Ciliary Neurotrophic Factor Protects Striatal Neurons against Excitotoxicity by Enhancing Glial Glutamate Uptake

Ciliary neurotrophic factor (CNTF) is a potent neuroprotective cytokine in different animal models of glutamate-induced excitotoxicity, although its action mechanisms are still poorly characterized. We tested the hypothesis that an increased function of glial glutamate transporters (GTs) could underlie CNTF-mediated neuroprotection. We show that neuronal loss induced by in vivo striatal injection of the excitotoxin quinolinic acid (QA) was significantly reduced (by ∼75%) in CNTF-treated animals. In striatal slices, acute QA application dramatically inhibited corticostriatal field potentials (FPs), whose recovery was significantly higher in CNTF rats compared to controls (∼40% vs. ∼7%), confirming an enhanced resistance to excitotoxicity. The GT inhibitor dl-threo-β-benzyloxyaspartate greatly reduced FP recovery in CNTF rats, supporting the role of GT in CNTF-mediated neuroprotection. Whole-cell patch-clamp recordings from striatal medium spiny neurons showed no alteration of basic properties of striatal glutamatergic transmission in CNTF animals, but the increased effect of a low-affinity competitive glutamate receptor antagonist (γ-d-glutamylglycine) also suggested an enhanced GT function. These data strongly support our hypothesis that CNTF is neuroprotective via an increased function of glial GTs, and further confirms the therapeutic potential of CNTF for the clinical treatment of progressive neurodegenerative diseases involving glutamate overflow

Systematic review of Ethiopian medicinal plants used for their anti-inflammatory and wound healing activities

Ethnopharmacological relevance: Plant materials are used worldwide as complementary and alternative therapeutics for the treatment of various illnesses. In Ethiopia, folk medicines are utilized across a wide range of cultures and settings. Ethiopia has numerous plant species of which around 12% are endemic, making it a rich source of medicinal plants that are potentially important for human wellbeing. Aim of the study: The aim of this study was to assess Ethiopian medicinal plants with anti-inflammatory or wound healing activities, in an attempt to compile the information required for further investigation of their potential role in the management of lymphoedema. Methods: A systematic review protocol was developed according to the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) statement. The protocol for this review was registered on PROSPERO with registration number CRD42019127471. This review considers all controlled in vivo and in vitro anti-inflammatory and wound healing studies evaluating the efficacy and safety of Ethiopian medicinal plants. The search strategy included all articles containing descriptors such as Ethiopia, medicinal plants, herbal products, care, management, lymphoedema, lymphedema, swelling, podoconiosis, elephantiasis, wound, wound healing, inflammation, and anti-inflammatory that were published up to June 28, 2019. Outcomes were measured as the percentage of inflammatory and pro-inflammatory cell inhibition, as the percentage of carrageenan-induced oedema (anti-inflammation) inhibition, and the percentage of cell migration and proliferation (wound healing). For quality assessment of individual animal studies, the Risk of Bias tool for animal intervention studies (SYRCLE’s RoB tool) criteria was used. For quality assessment of individual in vitro studies, the OECD guidelines and the WHO Good Laboratory Practice (GLP) handbook were used. Results: A total of 46 articles on anti-inflammatory and 17 articles on wound healing properties were reviewed. For the in vivo studies, Swiss albino mice and Wistar rats were used, and the concentration of plant extracts or fractions administered to the lab animals varied considerably. Acetone extract of Vernonia amygdalina showed the fastest anti-inflammatory activity at lower concentrations in carrageenan-induced paw oedema. Conclusion: Lawsonia inermis, Azadirachta indica, Achyranthes aspera, and Cuminum cyminum are the most studied plant species in terms of anti-inflammatory activity, while Lawsonia inermis and Azadirachta indica are the most studied for wound healing. The most common in vivo techniques used for the anti-inflammatory and the wound healing assays were carrageenan-induced paw oedema, and excision and incision wound models, respectively

The role of the carotid sinus in the reduction of arterial wall stresses due to head movements--potential implications for cervical artery dissection

Spontaneous dissection of the cervical internal carotid artery (sICAD) is a major cause of stroke in young adults. A tear in the inner part of the vessel wall triggers sICAD as it allows the blood to enter the wall and develop a transmural hematoma. The etiology of the tear is unknown but many patients with sICAD report an initiating trivial trauma. We thus hypothesised that the site of the tear might correspond with the location of maximal stress in the carotid wall. Carotid artery geometries segmented from magnetic resonance images of a healthy subject at different static head positions were used to define a path of motion and deformation of the right cervical internal carotid artery (ICA). Maximum head rotation to the left and rotation to the left combined with hyperextension of the neck were investigated using a structural finite element model. A role of the carotid sinus as a geometrically compliant feature accommodating extension of the artery is shown. At the extreme range of the movements, the geometrical compliance of the carotid sinus is limited and significant stress concentrations appear just distal to the sinus with peak stresses at the internal wall on the posterior side of the vessel following maximum head rotation and on the anteromedial portion of the vessel wall following rotation and hyperextension. Clinically, the location of sICAD initiation is 10-30 mm distal to the origin of the cervical ICA, which corresponds with the peak stress locations observed in the model, thus supporting trivial trauma from natural head movements as a possible initiating factor in sICAD