Regulation of the JAK/STAT signaling pathway in spinal cord injury: an updated review

The interface between the blood circulation and the neural tissue features unique characteristics that are encompassed by the term 'blood-brain barrier' (BBB). The main functions of this barrier, namely maintenance of brain homeostasis, regulation of influx and efflux transport, and protection from harm, are determined by its specialized multicellular structure. Every constituent cell type makes an indispensable contribution to the BBB's integrity. But if one member of the BBB fails, and as a result the barrier breaks down, there can be dramatic consequences and neuroinflammation and neurodegeneration can occur. In this Review, we highlight recently gained mechanistic insights into the development and maintenance of the BBB. We then discuss how BBB disruption can cause or contribute to neurological disease. Finally, we examine how this knowledge can be used to explore new possibilities for BBB repair.

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As a fulcrum of many vital cellular processes, the JAK/STAT pathway constitutes a rapid membrane-to-nucleus signaling module and induces the expression of various critical mediators of cancer and inflammation. Growing evidence suggests that dysregulation of the JAK/STAT pathway is associated with various cancers and autoimmune diseases. In this review, we discuss the current knowledge about the composition, activation, and regulation of the JAK/STAT pathway. Moreover, we highlight the role of the JAK/STAT pathway and its inhibitors in various diseases.

Background Spinal cord injury (SCI) is a traumatic event that impacts a patient’s physical, psychological, and social well-being and places substantial financial burden on health care systems. To determine the true impact of SCI, this systematic review aims to summarize literature reporting on either the incidence or prevalence of SCI. Methods A systematic search was conducted using PubMed, MEDLINE, MEDLINE in process, EMBASE, Cochrane Controlled Trial Register, and Cochrane Database of Systematic Reviews to identify relevant literature published through June 2013. We sought studies that provided regional, provincial/state, or national data on the incidence of SCI or reported estimates of disease prevalence. The level of evidence of each study was rated using a scale that evaluated study design, methodology, sampling bias, and precision of estimates. Results The initial search yielded 5,874 articles, 48 of which met the inclusion criteria. Forty-four studies estimated the incidence of SCI and nine reported the prevalence, with five discussing both. Of the incidence studies, 14 provided figures at a regional, ten at a state or provincial level and 21 at a national level. The prevalence of SCI was highest in the United States of America (906 per million) and lowest in the Rhone-Alpes region, France (250 per million) and Helsinki, Finland (280 per million). With respect to states and provinces in North America, the crude annual incidence of SCI was highest in Alaska (83 per million) and Mississippi (77 per million) and lowest in Alabama (29.4 per million), despite a large percentage of violence injuries (21.2%). Annual incidences were above 50 per million in the Hualien County in Taiwan (56.1 per million), the central Portugal region (58 per million), and Olmsted County in Minnesota (54.8 per million) and were lower than 20 per million in Taipei, Taiwan (14.6 per million), the Rhone-Alpes region in France (12.7 per million), Aragon, Spain (12.1 per million), Southeast Turkey (16.9 per million), and Stockholm, Sweden (19.5 per million). The highest national incidence was 49.1 per million in New Zealand, and the lowest incidences were in Fiji (10.0 per million) and Spain (8.0 per million). The majority of studies showed a high male-to-female ratio and an age of peak incidence of younger than 30 years old. Traffic accidents were typically the most common cause of SCI, followed by falls in the elderly population. Conclusion This review demonstrates that the incidence, prevalence, and causation of SCI differs between developing and developed countries and suggests that management and preventative strategies need to be tailored to regional trends. The rising aging population in westernized countries also indicates that traumatic SCI secondary to falls may become an increasing public health challenge and that incidence among the elderly may rise with increasing life expectancy.