Neuroprotection from inflammation: Experimental allergic encephalomyelitis facilitates traumatic spinal cord injury recovery

Passive immunization with T cells activated against central nervous system (CNS) - associated myelin antigens has been found to provide neuroprotection following CNS trauma, leading to the concept of protective autoimmunity. However, limited research exists about whether actively induced CNS autoimmunity may offer any similar benefit. In this study, the kinetics and the effect of endogenously anti-myelin activated T cells following spinal cord injury (SCI), were investigated. Experimental allergic encephalomyelitis (EAE) was actively induced in Lewis rats following immunization with myelin basic protein (MBP). In vivo 5-Bromo-2-deoxyuridine (BrdU) incorporation from activated T cells was used as a marker of T cell- proliferation. BrdU was injected on 5th, 6th and 7th day post-induction (DPI) at all EAE-animals. On DPI 8, spinal cord compressive injury was induced by a transient extradural application of an aneurysm clip at the T8 spinal level. SCI resulted in spastic paralysis of hindlimbs, in all but sham-injured animals. Recovery from SCI was significantly better in EAE-animals. Activated mononuclear cells were selectively accumulated at the site of the injury. Axonal loss was less in the EAE group following SCI. Our findings indicate that actively induced autoimmunity against CNS myelin antigens may protect spinal cord pathways from mechanical injury

Modified Beilschowsky silver impregnation combined with Hematoxylin or Cresyl Violet counterstaining as a potential tool for the simultaneous study of inflammation and axonal injury in the central nervous system

Background: Hematoxylin-Eosin (H&E), Cresyl Violet and Bielschowsky Silver Impregnation (BSI) are among the basic histological methods for the evaluation of inflammation and axonal injury in the Central Nervous System (CNS). The usual strategy so far is staining serial sections of CNS separately for H&E and BSI, whilst the simultaneous application of both methods on a single brain section could give more accurate information for both inflammatory and degenerative components. However, the classical protocols for BSI have unstable reproducibility, high staining background and, evidently, hematoxylin is not easily applied. Materials-Methods: Brain sections from Experimental Allergic Encephalomyelitis (EAE) and Traumatic Brain Injury (TBI) animal models were used. Different pH and incubation periods in the process of BSI staining were investigated to establish a reproducible protocol with minimal background. Results: The pH of the BSI working solutions strongly affect the final results of the method and the application of specific pHs almost eliminate background up to a point where H&E or cresyl violet counterstaining can easily be applied. Conclusion: The proposed combination is cost effective, has minimal background and increased reproducibility. It is proposed as a basic screening tool in the study of CNS disorders, namely those where inflammatory process and axonal pathology coexist

Phase III, randomised, double-blind, placebo-controlled trial of Neuroaspis plp10 as an adjuvant treatment for relapsing multiple sclerosis: the MINERAL Study

Objectives To assess the effectiveness of Neuroaspis plp10 nutritional supplement when added to interferon (IFN)-β treatment in patients with relapsing-remitting multiple sclerosis (RRMS).Design A 30-month phase III multicentre, randomised, double-blind, placebo-controlled trial. Randomisation stratified by centre using a computer-generated procedure with Neuroaspis plp10 versus placebo in 1:1 ratio. The first 6 months were used as both the pre-entry and normalisation period.Setting 3 teaching hospitals in Greece and 1 Neurology Institute in Cyprus.Participants 61 patients with RRMS on IFN-β were randomly assigned to receive Neuroaspis plp10 (n=32) or placebo (n=29), 20 mL, orally, once daily, for 30 months.Intervention Neuroaspis plp10, a cocktail mixture, containing specific PUFA (12 150 mg) and γ-tocopherol (760 mg) versus virgin olive oil (placebo).Main outcome measure The primary end point was the annual relapse rate (ARR) whereas the secondary ones were the rate of sustained progression of disability, as measured by the Expanded Disability Status Scale (EDSS) and the brain T2 and gadolinium-enhancing lesions, at 2 years.Results For the intention-to-treat analyses Neuroaspis plp10 significantly reduced the ARR by 80%, (RRR, 0.20; 95% CI: 0.09 to 0.45; p=0.0001) and the risk of sustained progression of disability by 73% (HR, 0.27; 95% CI: 0.09 to 0.83; p=0.022) versus placebo, at 2 years. The number of T1 gadolinium-enhancing lesions and the number of new/enlarged T2-hyperintense lesions were significantly reduced (p=0.01 and p<0.0001, respectively). Both T1-enhancing and new/enlarging T2-hyperintense lesions were significantly reduced (p=0.05 and p<0.0001, respectively). No significant adverse events were reported.Conclusions Neuroaspis plp10 added to IFN-β was significantly more effective than IFN-β alone in patients with RRMS.Trial registration number ISRCTN06166891