Regeneration in the central nervous system (CNS) of adult mammalian after traumatic injury is limited, which often causes permanent functional motor and sensory loss. After spinal cord injury (SCI), the lack of regeneration is mainly attributed to the presence of a hostile microenvironment, glial scarring, and cavitation. Besides, inflammation has also been proved to play a crucial role in secondary degeneration following SCI. The more prominent treatment strategies in experimental models focus mainly on drugs and cell therapies, however, only a few strategies applied in clinical studies and therapies still have only limited effects on the repair of SCI. Recently, the interests in immunotherapy strategies for CNS are increasing in number and breadth. Immunotherapy strategies have made good progresses in treating many CNS degenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), stroke, and multiple sclerosis (MS). However, the strategies begin to be considered to the treatment of SCI and other neurological disorders in recent years. Besides anti-inflamatory therapy, immunization with protein vaccines and DNA vaccines has emerged as a novel therapy strategy because of the simplicity of preparation and application. An inflammatory response followed by spinal cord injury, and is controled by specific signaling molecules, such as some cytokines playing a crucial role. As a result, appropriate immunoregulation, the expression of pro-inflammatory cytokines and anti-inflammatory cytokines may be an effective therapy strategy for earlier injury of spinal cord. In addition, myelinassociated inhibitors (MAIs) in the injured spinal cord, such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte- myelin glycoprotein (OMgp) are known to prevent axonal regeneration through their co-receptors, and to trigger demyelinating autoimmunity through T cell-mediated harmful autoimmune response. The antagonism of the MAIs through vaccinating with protein or DNA vaccines targeting Nogo, MAG, OMgp, and their co-receptors, may be an effective strategy for the treatment of SCI. However, immunotherapy such as anti-inflammtory therapy or vaccine targeting MAIs or their receptors, accompanied with the potential in risking autoimmune diseases. As a result, in order to optimize the anti-inflammtory therapy and design of protein or DNA vaccines for their use in the future clinical application, we need to further understand the possible mechanisms of neuroprotective immunity. This review presents recent advances in the development of immunotherapy strategies for the treatment of axonal degeneration and demyelination, and improvement of motor function after SCI.

To select tag single nucleotide polymorphisms (SNPs) within and around human p75 neurotrophin receptor (p75NTR) gene in Chinese Han population, the sequence involving p75NTR gene as well as the upstream and downstream of the gene was identified according to the data from National Center for Biotechnology Information (NCBI) GenBank database, and the SNP genotype data involving 63 SNPs in the regions were obtained from Chinese Han Beijing (CHB) population of HapMap database. Then, Haploview (version 4.2) was used to calculate linkage disequilibrium (LD) statistics for the selected 32 common SNPs with a minor allele frequence (MAF) more than 0.05. Haplotype blocks were constructed throughout the p75NTR gene according to the upper and the lower 95% confidence bound of D' value, and the tag SNPs were selected based on the r2 and LOD values between SNPs as well as the results of bioinformatics analysis. The results indicated that five haplotype blocks were constructed within and around p75NTR gene and 12 tag SNPs including rs2537710, rs603769, rs614455, rs2537706, rs534561, rs2072445, rs2072446, rs7219709, rs734194, rs741071, rs741073 and rs2671641 were selected to represent the other 51 SNPs in p75NTR gene. Therefore, the 12 selected SNPs may act as tag SNPs for the entire p75NTR gene in Chinese Han population, which will provide an effective way to select tag SNPs in a whole gene, and its biological significance is to further guide the clinical association studies between the candidate gene and disease susceptibility.

Abstract Objectives: The purpose of this study is to demonstrate a dependence of spinal cord motoneurons on the communication with their targets, sciatic nerves, and investigate whether the effects of nerve growth factor (NGF) on the spinal cord neuron apoptosis and surviving through the regulation of nuclear factor-kappa B (NF-kappaB) in Schwann cells (SCs) in sciatic nerve injured rats. Methods: Ninety healthy adult Sprague–Dawley rats were divided randomly into normal control group, crushing group, and NGF-intervened group. When sciatic nerve crushed 1, 3, 7, 14, and 21 days, the expression of NF-kappaB in SCs and the apoptosis regulator Bcl-2 and Caspase-3 in spinal cord were examined by immunohistochemistry staining, Western blot analysis, and immunofluorescence double-labeling method, the motor neuron apoptosis were investigated by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and the surviving neurons were tested by toluidine blue (Nissl) staining, respectively. All the data were further analyzed with SPSS10·0 application software. Results: The level of the expression of NF-kappaB in crushing group enhanced at 1 day after crushing, reached peak at 3 days, and reduced at least until 21 days, which was markedly higher than that in the normal control group. The expression of NF-kappaB in NGF-intervened group showed the same changes, reached peak at 7 days, and reduced until 21 days. However, when compared with crushing group, the expression of NF-kappaB in NGF-intervened group was down-regulated significantly until 3 days after injury, and up-regulated obviously with time going on. The same trend was observed in the time course on motor neuron apoptosis in crushing group and NGF-intervened group after sciatic nerves injury, while the reversing change was found in the surviving neurons. Moreover, the kinetics of Bcl-2 expression in spinal cord was consistent with that of NF-kappaB, while reversing with that of Caspase-3. Conclusion: The findings revealed that NGF may play a pivotal role of anti-apoptosis in spinal cord neurons through retrograde transport of NF-kappaB in SCs following sciatic nerve injury in rats.

Nucleic acid vaccine is a brand-new vaccine sprung up in 1990s,and has shown its tremendous potentials in immunology and preventive medicals.Up to date,more than 10 DNA vaccines have been approved by FDA to conduct clinical and non-clinical experiments.However,there are still some unsolved problems,such as manufacturing techniques,quality standards,preparation and effects.Among the problems,safety is of major importance as it has a direct bearing on the application of DNA vaccine.Therefore,to address the security concern is the hot-spot and focus of current research on DNA vaccine.For the time being,security risks mainly include gene integration,immunologic diseases,difference of species and individuals,risks emerging in manufacturing process.To this end,we are supposed to optimize the designation and manufacturing of it,mainly from aspects such as expression vector,immunoadjuvant,immunization route,and immunization program.This paper aims to give a review on safety of DNA vaccine as well as optimum strategies,and thus be of significance to fundamental and clinical researches.