关键词： AAV   ALS   HGF   Sciatic nerve crush   IM injection  

摘要： Hepatocyte growth factor (HGF) is a versatile neurotrophic factor that mediates a variety of cellular activities. In this study, we investigated the effects of intramuscularly injected recombinant AAV vectors expressing HGF in two pathologic conditions: the sciatic nerve crush and the SOD1-G93A transgenic mouse models. AAV serotype 6 (rAAV6) was chosen based on its expression levels in, and capability of moving to, the spinal cord from the injected muscle area. In the nerve crush model, rAAV6-HGF was shown to reduce the degree of mechanical allodynia, increase the cross-sectional area of muscle fibers, promote regrowth of peripheral axons, and improve motor functions. In the SOD1-G93A TG mouse model, rAAV6-HGF increased the mass of the tibialis anterior and gastrocnemius, alleviated disease symptoms, and prolonged survival. Improvements in integrity and functions of muscle in these models seemed to have come from the ability of HGF produced from rAAV6-HGF to regulate the expression of various atrogenes through the control of the FOXO signaling pathway. Our findings suggested that intramuscular injection of rAAV6-HGF might be used to relieve various symptoms associated with muscle atrophy and/or nerve damages observed in a majority of neuromuscular diseases. (C) 2019 The Authors. Published by Elsevier Inc.

关键词： meta-analysis   outcome assessment   spinal cord injuries   spinal fusion   surgical decompression  

摘要： The impact of surgical timing in neurological recovery in thoracic and thoracolumbar traumatic spinal cord injury (tSCI) is still a subject of discussion. While in cervical tSCI one may expect a beneficial effect of early intervention within 24 h, especially in complete cases, this has not yet been demonstrated clearly for thoracic tSCI. This study addresses neurological improvement after early and late surgery for thoracic and thoracolumbar tSCI. A systematic search retrieved 14 publications of observational studies reporting outcome measurements after surgery in 1075 patients with thoracic and thoracolumbar tSCI from PubMed and Embase databases. Surgery was considered early within 24 h and late thereafter. An improvement of at least one and two grades on the American Spinal Injury Association Impairment Scale (ASIA) was evaluated. The Meta-Analyses and Systematic Reviews of Observational Studies guidelines were followed. Improvement rates were summarized using individual patient data in a Bayesian random effects model and compared for those with early and late surgery. In the qualitative analysis, six of seven studies, which investigated the effect of surgical timing, observed a significant effect of early surgery on at least one ASIA grade improvement. Quantitative analysis in 948 patients with thoracic and thoracolumbar tSCI data, however, did not reveal a significant increase in odds of >= 1 ASIA grade recovery in early surgery (66.8% [95% confidence interval (CI): 45.0-87.8%] compared with late surgery (48.9% [95% CI: 25.1-70.7%;odds ratio (OR) 2.2 (95% CI: 0.6-14.0]). This study did not observe a significant beneficial effect of surgical decompression within 24 h in patients with thoracic and thoracolumbar tSCI.

关键词： Transcranial direct-current stimulation   Gait   Rehabilitation   Neurological disorder  

摘要： Background Transcranial direct-current stimulation (tDCS) is an easy-to-apply, cheap, and safe technique capable of affecting cortical brain activity. However, its effectiveness has not been proven for many clinical applications. Objective The aim of this systematic review was to determine whether the effect of different strategies for gait training in patients with neurological disorders can be enhanced by the combined application of tDCS compared to sham stimulation. Additionally, we attempted to record and analyze tDCS parameters to optimize its efficacy. Methods A search in Pubmed, PEDro, and Cochrane databases was performed to find randomized clinical trials that combined tDCS with gait training. A chronological filter from 2010 to 2018 was applied and only studies with variables that quantified the gait function were included. Results A total of 274 studies were found, of which 25 met the inclusion criteria. Of them, 17 were rejected based on exclusion criteria. Finally, 8 trials were evaluated that included 91 subjects with stroke, 57 suffering from Parkinson's disease, and 39 with spinal cord injury. Four of the eight assessed studies did not report improved outcomes for any of its variables compared to the placebo treatment. Conclusions There are no conclusive results that confirm that tDCS can enhance the effect of the different strategies for gait training. Further research for specific pathologies, with larger sample sizes and adequate follow-up periods, are required to optimize the existing protocols for applying tDCS.

关键词： circular RNA TLK1   miR-335   neuronal injury   stroke   TIPARP  

摘要： Circular RNAs (circRNAs) are expressed at high levels in the brain and are involved in various CNS diseases. However, the potential role of circRNAs in ischemic stroke-associated neuronal injury remains largely unknown. Here, we investigated the important functions of circRNA TLK1 (circTLK1) in this process. The levels of circTLK1 were significantly increased in brain tissues in a mouse model of focal cerebral ischemia and reperfusion. Knockdown of circTLK1 significantly decreased infarct volumes, attenuated neuronal injury, and improved neurological deficits. Furthermore, circTLK1 functioned as an endogenous miR-335-3p sponge to inhibit miR-335-3p activity, resulting in the increase of 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible poly (ADP-ribose) polymerase expression and a subsequent exacerbation of neuronal injury. Clinical studies confirmed increased levels of circTLK1 in the plasma of patients with acute ischemic stroke (59 males and 12 females). Our findings reveal a detrimental role of circTLK1 in ischemic brain injury.

关键词： Rickettsia raoultii   Neurological abnormalities   Northwestern China  

摘要： Background The number of new rickettsial species are rapidly increasing, and increasing numbers of Rickettsia raoultii (R. raoultii) infection cases have been detected in humans. However, neurological abnormalities caused by R. raoultii are rarely reported, especially in northwestern China. Case presentation A 36-year-old Kazakh shepherd with an attached tick on part temporalis, presented with right eyelid droop, lethargy, fever, headache, fever (38.0-41.0 degrees C) and erythematous rash. The examination of cerebrospinal fluid (CSF) showed cerebrospinal pressure of 200 mm H2O, leukocyte count of 300.0 x 10(6)/L, adenosine deaminase of 2.15 U/L, and total protein concentration of 0.93 g/L. The diagnosis of R. raoultii infection was confirmed by six genetic markers, and semi-quantified by enzyme-linked immunosorbent assay for rickettsial antigen. The patient gradually recovered after treatment with doxycycline and ceftriaxone. R. raoultii DNA was found both in a tick detached from this patient and in 0.18% (2/1107) of blood samples collected from local shepherds. Conclusions This is the first reported case with neurological abnormalities caused by R. raoultii in northwestern China. It is vital to detect rickettsial agents both in blood and CSF for tick bite patients with neurological abnormalities. Public health workers and physicians should pay attention to neurological abnormalities caused by Rickettsia.

关键词： Glycolipid   Glycan   Anti-ganglioside IgG-antibodies   Autoimmunity   Neurological disorder   IgG   IgM discordance  

摘要： Background Different neurological disorders frequently display antibodies against several self-glycans. Increasing evidence supports their pathogenic role;however, far less is known about their origin. Meanwhile, antibodies recognizing non-self glycans appear in normal human serum during immune response to bacteria. Methods Using high performance thin layer chromatography-immunostaining, we comparatively evaluated humoral immune response (IgG and IgM immunoreactivity) against glycolipids carrying self-glycans (GM3/GM2/GM1/GD1a/GD1b/GD3/GT1b/GQ1b) and non-self glycans (Forssman/GA1/"A" blood group/Nt7) in sera from 383 patients with neurological disorders along with 87 healthy controls. Results In contrast to no healthy controls having anti-self glycan IgG antibodies, one-fifth of patients' sera had anti-self glycan IgG antibodies: remarkably, 60% of these occurred without IgM antibodies of the same specificity. Contrary to this unusual fact (anti-self glycan IgG occurrence without simultaneous presence of IgM having the same specificity similar to IgG/IgM discordance), all IgG antibodies against non-self glycans occurred simultaneously with their IgM antibody counterpart (i.e. 0% discordance). When analyzed closer, the IgG/IgM discordance frequency for anti-self glycans exhibited a dual trend: below 40% for IgG antibodies against GM2, GM1 and GD1b, and greater than 53% for IgG antibodies against the remaining self glycans. Interestingly, this discordance behavior was common to several different neurological disorders. Conclusions Classic immunology principles indicate this anti-self glycan IgG/IgM discordance should not occur in an antibody response;its unusual presence is discussed within the "binding site drift hypothesis" context, where anti-self glycan IgG antibodies could originate from pre-existing IgG recognizing structurally-related non-self glycans.

关键词： docosahexaenoic acid   functional improvement   lipid mediator profile   neuroprotection   traumatic brain injury  

摘要： Traumatic brain injury (TBI) can lead to life-changing neurological deficits, which reflect the fast-evolving secondary injury post-trauma. There is a need for acute protective interventions, and the aim of this study was to explore in an experimental TBI model the neuroprotective potential of a single bolus of a neuroactive omega-3 fatty acid, docosahexaenoic acid (DHA), administered in a time window feasible for emergency services. Adult mice received a controlled cortical impact injury (CCI) and neurological impairment was assessed with the modified Neurological Severity Score (mNSS) up to 28 days post-injury. DHA (500 nmol/kg) or saline were injected intravenously at 30 min post-injury. The lipid mediator profile was assessed in the injured hemisphere at 3 h post-CCI. After completion of behavioral tests and lesion assessment using magnetic resonance imaging, over 7 days or 28 days post-TBI, the tissue was analyzed by immunohistochemistry. The single DHA bolus significantly reduced the injury-induced neurological deficit and increased pro-resolving mediators in the injured brain. DHA significantly reduced lesion size, the microglia and astrocytic reaction, and oxidation, and decreased the accumulation of beta-amyloid precursor protein (APP), indicating a reduced axonal injury at 7 days post-TBI. DHA reduced the neurofilament light levels in plasma at 28 days. Therefore, an acute single bolus of DHA post-TBI, in a time window relevant for acute emergency intervention, can induce a long-lasting and significant improvement in neurological outcome, and this is accompanied by a marked upregulation of neuroprotective mediators, including the DHA-derived resolvins and protectins.

摘要： The SVZ contains neural stem cells and transits amplifying cells, microglia, ependyma, neuroblasts, and astrocytes. [...]identifying the cells that are proliferating and determining whether this is a cell autonomous effect is important. Alternatively, enlarged neurons or astrocytes could potentially lead to megalencephaly and hydrocephalus. [...]determining the exact cause of death will be important to provide mechanistic insight into how AAV9-TSC1 rescue is exerted. Mutations that result in dominant negative function could alter tuberin or Rheb, and it is unclear whether AAV-delivered hamartin could compensate. [...]successful clinical trials would need to carefully choose patient cohorts with TSC1 mutations.

关键词： Metastatic spine tumor   Epidural spinal cord compression   Paralysis   Radiotherapy   Surgery  

摘要： Background Therapeutic intervention has recently been actively performed for metastatic spine tumor even though spinal cord paralysis is not clearly observed, but there has been no report in which the degree of spinal cord compression by tumor was taken into consideration for the paralysis-preventing effect of treatment. Thus, we investigated the neurological outcome after treatment of patients with spinal cord compression in a state of impending paralysis. Methods A retrospective cohort study. The subjects were 88 patients with epidural spinal cord compression (ESCC) scale 1b or severer compression with American Spinal Injury Association (ASIA) E spinal metastasis. The neurological outcome after the therapeutic intervention was investigated at regular intervals until death. The therapeutic intervention was posterior decompression and stabilization in 18 patients, stabilization without posterior decompression in 15, and radiotherapy in 55 patients (3 groups). Results The ASIA aggravation group was comprised of 15 patients, and the severity of paralysis was ASIA A in 3, B in 3, C in 6, and D in 3. Paralysis appeared in 16.7% in the posterior decompression and stabilization group, 13.3% in the posterior stabilization without decompression group, and 18.8% in the radiotherapy group. In the transverse view, the incidence was high in cases with advancement to the intervertebral foramen and circumferential-type advancement, and paralysis developed in more than 20% of ESCC 1c or severer cases. Factors influencing neurological aggravation were investigated, but there was no significant factor. Conclusion In ESCC 1b or severer cases with ASIA E spinal metastasis, paralysis aggravated after therapeutic intervention in 16.7% in the posterior decompression and stabilization group, 13.3% in the stabilization without decompression group, and 16.7% in the radiotherapy group. There was no significant factor influencing the development of paralysis.