In the spinal cord, neurons and glial cells actively interact and contribute to neurofunction. Surprisingly, both cell types have similar receptors, transporters and ion channels and also produce similar neurotransmitters and cytokines. The neuroanatomical and neurochemical similarities work synergistically to maintain physiological homeostasis in the normal spinal cord. However, in trauma or disease states, spinal glia become activated, dorsal horn neurons become hyperexcitable contributing to sensitized neuronal-glial circuits. The maladaptive spinal circuits directly affect synaptic excitability, including activation of intracellular downstream cascades that result in enhanced evoked and spontaneous activity in dorsal horn neurons with the result that abnormal pain syndromes develop. Recent literature reported that spinal cord injury produces glial activation in the dorsal horn; however, the majority of glial activation studies after SCI have focused on transient and/or acute time points, from a few hours to one month, and peri-lesion sites, a few millimeters rostral and caudal to the lesion site. In addition, thoracic spinal cord injury produces activation of astrocytes and microglia that contributes to dorsal horn neuronal hyperexcitability and central neuropathic pain in above-level, at-level and below-level segments remote from the lesion in the spinal cord. The cellular and molecular events of glial activation are not a simple event, rather it is the consequence of a combination of several neurochemical and neurophysiological changes following SCI. The ionic imbalances, neuroinflammation and alterations of cell cycle proteins after SCI are predominant components for neuroanatomical and neurochemical changes that result in glial activation. More importantly, SCI induced release of glutamate, proinfloammatory cytokines, ATP, reactive oxygen species (ROS) and neurotrophic factors trigger activation of postsynaptic neurons and glial cells via their own receptors and channels that, in turn, contribute to neuronal-neuronal and neuronal-glial interaction as well as microglia-astrocytic interactions. However, a systematic review of temporal and spatial glial activation following SCI has not been done. In this review, we describe time and regional dependence of glial activation and describe activation mechanisms in various SCI models in rats. These data are placed in the broader context of glial activation mechanisms and chronic pain states. Our work in the context of work by others in SCI models demonstrate that dysfunctional glia, a condition called “gliopathy”, are key contributors in the underlying cellular mechanisms contributing to neuropathic pain.

Object. The use of polymethylmethacrylate (PMMA) cement by percutaneous injection in cases requiring vertebroplasty provides pain relief in the treatment of osteoporotic vertebral compression fractures. A retrospective study was performed to assess what caused PMMA cement to leak into the epidural space and to determine if this leakage caused any changes in its therapeutic benefits. Methods. Polymethylmethacrylate was injected into 347 vertebral compression fractures in 159 patients. The cement leaked into the epidural space in 92 (26.5%) of 347 treated vertebrae in 64 (40.3%) of the 159 patients, as demonstrated on postoperative computerized tomography scanning. Epidural leakage of PMMA cement occurred more often when injected above the level of T-7 (p = 0.001) than below. The larger the volume of PMMA injected the higher the incidence of epidural leakage (p = 0.03). Using an injector also increased epidural leakage (p = 0.045). The position of the needle tip within the vertebral body and the pattern of venous drainage did not affect epidural leakage of the cement. Leakage of PMMA into the epidural space reduced the pain relief expected after vertebroplasty. The immediate postoperative visual analog scale scores were higher (and therefore reflective of less pain relief) in patients in whom epidural PMMA leakage occurred (p = 0.009). Three months postoperatively, the authors found the highest number of patients presenting with pain relief, including those in the group with epidural leakage, and at this follow-up stage there were no significant differences between the two groups. Conclusions. The authors found that epidural leakage of PMMA after percutaneous vertebroplasty was dose dependent. The larger amount of injected PMMA, the higher the incidence of leakage. Injecting vertebral levels above T-7 also increased the incidence of epidural leakage. Epidural leakage of PMMA may attenuate only the immediate therapeutic effects of vertebroplasty.

The effects of guava leaves extracted using solvents of water, ethanol, methanol, and different concentrations of hydroethanolic solvents on phenolic compounds and flavonoids, and antioxidant properties have been investigated. The antioxidant capability was assessed based on 2,2-diphenyl-1-picrylhydrazyl radical and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging abilities, reducing power, and nitric oxide-and nitrate-scavenging activities. The results demonstrated that the antioxidant ability of guava leaf extracts has a strong relationship with phenolic compound content rather than flavonoid content. Phenolic compound content of water extracted guava leaves was higher compared to pure ethanol and methanol extracts. However, phenolic compound content extracted using hydroethanolic solvent was higher than water, whereas 50% hydroethanolic was observed to be the most effective solvent showing high antioxidant ability.

Ventricular CSF shunting surgery has changed the overall outcome figures for hydrocephalic patients over the past three decades. The factors that have improved the outcome are evolution of the shunt systems, improvement of the surgical environment and use of potent antibiotics, technological advances in brain imaging, and refinements in the assessment of cognitive and functional outcomes and of actuarial statistical techniques. But the recent large studies revealed that nearly half of all shunt placements were for revision, and there is a low but real percentage of cases in which death and neurological impairment are related to shunt surgery. The most frequent complication was shunt obstruction, followed by infection, disconnection, hematoma and slit ventricle syndrome. This clearly means that the shunt systems and the techniques in current use involve many problems that have yet to be solved. To solve these problems, new shunt systems should be developed and continuous efforts at reducing shunt infection should be made. The overall complication rate in the authors' series was 31.7%, but we have been able to reduce the complication rate from 37% to 25% by exercising special care focused on the surgical environment and techniques. Careful, long-term follow-up using various parameters and proper statistical analysis is another important factor in improving surgical outcome. Multicenter and international studies will be easier with the development of a network, and it will give us a strong background to treat hydrocephalus.

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A phosphorothioate single-stranded DNA aptamer (thioaptamer) targeting transforming growth factor-β1 (TGF-β1) was isolated by in vitro combinatorial selection. The aptamer selection procedure was designed to modify the backbone of single-stranded DNA aptamers, where 5′ of both A and C are phosphorothioates since this provides enhanced nuclease resistance as well as higher affinity than that of a phosphate counterpart. The thioaptamer selected from a combinatorial library (5 × 10 14 sequences) binds to TGF-β1 protein with an affinity of 90 nM. In this report, sequence, predicted secondary structure, and binding affinity of the selected thioaptamer (T18_1_3) are presented. KeywordsTransforming growth factor-β1; selection; aptamer; phosphorothioate; thioaptamer; chemiluminescence; entropy Transforming growth factor-β1 (TGF-β1) is a 25 kDa homodimer composed of two 12.5 kDa subunits joined by a disulfide bond. The protein is known as a multifunctional cytokine acting both through autocrine and paracrine mechanisms. The protein suppresses the immune system and is particularly associated with immune disregulation by inhibiting the proliferation of normal T lymphocytes via down-regulation of interleukin-2-mediated proliferative signals. 1 TGF-β1 also mediates tumor-promoting effects, either through differential effects on tumor and stromal cells or through alteration in the TGF-β1 responsiveness of the tumor cells themselves. 2 Inhibition of the TGF-β signaling pathway has been proposed for cancer therapy. 3 Therefore, agents that target and antagonize TGF-β1 may serve as therapeutic or research tools by modulating the function of this protein.Combinatorial selection of oligonucleotide aptamers has been employed to develop potential therapeutic agents since its introduction. 4,5 The principle of this technique is isolation and enrichment of specific nucleic acid sequences (aptamers) that bind to target molecules from a large random combinatorial library. This approach seems especially appropriate as inhibitor Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript development because the protein is known to bind to heparin, a polyanionic polymer like DNA 6 The selection in this study was designed to modify every 5′ of adenosine and cytosine of single-stranded DNA (ssDNA) aptamers to phosphorothioate, since phosphorothioatesubstituted aptamers typically display an enhanced affinity for targeted molecules and increased stability in the biological milieu. 7,8 Several DNA 9,10 and RNA 11,12 ...

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To describe the details of the foraminoplastic superior vertebral notch approach (FSVNA) with reamers in percutaneous endoscopic lumbar discectomy (PELD) and to demonstrate the clinical outcomes in limited indications of PELD. Retrospective data were collected from 64 patients who underwent PELD with FSVNA from August 2012 to April 2014. Inclusion criteria were high grade migrated disc, high canal compromised disc, and disc protrusion combined with foraminal stenosis. The clinical outcomes were assessed using by the visual analogue scale (VAS), Oswestry Disability Index (ODI) and modified MacNab criteria. Complications related to the surgery were reviewed. The procedure used a unique approach, using the superior vertebral notch as the target and performing foraminoplasty with only reamers under C-arm control. The mean age of the 55 female and 32 male patients was 52.73 years. The mean F/U period was 12.2±4.2 months. Preoperative VAS (8.24±1.25) and ODI (67.8±15.4) score improved significantly at the last follow-up (VAS, 1.93±1.78; ODI, 17.14±15.7). Based on the modified MacNab criteria, excellent or good results were obtained in 95.3% of the patients. Postoperative transient dysthesia (n=2) and reoperation (n=1) due to recurred disc were reported. PELD with FSVNA could be a good method for treating lumbar disc herniation. This procedure may offer safe and efficacious results, especially in the relatively limited indications for PELD.