovery and a reduction/elimination of neuropathic pain, which are not possible by sural nerve grafts, even across long nerve gaps that are repaired years post trauma, and in older patients. This novel technique is proposed for use in restoring brachial plexus neurological function and in reducing/eliminating neuropathic pain.

Cortical regulation of striatal projection neurons and interneurons in a Parkinson's disease rat model

Striatal neurons can be either projection neurons or interneurons, with each type exhibiting distinct susceptibility to various types of brain damage. In this study, 6-hydroxydopamine was injected into the right medial forebrain bundle to induce dopamine depletion, and/or ibotenic acid was injected into the M1 cortex to induce motor cortex lesions. Immunohistochemistry and western blot assay showed that dopaminergic depletion results in significant loss of striatal projection neurons marked by dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein, molecular weight 32 k Da, calbindin, and μ-opioid receptor, while cortical lesions reversed these pathological changes. After dopaminergic deletion, the number of neuropeptide Y-positive striatal interneurons markedly increased, which was also inhibited by cortical lesioning. No noticeable change in the number of parvalbumin-positive interneurons was found in 6-hydroxydopamine-treated rats. Striatal projection neurons and interneurons show different susceptibility to dopaminergic depletion. Further, cortical lesions inhibit striatal dysfunction and damage induced by 6-hydroxydopamine, which provides a new possibility for clinical treatment of Parkinson＇s disease.