GAS6 Enhances Repair Following Cuprizone-Induced Demyelination

Growth arrest-specific protein 6 (gas6) activities are mediated through the Tyro3, Axl, and Mer family of receptor tyrosine kinases. Gas6 is expressed and secreted by a wide variety of cell types, including cells of the central nervous system (CNS). In this study, we tested the hypothesis that administration of recombinant human Gas6 (rhGas6) protein into the CNS improves recovery following cuprizone withdrawal. After a 4-week cuprizone diet, cuprizone was removed and PBS or rhGas6 (400 ng/ml, 4 µg/ml and 40 µg/ml) was delivered by osmotic mini-pump into the corpus callosum of C57Bl6 mice for 14 days. Nine of 11 (82%) PBS-treated mice had abundant lipid-associated debris in the corpus callosum by Oil-Red-O staining while only 4 of 19 (21%) mice treated with rhGas6 had low Oil-Red-O positive droplets. In rhGas6-treated mice, SMI32-positive axonal spheroids and APP-positive deposits were reduced in number relative to PBS-treated mice. Compared to PBS, rhGas6 enhanced remyelination as revealed by MBP immunostaining and electron microscopy. The rhGas6-treated mice had more oligodendrocytes expressing Olig1 in the cytoplasm, indicative of oligodendrocyte progenitor cell maturation. Relative to PBS-treated mice, rhGas6-treated mice had fewer activated microglia in the corpus callosum by Iba1 immunostaining. The data show that rhGas6 treatment resulted in more efficient repair following cuprizone-induced injury

Postsynaptic nigrostriatal dopamine receptors and their role in movement regulation

The article presents the hypothesis that nigrostriatal dopamine may regulate movement by modulation of tone and contraction in skeletal muscles through a concentration-dependent influence on the postsynaptic D1 and D2 receptors on the follow manner: nigrostriatal axons innervate both receptor types within the striatal locus somatotopically responsible for motor control in agonist/antagonist muscle pair around a given joint. D1 receptors interact with lower and D2 receptors with higher dopamine concentrations. Synaptic dopamine concentration increases immediately before movement starts. We hypothesize that increasing dopamine concentrations stimulate first the D1 receptors and reduce muscle tone in the antagonist muscle and than stimulate D2 receptors and induce contraction in the agonist muscle. The preceded muscle tone reduction in the antagonist muscle eases the efficient contraction of the agonist. Our hypothesis is applicable for an explanation of physiological movement regulation, different forms of movement pathology and therapeutic drug effects. Further, this hypothesis provides a theoretical basis for experimental investigation of dopaminergic motor control and development of new strategies for treatment of movement disorders

Does Hardware Removal Improve Function Following Ankle Open Reduction and Internal Fixation?

Category: Ankle, Trauma Introduction/Purpose: Orthopaedic hardware removal (HWR) is one of the most common orthopaedic procedures performed, with rates reported between 5% and 16%. Despite the high rates of HWR, there is still no consensus or guideline for removal after osseous healing without infection. Outcome studies for HWR are scarce, particularly in the lower extremity. The purpose of this study is to evaluate the effect of removal of symptomatic ankle hardware using the Short Musculoskeletal Function Assessment (SMFA) dysfunction index as the primary outcome. We hypothesize that HWR after ankle fracture will result in improved functional outcomes. Methods: Utilizing a prospectively collected ankle fracture registry, all patients that underwent HWR between 2013 and 2016 were retrospectively reviewed. Inclusion criteria were skeletal maturity, closed intra-articular ankle fracture, symptomatic ankle hardware and completion of the SMFA questionnaire prior to and 5-months after hardware removal. Exclusion criteria were development of a nonunion, infection or complex regional pain syndrome from initial surgery. The primary outcome was change in SMFA score from baseline. Paired t-test was used to compare baseline and follow-up SMFA scores. A multiple linear regression model evaluated the effects of age, sex, body mass index (BMI), smoking status, number of comorbidities, and Lauge-Hansen fracture classification on outcomes. Results: The study included 43 patients (31 females, 12 males), mean age 49.9 (range, 19 to 83). Mean time from initial surgery to HWR was 37±46 months (range, 2.2 to 209). Follow-up SMFA questionnaires were completed 5.7±0.5 months (range, 5.1 to 7.4) after HWR. The fractures were classified as 23 (53%) supination-external rotation, 6 (14%) pronation-external rotation, 2 (4.7%) pronation-abduction and 1 (2.3%) supination-adduction. Eleven fractures (26%) were classified as pilons. The SMFA dysfunction index improved significantly from baseline to follow-up (3.71±7.4, p=0.002). Significant improvement was seen in the secondary outcomes of SMFA bother index (4.40±8.9, p=0.003) and SMFA daily activities domain (4.12±9.1, p=0.006). Regression analysis revealed a significant improvement in the bother index correlating with female gender (p=0.01) and decreasing number of comorbidities (p=0.03). Conclusion: Our study demonstrates that patients with ankle fractures have a significant improvement in function following the removal of symptomatic ankle hardware. Patients also showed a significant improvement in the bother index and daily activities domain of the SMFA. Further investigation into the specific indications for HWR and the impact of injury and fracture pattern on outcomes is warranted