Nasal administration of mesenchymal stem cells reverses chemotherapy-induced peripheral neuropathy in mice

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequently reported adverse effects of cancer treatment. CIPN often persists long after treatment completion and has detrimental effects on patient’s quality of life. There are no efficacious FDA-approved drugs for CIPN. We recently demonstrated that nasal administration of mesenchymal stem cells (MSC) reverses the cognitive deficits induced by cisplatin in mice.Here we show that nasal administration of MSC after cisplatin- or paclitaxel treatment- completely reverses signs of established CIPN, including mechanical allodynia, spontaneous pain, and loss of intraepidermal nerve fibers (IENF) in the paw. The resolution of CIPN is associated with normalization of the cisplatin-induced decrease in mitochondrial bioenergetics in DRG neurons. Nasally administered MSC enter rapidly the meninges of the brain, spinal cord and peripheral lymph nodes to promote IL-10 production by macrophages.MSC-mediated resolution of mechanical allodynia, recovery of IENFs and restoration of DRG mitochondrial function critically depends on IL-10 production. MSC from IL-10 knockout animals are not capable of reversing the symptoms of CIPN. Moreover, WT MSC do not reverse CIPN in mice lacking IL-10 receptors on peripheral sensory neurons. In conclusion, only two nasal administrations of MSC fully reverse CIPN and the associated mitochondrial abnormalities via an IL-10 dependent pathway. Since MSC are already applied clinically, we propose that nasal MSC treatment could become a powerful treatment for the large group of patients suffering from neurotoxicities of cancer treatment.     

Sensory tricks in cervical dystonia correlate with enhanced brain activity during motor preparation

IntroductionAlthough sensory tricks are well known as the maneuvers that temporarily relieve dystonic symptoms in patients with cervical dystonia (CD), the underlying neurophysiological mechanisms remain unclear. We aimed to investigate brain potentials related to sensory tricks in patients with CD.MethodsThirteen patients with CD and 13 age-matched healthy volunteers participated. The experiment consisted of three conditions (moving the neck, moving an arm, and performing sensory tricks) presented in different blocks in random order in a contingent negative variation (CNV) paradigm. Warning and trigger stimuli (S1 and S2) were presented to the participants, who were instructed to prepare to perform the specific task for each condition after S1, and then to perform the task after S2. Early and late components of the CNV were measured.ResultsThe late CNVs in patients with CD were significantly larger than those in healthy participants in Fz, FCz, Cz, and C3 electrodes. Only in patients with CD, the late CNVs were significantly greater for the ‘sensory tricks’ condition compared to the ‘move neck’ condition in Fz and C3 electrodes.ConclusionThe late CNV is increased during sensory tricks in patients with CD, suggesting that sensory tricks may affect mechanisms related to the motor preparatory phase in the premotor and primary motor areas. Sensory tricks may normalize impaired motor preparation in dystonia, leading to improved dystonic symptoms.     

军校学员学习风格调查

目的探讨军校学员的学习风格。方法通过Myers-Briggs心理量表和感官偏爱测试表,调查某军校2010-2012年选修《时间管理与学习技巧》课程的所有学员的个性类型和感官偏爱等。结果军校学员的个性类型以内向为主,并呈逐年下降的趋势(χ2=7.320,P=0.026);2010年学员的感官偏爱主要是运动知觉,其次是听觉、阅读/写作、视觉,差别有统计学意义(χ2=12.400,P=0.006)。结论军校学员的个性类型以ISFJ(内向-直觉-情感-判断)为主,感官偏爱以运动知觉为主。掌握学员的学习风格,是科学有效的进行教学和学习的基础。     

Complexity of human postural control in subjects with unilateral peripheral vestibular hypofunction

Complexity is a new measure for identifying the adaptability of a complex system to meet possible challenges. For a center of pressure (COP) time series, the complexity measure represents the stability of postural control. In this study, multiscale entropy (MSE) was used to evaluate the complexity of COP time series in six test conditions of sensory organization test (SOT). Complexity index (CI) is defined as the summation of entropies with coarse-graining scales 1–20 by MSE. A total of 51 subjects belonging to 3 groups – healthy-young, healthy-elderly and dizzy – were recruited in this study. The COP signals in both anteroposterior (AP) and mediolateral (ML) directions were analyzed respectively. According to our results, the CI of AP-direction COP time series is significantly correlated to the equilibrium score, which represents the stability of postural control in SOT. The AP-direction sway is significant larger than the ML-direction sway, particularly in the test conditions with sway-surface. In additions, the CI of AP-direction COP for the healthy-elderly and dizzy groups are significantly lower than those for the healthy young group in the test conditions 1–4. The CI of ML-direction COP for the healthy-elderly group is significantly lower than those for the healthy-young and dizzy groups under test conditions 3 and 6. These results show that the complexity loss is a common status of AP-direction COP time series for both healthy-elderly and dizzy groups, and the complexity of ML-direction COP time series for subjects with unilateral vestibular dysfunction is higher than that for the healthy-elderly group specifically under test conditions 3 and 6.     

Control strategies for active lower extremity prosthetics and orthotics: a review

Technological advancements have led to the development of numerous wearable robotic devices for the physical assistance and restoration of human locomotion. While many challenges remain with respect to the mechanical design of such devices, it is at least equally challenging and important to develop strategies to control them in concert with the intentions of the user.This work reviews the state-of-the-art techniques for controlling portable active lower limb prosthetic and orthotic (P/O) devices in the context of locomotive activities of daily living (ADL), and considers how these can be interfaced with the user’s sensory-motor control system. This review underscores the practical challenges and opportunities associated with P/O control, which can be used to accelerate future developments in this field. Furthermore, this work provides a classification scheme for the comparison of the various control strategies.As a novel contribution, a general framework for the control of portable gait-assistance devices is proposed. This framework accounts for the physical and informatic interactions between the controller, the user, the environment, and the mechanical device itself. Such a treatment of P/Os – not as independent devices, but as actors within an ecosystem – is suggested to be necessary to structure the next generation of intelligent and multifunctional controllers.Each element of the proposed framework is discussed with respect to the role that it plays in the assistance of locomotion, along with how its states can be sensed as inputs to the controller. The reviewed controllers are shown to fit within different levels of a hierarchical scheme, which loosely resembles the structure and functionality of the nominal human central nervous system (CNS). Active and passive safety mechanisms are considered to be central aspects underlying all of P/O design and control, and are shown to be critical for regulatory approval of such devices for real-world use.The works discussed herein provide evidence that, while we are getting ever closer, significant challenges still exist for the development of controllers for portable powered P/O devices that can seamlessly integrate with the user’s neuromusculoskeletal system and are practical for use in locomotive ADL.     

带植入腓肠神经的游离骨间背皮瓣修复指腹皮肤缺损

目的探讨带植入腓肠神经的骨间背游离皮瓣修复指腹皮肤缺损,同时吻接植入神经重建指腹感觉功能的可行性。方法对11例(11指)指腹创面在未能带有前臂后侧皮神经的游离骨间背皮瓣皮下植入腓肠神经,然后移植修复指腹创面,同时吻接植入神经重建指腹感觉功能。结果 11例(11指)指腹创面均修复中皮瓣切取面积最小2 cm×1 cm,最大4 cm×3.8 cm。术后随访12~24个月,11例皮瓣均成活,感觉功能得到较好修复。结论带有植入腓肠神经的游离骨间背皮瓣既能修复指腹创面,同时吻接植入神经能重建指腹感觉功能,效果满意。     

Effects of Governor Vessel electroacupuncture on the systematic expressions of NTFs in spinal cord transected rats

This study evaluated the effects Governor Vessel electroacupuncture (GVEA) on the systematic regulation of neurotrophic factors (NTFs) in the spinal segments caudal (CSS) to the site of transection in rats subjected to spinal cord transection (SCT). Using RT-PCR, we amazingly found the gene expressions of NGF, IGF-1, FGF-2, CNTF, PDGF, TGF-β1, TrkA, TrkB and TrkC were downregulated following GVEA treatment. However, the number of GAP-43 and Synaptophysin profiles in the CSS in the GVEA rats showed a significant increase, compared with non-EA animals, although both the 5-HT and corticospinal fibers have no statistical differences in the CSS. Simultaneously, there was significant recovery in hindlimb locomotor and sensory functions after GVEA treatment. Therefore, these findings challenge the past view that GVEA promotes functional restoration, which is linking to the up-regulation of NTFs in rats subjected to SCT. The present findings may give some novel indication on the mechanism of acupuncture for the treatment of SCI.     

Neuroanatomy and neurochemistry of rat cornea: Changes with age

PurposeTo characterize the entire rat corneal nerve architecture, the changes that occur with aging, and its sensory, sympathetic, and parasympathetic fiber distribution.MethodsSprague-Dawley rats (aged 1 day to 2 years old) of both sexes were euthanized, and the whole corneas were immunostained with protein gene product 9.5 (PGP9.5). The specimens were double-labeled with antibodies against calcitonin gene-related peptide (CGRP) and substance P (SP) as sensory nerve markers, vasoactive intestinal peptide (VIP) as a parasympathetic nerve marker, and neuropeptide Y (NPY) and tyrosine hydroxylase (TH) as markers of sympathetic fibers. Relative nerve density positive for each antibody was assessed by computer-assisted image analysis.ResultsThick nerve trunks enter the cornea in the middle of the stroma and run towards the anterior stroma, subsequently dividing into smaller branches that penetrate upwards into the epithelium to form the subbasal nerve bundles. There was no significant difference in corneal innervation between sexes. CGRP and SP were the major sensory neuropeptides with 47.6% ± 3.5% and 34.9% ± 5.1%, respectively, of the total nerves. VIP was 18.4% ± 5.7%, and NPY and TH positive fibers took up 6.92% ± 2.66% and 2.92% ± 1.52%, respectively. Epithelial nerve density increased with age, reached full development at 5 weeks, and decreased at 120 weeks.ConclusionThis study provides a complete nerve architecture and content of components of sensory, parasympathetic, and sympathetic nerves in the rat cornea. The normal innervation pattern described here will provide an essential baseline for investigators who use the rat model for assessing corneal pathologies that involve nerve alterations.     

Compression du rameau superficiel du nerf radial par un kyste synovial du coude (À propos d’un cas et revue de littérature)

Compression of the radial nerve at the elbow is quite rare; entrapment of its superficial branch is exceptional. Extrinsic compression is the most frequent etiology. Magnetic resonance imaging plays a major role in the diagnosis, and early surgical excision or echoguided drainage – in case of synovial ganglion – allows a total recovery. The authors report the case of a compression of the superficial branch of radial nerve by an elbow synovial cyst treated by surgical resection.     

Schizophrenia-like neurophysiological abnormalities in 22q11.2 deletion syndrome and their association to COMT and PRODH genotypes

22q11.2 deletion syndrome (22q11.2DS) is a common genetic risk factor for the development of schizophrenia. We investigated two neurophysiological endophenotypes of schizophrenia – P50 sensory gating and mismatch negativity in 22q11.2DS subject and evaluated their association with catechol O-methyltransferase (COMT) and proline dehydrogenase (PRODH) genetic variants. We also assessed the association of neurophysiological measures with schizophrenia-like symptomatology in 22q11.2DS. Fifty-nine subjects, 41 with 22q11.2DS and 18 typically developing controls, participated in the study. The participants with 22q11.2DS were genotyped for the COMT Val¹⁵⁸Met (rs4680) and PRODH Gln¹⁹Pro (rs2008720) and Arg¹⁸⁵Trp (rs4819756) polymorphisms. Following psychiatric evaluation, all the participants underwent neurophysiological recordings and executive function assessment. The 22q11.2DS group showed poorer sensory gating of the P50 response than the controls. Within the 22q11.2DS group, the COMT Met allele was associated with poorer sensory gating, while both the COMT Met allele and the PRODH Pro-Arg haplotype were associated with smaller mismatch negativity amplitudes. Smaller mismatch negativity amplitudes predicted greater impairment of executive functions and greater severity of schizophrenia-like negative symptoms in 22q11.2DS. The current study demonstrates that sensory gating impairments that are typical of schizophrenia are found in 22q11.2DS subjects. Our results further suggest that COMT and PRODH genetic variations contribute to sensory gating and mismatch negativity schizophrenia-like impairments in 22q11.2DS, possibly via dopaminergic/glutamatergic networks. The associations of mismatch negativity impairments with increased severity of schizophrenia-like negative symptoms and poorer executive functions performance in our 22q11.2DS sample suggest that mismatch negativity is a potential endophenotype for schizophrenia in 22q11.2DS.