Involvement of metabotropic glutamate receptors in excitatory amino acid and GABA release following spinal cord injury in rat

Spinal cord injury (SCI) leads to an increase in extracellular excitatory amino acid (EAA) concentrations resulting in glutamate receptor-mediated excitotoxic events. The glutamate receptors include ionotropic (iGluRs) and metabotropic (mGluR) receptors. Of the three groups of mGluRs, group-I activation can initiate intracellular pathways that lead to further transmitter release. Groups II and III mGluRs function mainly as autoreceptors to regulate neurotransmitter release. In an effort to examine the role of mGluRs in the increase in EAAs following SCI, we administered AIDA, a potent group-I mGluR antagonist immediately after injury. To determine subtype specific roles of the group-I mGluRs, we evaluated EAA release following LY 367385 (mGluR1 antagonist) and MPEP (mGluR5 antagonist) administration. To evaluate group-II and -III mGluRs we administered APDC (group-II agonist) and L-AP4 (group-III agonist) immediately following injury; additionally, we initiated treatment with CPPG (group-II/-III antagonist) and LY 341495 (group-II antagonist) 5 min prior to injury. Subjects were adult male Sprague-Dawley rats (225-250 g), impact injured at T10 with an NYU impactor (12.5 mm drop). Agents were injected into the epicenter of injury, amino acids where collected by microdialysis fibers inserted 0.5 mm caudal from the edge of the impact region and quantified by HPLC. Treatment with AIDA significantly decreased extracellular EAA and GABA concentrations. MPEP reduced EAA concentrations without affecting GABA. Combining LY 367385 and MPEP resulted in a decrease in EAA and GABA concentrations greater than either agent alone. L-AP4 decreased EAA levels, while treatment with LY 341495 increased EAA levels. These results suggest that mGluRs play an important role in EAA toxicity following SCI.     

Gβ1 controls collective cell migration by regulating the protrusive activity of leader cells in the posterior lateral line primordium

Collective cell migration is critical for normal development, tissue repair and cancer metastasis. Migration of the posterior lateral line primordium (pLLP) generates the zebrafish sensory organs (neuromasts, NMs). This migration is promoted by the leader cells at the leading edge of the pLLP, which express the G protein-coupled chemokine receptor Cxcr4b and respond to the chemokine Cxcl12a. However, the mechanism by which Cxc112a/Cxcr4b signaling regulates pLLP migration remains unclear. Here we report that signal transduction by the heterotrimeric G protein subunit Gβ1 is essential for proper pLLP migration. Although both Gβ1 and Gβ4 are expressed in the pLLP and NMs, depletion of Gβ1 but not Gβ4 resulted in an arrest of pLLP migration. In embryos deficient for Gβ1, the pLLP cells migrated in an uncoordinated fashion and were unable to extend protrusions at the leading front, phenocopying those in embryos deficient for Cxcl12a or Cxcr4b. A transplantation assay showed that, like Cxcr4b, Gβ1 is required only in the leader cells of the pLLP. Analysis of F-actin dynamics in the pLLP revealed that whereas wild-type leader cells display extensive actin polymerization in the direction of pLLP migration, counterparts defective for Gβ1, Cxcr4b or Cxcl12a do not. Finally, synergy experiments revealed that Gβ1 and Cxcr4b interact genetically in regulating pLLP migration. Collectively, our data indicate that Gβ1 controls migration of the pLLP, likely by acting downstream of the Cxcl12a/Cxcr4b signaling. This study also provides compelling evidence for functional specificity among Gβ isoforms in vivo.     

Effects of cerebrolysin on motor-neuron-like NSC-34 cells

Although the peripheral nervous system is capable of regeneration, this capability is limited. As a potential means of augmenting nerve regeneration, the effects of cerebrolysin (CL) – a proteolytic peptide fraction – were tested in vitro on the motor-neuron-like NSC-34 cell line and organotypic spinal cord cultures. Therefore, NSC-34 cells were subjected to mechanical stress by changing media and metabolic stress by oxygen glucose deprivation. Afterwards, cell survival/proliferation using MTT and BrdU-labeling (FACS) and neurite sprouting using ImageJ analysis were evaluated. Calpain-1, Src and α-spectrin protein expression were analyzed by Western blot. In organotypic cultures, the effect of CL on motor neuron survival and neurite sprouting was tested by immunohistochemistry.     

MRI metrics at the epicenter of spinal cord injury are correlated with the stepping process in rhesus monkeys

Clinical evaluations of long-term outcomes in the early-stage spinal cord injury (SCI) focus on macroscopic motor performance and are limited in their prognostic precision. This study was designed to investigate the sensitivity of the magnetic resonance imaging (MRI) indexes to the data-driven gait process after SCI. Ten adult female rhesus monkeys were subjected to thoracic SCI. Kinematics-based gait examinations were performed at 1 (early stage) and 12 (chronic stage) months post-SCI. The proportion of stepping (PS) and gait stability (GS) were calculated as the outcome measures. MRI metrics, which were derived from structural imaging (spinal cord cross-sectional area, SCA) and diffusion tensor imaging (fractional anisotropy, FA; axial diffusivity, λ_//), were acquired in the early stage and compared with functional outcomes by using correlation analysis and stepwise multivariable linear regression. Residual tissue SCA at the injury epicenter and residual tissue FA/remote normal-like tissue FA were correlated with the early-stage PS and GS. The extent of lesion site λ_///residual tissue λ_// in the early stage after SCI was correlated with the chronic-stage GS. The ratios of lesion site λ_// to residual tissue λ_// and early-stage GS were predictive of the improvement in the PS at follow-up. Similarly, the ratios of lesion site λ_// to residual tissue λ_// and early-stage PS best predicted chronic GS recovery. Our findings demonstrate the predictive power of MRI combined with the early data-driven gait indexes for long-term outcomes. Such an approach may help clinicians to predict functional recovery accurately.     

Prosthetic valve endocarditis: management strategies and prognosis

Background Prosthetic valve endocarditis (PVE) is a rare and serious complication after heart valve replacement; its optimal management strategy, though, still needs to be defined. Objective To study the clinical, microbiological and echocardiographic characteristics of PVE and to analyse the influence of the adopted therapeutic strategy (medical or surgical) on short- and midterm outcome in a tertiary care centre in a developing country (Tunisia). Methods All cases of PVE treated in our institution between 1997 and 2006 were retrospectively analysed according to the modified DUKE criteria. Results A total of 48 PVE episodes were diagnosed (30 men and 18 women), mean age was 37.93 years. Twenty-eight patients (58.33%) were exclusively medically treated, whereas 20 (41.66%) were treated by a combined surgical and medical strategy. Indications for surgery were haemodynamic deterioration in eight patients (40%), annular abscess in six (30%) and persisting sepsis in six (30%). In comparison with those from the medical group, operated patients had a longer delay to diagnosis (p=0.025), were more frequently in heart failure (p=0.04) and experienced more early complications (p=0.011); they also more frequently had prosthetic dehiscence (p=0.015), annular abscesses (p=0.039) and vegetations >10 mm (p=0.008). Conversely, no differences were found between the groups in terms of age, sex, or nature of involved organisms. In-hospital mortality for the medical group was 14.28% and for the surgical group 35% (p=0.09). Conclusion PVE is a very serious condition carrying high mortality rates regardless of the adopted strategy. Our study demonstrates that, in selected patients, medical treatment could be a successful and acceptable approach. (Neth Heart J 2009;17: 56-60.)     

Glutamate regulates neurite outgrowth of cultured descending brain neurons from larval lamprey

In larval lamprey, descending brain neurons, which regenerate their axons following spinal cord injury, were isolated and examined in cell culture to identify some of the factors that regulate neurite outgrowth. Focal application of 5 mM or 25 mM L-glutamate to single growth cones inhibited outgrowth of the treated neurite, but other neurites from the same neuron were not inhibited, an effect that has not been well studied for neurons in other systems. Glutamate-induced inhibition of neurite outgrowth was abolished by 10 mM kynurenic acid. Application of high potassium media to growth cones inhibited neurite outgrowth, an effect that was blocked by 2 mM cobalt or 100 microM cadmium, suggesting that calcium influx via voltage-gated channels contributes to glutamate-induced regulation of neurite outgrowth. Application of glutamate to growth cones in the presence of 2 microM omega-conotoxin MVIIC (CTX) still inhibited neurite outgrowth, while CTX blocked high potassium-induced inhibition of neurite outgrowth. Thus, CTX blocked virtually all of the calcium influx resulting from depolarization. To our knowledge, this is the first direct demonstration that calcium influx via ligand-gated ion channels can contribute to regulation of neurite outgrowth. Finally, focal application of glutamate to the cell bodies of descending brain neurons inhibited outgrowth of multiple neurites from the same neuron, and this is the first demonstration that multiple neurites can be regulated in this fashion. Signaling mechanisms involving intracellular calcium, similar to those shown here, may be important for regulating axonal regeneration following spinal cord injury in the lamprey.     

体外循环心脏手术围术期脑损伤监测进展

脑损伤是体外循环心脏手术的严重并发症之一,目前患病人数在全球范围内呈逐年增高的趋势,并且临床上应用的脑保护措施效果并不确切,因此有效的神经系统监测关系到外科手术的成败和病人的预后。本文从术中脑组织氧供需平衡、栓子的监测、生化标志物和术后神经功能监测四个方面综述目前脑损伤监测的新进展。     

Body image and quality of life in post massive weight loss body contouring patients

Objective: Because post‐bariatric surgery patients undergo massive weight loss, the resulting skin excess can lead to both functional problems and profound dissatisfaction with appearance. Correcting skin excess could improve all these corollaries, including body image. Presently, few data are available documenting body image and weight‐related quality of life in this population. Research Methods and Procedures: Eighteen patients who underwent both bariatric surgery and body contouring completed our study. Both established surveys and new surveys designed specifically for the study were used to assess body perception and ideals, quality of life, and mood. Patients were surveyed at the following time‐points: pre‐body contouring (after massive weight loss) and both 3 and 6 month post‐body contouring. Statistical testing was performed using Student's t test and ANOVA. Results: The mean age of the patients was 46 ± 10 years (standard deviation). Quality of life improved after obesity surgery and was significantly enhanced after body contouring. Three months after body contouring, subjects ascribed thinner silhouettes to both current appearance and ideal body image. Body image also improved with body contouring surgery. Mood remained stable over 6 months. Discussion: Body contouring after surgical weight loss improved both quality‐of‐life measurements and body image. Initial body dissatisfaction did not correlate with mood. Body contouring improved body image but produced dissatisfaction with other parts of the body, suggesting that as patients become closer to their ideal, these ideals may shift. We further developed several new assessment methods that may prove useful in understanding these post‐surgical weight loss patients.