Time course analysis of sensory axon regeneration in vivo by directly tracing regenerating axons

Most current studies quantify axon regeneration by immunostaining regeneration-associated proteins,representing indirect measurement of axon lengths from both sensory neurons in the dorsal root ganglia and motor neurons in the spinal cord.Our recently developed method of in vivo electroporation of plasmid DNA encoding for enhanced green fluorescent protein into adult sensory neurons in the dorsal root ganglia provides a way to directly and specifically measure regenerating sensory axon lengths in whole-mount nerves.A mouse model of sciatic nerve compression was established by squeezing the sciatic nerve with tweezers.Plasmid DNA carrying enhanced green fluorescent protein was transfected by ipsilateral dorsal root ganglion electroporation 2 or 3 days before injury.Fluorescence distribution of dorsal root or sciatic nerve was observed by confocal microscopy.At 12 and 18 hours,and 1,2,3,4,5,and 6 days of injury,lengths of regenerated axons after sciatic nerve compression were measured using green fluorescence images.Apoptosis-related protein caspase-3 expression in dorsal root ganglia was determined by western blot assay.We found that in vivo electroporation did not affect caspase-3 expression in dorsal root ganglia.Dorsal root ganglia and sciatic nerves were successfully removed and subjected to a rapid tissue clearing technique.Neuronal soma in dorsal root ganglia expressing enhanced green fluorescent protein or fluorescent dye-labeled microRNAs were imaged after tissue clearing.The results facilitate direct time course analysis of peripheral nerve axon regeneration.This study was approved by the Institutional Animal Care and Use Committee of Guilin Medical University,China(approval No.GLMC201503010)on March 7,2014.     

Dose response and time course of manganese-enhanced magnetic resonance imaging for visual pathway tracing in vivo

Axonal tracing is useful for detecting optic nerve injury and regeneration,but many commonly used methods cannot be used to observe axoplasmic flow and synaptic transmission in vivo.Manganese(Mn2+)-enhanced magnetic resonance imaging(MEMRI) can be used for in vivo longitudinal tracing of the visual pathway.Here,we explored the dose response and time course of an intravitreal injection of Mn Cl2 for tracing the visual pathway in rabbits in vivo using MEMRI.We found that 2 m M Mn Cl2 enhanced images of the optic nerve but not the lateral geniculate body or superior colliculus,whereas at all other doses tested(5–40 m M),images of the visual pathway from the retina to the contralateral superior colliculus were significantly enhanced.The images were brightest at 24 hours,and then decreased in brightness until the end of the experiment(7 days).No signal enhancement was observed in the visual cortex at any concentration of Mn Cl2.These results suggest that MEMRI is a viable method for temporospatial tracing of the visual pathway in vivo.Signal enhancement in MEMRI depends on the dose of Mn Cl2,and the strongest signals appear 24 hours after intravitreal injection.     

Alzheimer's beta-amyloid precursor protein is expressed on the surface of immediately ex vivo brain cells: A flow cytometric study

Beta-amyloid precursor protein (βAPP) is ubiquitously expressed, but deposition of the βAPP proteolytic fragment Aβ is virtually restricted to the brain, suggesting cell-specific processing of this molecule. Our laboratory has investigated expression of βAPP in mechanically dissociated, unfixed, immediately ex vivo cells from various mouse and rat organs by flow cytometry. Epitopes of predicted extracellular domains of βAPP recognized by the N-terminal 22C11 monoclonal antibody (mAb) and the juxtamembrane 4G8 mAb were not detectable on the surface of lymphoid cells, hepatocytes, or kidney cells. In contrast, surface 22C11 and 4G8 βAPP immunoreactivity was abundant on intact (propidium iodide-excluding) dissociated brain cells. The predicted C-terminal intracellular βAPP determinant recognized by the mAb Jonas was not detectable on the surface of intact brain cells, but was present in ethanol-permeabilized cells, consistent with a transmembrane configuration of βAPP in brain cells. Trypsinization of intact brain cells abolished cell surface immunoreactivity for 22C11, which was then reestablished by short-term culture. Augmentation of 22C11 and 4G8 surface immunoreactivity occurred when brain cells were cultured short-term in phenylarsine oxide, a general endocytosis inhibitor. By double staining protocols of brain cells with mAbs directed against βAPP ecto-domain epitopes and the neuronal surface proteins Thy-1 or neural cell adhesion molecule (NCAM), we observed that all Thy-1⁺ and NCAM⁺ cells (∼50%) were immunoreactive for surface βAPP, but that some βAPP⁺ cells (∼20%) were negative for these neuronal markers. Our data suggest that neurons and a subpopulation of other brain cells, unlike peripheral cells, can support βAPP as a type I intrinsic membrane molecule with an intact ectodomain, and that βAPP surface abundance is regulated by an equilibrium between membrane vesicle insertion and endocytotic internalization. Transmembrane βAPP holoprotein may be a critical determinant of brain-predominant processing of βAPP to Aβ, and may participate in a receptor/transducer function unique to brain cells. © 1996 Wiley-Liss, Inc.     

A method for specific transmitter identification of retrogradely labeled neurons: Immunofluorescence combined with fluorescence tracing

In the present article a method is described which allows the delineation of the projections of a single neuron as well as the identification of one or more of its chemical components. The technique is a combination of retrograde tracing and fluorescent dyes based on the work of Kuypers and collaborators and indirect immunofluorescence histochemistry as originally described by Coons and collaborators. The crucial parameters including the selection of the dyes, the injection technique and tissue processing as well as the appropriate immunohistochemical fluorescent markers and filter combinations are discussed. The method of choice involves the use of the retrogradely transported dyes Fast Blue, True Blue or Propidium Iodide, and in addition, for double labeling experiments, Diamidino Yellow or Primuline. They are combind with FITC (Propidium Iodide) or TRITC (Fast Blue, True Blue, Diamidino Yellow, Primuline) as immunofluorescence markers.     

Psychotherapy for compulsive buying disorder: A systematic review

Based on a literature review, the purpose is to identify the main therapeutic approaches for the compulsive buying disorder, a present time disorder characterized by excessive and uncontrollable concerns or behaviors related to buying or expenses, which may lead to adverse consequences. The systematic review was carried out by searching the electronic scientific bases Medline/Pubmed, ISI, PsycInfo. The search was comprised of full-text articles, written in Portuguese and English, with no time limit or restrictions on the type of study and sample. A total of 1659 references were found and, by the end, 23 articles were selected for this review. From the articles found, it was determined that, although there are case studies and clinical trials underlining the effectiveness of the treatment for compulsive buying, only those studies with a focus on the cognitive-behavioral therapy approach make evident the successful response to the treatment. The publication of new studies on the etiology and epidemiology of the disorder is necessary, in order to establish new forms of treatment and to verify the effectiveness and response of the Brazilian population to the existing protocols.     

Positive psychological interventions for neurological disorders: A systematic review

Objectives: Psychological well-being in people with neurological diseases can be compromised due to brain damage or psychological reactions towards chronic disabilities. This systematic review evaluated the efficacy of positive psychological intervention (PPI) in neurological populations. Methods: Previous studies relevant to this topic were identified by searches in PUBMED, EMBASE, MEDLINE, and PSYCINFO databases from Jan 1980 to August 2017. Results: Of 1361 articles identified, 31 studies were included. Nineteen studies were randomized controlled trials. Sixteen studies had sample sizes of less than 30. Twelve studies were rated as high quality using the National Heart, Lung, and Blood Institute (NHLBI) quality assessment tools. Six therapies were found: mindfulness-based approaches, positive savoring, life summary, expressive-based, hope-based interventions, and character strengths. These interventions were shown to improve quality of life, reduce symptomatic distress, and depressive symptoms. Conclusion: PPIs promote well-being among patients with neurological deficits. For PPIs to be considered as an evidence-based practice, more trials with adequate statistical power are required.     

Distance-delivered interventions for PTSD: A systematic review and meta-analysis

This systematic review and meta-analysis evaluated the efficacy of distance-delivered, guided approaches to treatment (e.g., delivered via telephone, Internet, mail, videoconferencing) for clinical and subclinical posttraumatic stress disorder (PTSD). A comprehensive search yielded 19 randomized controlled trials (1491 participants) to be included. Meta-analyses revealed that distance-delivered interventions led to significant within-group improvements in PTSD symptoms at post-treatment (g = 0.81, 95% CI 0.65 to 0.97) and 3–6 month follow-up (g = 0.78, 95% CI 0.59 to 0.97). Within-group depression and quality of life outcomes showed similar results, with medium post-treatment and follow-up effects. Compared to a waiting list, distance delivery (specifically, Internet treatments) led to superior PTSD outcomes (g = 0.68, 95% CI 0.51 to 0.86). Compared to face-to-face interventions, distance delivery (specifically, videoconferencing treatments) did not result in significantly different PTSD outcomes at post-treatment (g = −0.05, 95% CI −0.31 to 0.20) but led to inferior outcomes at 3–6 month follow-up (g = −0.25, 95% CI −0.44 to −0.07). Distance delivery of PTSD treatment is promising, but research is needed to determine its optimal use.     

Effectiveness of acupuncture for Parkinson's disease: A systematic review

The objective of this review is to assess the clinical evidence for or against acupuncture as a treatment for Parkinson's disease (PD). We searched the literature using 17 databases from their inception to September 2007 (searched again 3rd January 2008), without language restrictions. We included all randomized clinical trials (RCTs) regardless of their design. Methodological quality was assessed using the Jadad score. Eleven RCTs met all inclusion criteria. Three RCTs assessed the effectiveness of acupuncture on Unified Parkinson's Disease Rating Scale (UPDRS) compared with placebo acupuncture. A meta‐analysis of these studies showed no significant effect (n = 96, WMD, 5.7; 95% CI ?2.8 to 14.2, P = 0.19, heterogeneity: tau² = 0, χ² = 0.97, P = 0.62, I² = 0%). Another six RCTs compared acupuncture plus conventional drugs on improvement of symptoms of PD with drugs only. A meta‐analysis of two of these studies suggested a positive effect of scalp acupuncture (n = 106, RR, 1.46, 95% CI = 1.15 to 1.87, P = 0.002; heterogeneity: tau² = 0.00, χ² = 1.14, P = 0.29, I² = 12%). Two further RCTs tested acupuncture versus no treatment. The meta‐analysis of these studies also suggested beneficial effects of acupuncture. The results of the latter two types of RCTs fail to adequately control for nonspecific effects. In conclusion, the evidence for the effectiveness of acupuncture for treating PD is not convincing. The number and quality of trials as well as their total sample size are too low to draw any firm conclusion. Further rigorous trials are warranted. © 2008 Movement Disorder Society     

硅凝胶膜治疗病理性瘢痕的系统评价

背景：评价硅凝胶膜治疗病理性瘢痕的有效性及安全性。 资料来源：计算机检索Cochrane图书馆临床对照试验数据库(Cochrane Central Register of Controlled Trials, 2009年第3期)、 MEDLINE光盘数据库(1966/2009-09)、EMBASE光盘数据库(1984/2009-09)、中国生物医学文献数据库(CBM, 1979/2009-09)、维普中文数据库(VIP, 1989/2009-09)、中国期刊全文数据库(CNKI, 1979/2009-09)及所获文献的参考文献。 资料选择：筛选所有应用硅凝胶膜治疗病理性瘢痕,对照组为空白或其他治疗的随机、半随机对照试验及临床对照试验,使用Cochrane协作网提供的RevMan4.2.10软件对纳入文献进行统计分析。 结局评价指标：主要指标为瘢痕大小,次要指标包括瘢痕颜色、弹性或质地,患者对外观的主观评价,痛、痒等临床症状改善情况,症状改善时间等。 结果：硅凝胶膜在改善瘢痕弹性、颜色、患者主观评价方面优于空白对照组,差异有显著性意义(RR弹性=8.60,95%CI 2.55~29.02),(RR颜色=21.33,95%CI 4.33~104.99),(RR患者主观评价=32.33,95% CI 6.63~157.59)。硅凝胶膜不良反应一般较轻,易缓解。 结论：硅凝胶膜在改善病理性瘢痕颜色、弹性及患者主观评价方面可能具有一定的疗效,但硅凝胶在改善瘢痕大小方面并无显著疗效。硅凝胶膜并不优于其他治疗方法。可以认为硅凝胶膜治疗病理性瘢痕是安全的。由于纳入的研究质量均低,结果具有高度的偏倚性。 关键词：硅凝胶膜;病理性瘢痕;系统评价     

Deep brain stimulation for essential tremor: A systematic review

Deep brain stimulation (DBS) is a neurosurgical treatment, which has proven useful in treating Parkinson's disease. This systematic review assessed the safety and effectiveness of DBS for another movement disorder, essential tremor. All studies concerning the use of DBS in patients with essential tremor were identified through searching of electronic databases and hand searching of reference lists. Studies were categorized as before/after DBS or DBS stimulation on/off to allow the effect of the stimulation to be analyzed separately to that of the surgery itself. A total of 430 patients who had received DBS for essential tremor were identified. Most of the reported adverse events were mild and could be treated through changing the stimulation settings. Generally, in all studies, there was a significant improvement in outcomes after DBS compared with baseline scores. In addition, DBS was significantly better in testing when the stimulation was turned on, compared with stimulation turned off or baseline. Based on Level IV evidence, DBS is possibly a safe and effective therapy for essential tremor. © 2010 Movement Disorders Society     

Awareness of deficit following traumatic brain injury: A systematic review of current methods of assessment

ABSTRACT

Background: Awareness of deficit plays an important role in adjustment following a brain injury and has been noted to impact on engagement with and outcome of rehabilitation. However, there are challenges associated with the assessment of awareness.

Aim: To systematically review all instruments used to assess intellectual awareness of deficits following Traumatic Brain Injury (TBI) in adults, and evaluate instrument characteristics (e.g., the format and focus of measures of awareness) and assessment methods adopted.

Results: Thirty-four studies, all rated as fair to good quality, were identified and within these twenty-three different assessment tools were adopted. The most common method of assessment was patient-proxy discrepancy, with three frequently used instruments employed in a total of 22 of the 34 studies. Across studies, variability was noted regarding the type of assessment method dependent on various sample demographics (e.g., age of sample) and injury characteristics (e.g., time post injury).

Conclusions: There is no consensus on the preferred instrument to assess intellectual awareness of deficits after TBI. Continued instrument development should attempt to incorporate multiple perspectives and assessment should take into account demographic and injury-related factors. An insightful avenue for future research would be to determine which factors are likely to impact awareness measurement.     

Anatomical evidence for direct fiber projections from the cerebellar nucleus interpositus to rubrospinal neurons. A quantitative EM study in the rat combining anterograde and retrograde intra-axonal tracing methods

A quantitative electron microscopic (EM) study combining the anterograde intra-axonal transport of radioactive amino acids and the retrograde intra-axonal transport of the enzyme horseradish peroxidase (HRP) was performed in the magnocellular red nucleus of the rat to obtain anatomical evidence as to whether there is a direct projection from the cerebellar nucleus interpositus to the cells in the red nucleus that give rise to the rubrospinal tract. Large asymmetrical synaptic terminals were radioactively labeled in the magnocellular red nucleus following injections of [3H]leucine into the cerebellar nucleus interpositus. In these same animals, the postsynaptic target neurons were labeled with HRP granules after injection of this substance in the rubrospinal tract. A quantitative analysis showed that more than 85% of the large and giant neurons in the magnocellular red nucleus were labeled with HRP granules and also received synaptic contacts from radioactively-labeled terminals. Thus, it can be concluded that in the rat, afferents from the cerebellar nucleus interpositus establish asymmetrical synaptic contacts with large and giant rubrospinal neurons, thus confirming and extending the previous physiological evidence of such direct monosynaptic connections.     

Multidisciplinary rehabilitation for children with brain tumors: A systematic review

Background: There is an increasing need to assess the evidence of a multidisciplinary approach for both short-term and long-term management of neurological sequelae arising from the diagnosis and treatment of brain tumors in childhood. Methods: We performed a systematic review of the evidence base for multidisciplinary paediatric brain tumor rehabilitation using seven databases. PRISMA guidelines were adhered to and the review was registered with the PROSPERO international prospective register of systematic reviews (registration number CRD42014015070). Results: The literature search identified 3,061 results. Three service evaluations were included. The review identified limited evidence in favor of multidisciplinary rehabilitation for children with brain tumors. Due to the lack of controlled trial data and heterogeneity of the interventions and outcome measures, no meta-analysis could be performed. Conclusions: Studies utilising a coordinated multi-centre approach with standardized outcome measures are recommended in order to enable robust assessment of the efficacy of multidisciplinary rehabilitation services.     

Efficacy of ketogenic diet for infantile spasms: A systematic review

The aim of this systematic review was to collect and analyze all the RCTs and observational studies investigating the efficacy of ketogenic diet (KD) in infantile spasms (IS) patients after a 1‐ to 6‐month follow‐up period, in terms of decrease in seizure frequency of >50% or a seizure‐free interval. Moreover, the potential effect of gender, IS etiology, age at onset of IS, and age at start of KD have been investigated. Finally, we evaluated the seizure‐free rate at 12 and 24 months of follow‐up. In June 2016, a computer search was performed on MedLine (PubMed), EMBASE, and the Cochrane Library. Only, English language studies conducted after 1980 and those reporting in detail the variation in seizure frequency have been selected. Thirteen observational studies (341 patients) were included in the final analysis. A median rate of 64.7% of patients experienced a spasm reduction >50% (IQR: 38.94%). The median spasm‐free rate was 34.61% (IQR: 37.94%). IS of unknown etiology seemed to have an increased probability of achieving freedom from seizures (RR: 1.72, 95%CI: 1.18‐2.53). Long‐time follow‐up data revealed a median seizure‐free rate of 9.54% (IQR: 18.23%). Although the literature is still lacking in high‐quality studies, which could provide a stronger level evidence, our findings suggest a potential benefit of KD for drug‐resistant IS patients.     

Pyridoxine,folate and cobalamin for migraine: A systematic review

There is a possible relationship between migraine and hypercoagulability inducing factors, such as hyperhomocysteinemia. In this context, homocysteine (Hcy)-lowering vitamins (B6-folate-B12) may prove beneficial in the management—prophylaxis of migraine. We performed a systematic literature search in order to retrieve studies assessing the supplementation of B6, folate and B12 (alone or as adjunctive therapies) to migraine patients, as well as patients suffering from other primary headache disorders. MEDLINE, EMBASE, CENTRAL, Google Scholar, trial registries and OpenGrey were searched. Twelve relevant articles were retrieved. The management of acute migraine attacks with Hcy-lowering vitamins has not provided promising results (one randomized controlled trial—RCT—and one prospective uncontrolled trial). On the contrary, significant benefits were registered for the use of B6 alone, in combination with folate and in combination with folate and B12 in the prophylaxis of migraine with aura (MA) in adults compared to placebo (five RCTs, only one did not obtain significant results). Folate supplementation alone was not more efficacious than placebo (one RCT). Limited data for the prophylaxis of migraine without aura (MO) in children (two prospective uncontrolled trials) and adults (two prospective uncontrolled trials involving both MA and MO participants) impede the extraction of safe conclusions. An overall attractive safety profile was exhibited with gastrointestinal adverse events being the most common. Overall, a potential beneficial effect regarding the administration of B6, folate and/or B12 in the prophylaxis of MA in adults was indicated. Additional high-quality RCTs that will investigate MO in adults as well as MO and MA in children are warranted.