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Browsing by Subject "pleiotrofiini"

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  • Lipponen, Aino (2020)
    Spinal cord injury (SCI) in human patients is the most expensive clinical condition worldwide, restricting individuals’ ability to manage with daily-life activities independently. With very limited available treatment possibilities, the understanding and validating of regenerative mechanisms and treatment options in animal models is crucial for their translation to clinical practice. The majority of SCIs in human patients are contusive in the cervical level of the spinal cord. However, thoracic injury rodent model is more commonly studied, with only recent studies working with cervical contusion injury model. Chondroitin sulphate proteoglycans (CSPGs), and especially their CS chains, are thought to be the major inhibitory structures for neurite regeneration after SCI. However, current research has led to a new idea that the inhibitory effect of CS chains can be reversed to regeneration enhancing by heparin-binding growth-associated molecule (HB-GAM). This endogenously secreted molecule is highly up-regulated in the central nervous system (CNS) during postnatal development, but in the adult CNS the expression is down-regulated. This suggests that postnatal-level concentrations might be needed for inducing neurite regeneration in adult CNS. In this study, HB-GAM treatment was tested on both cervical hemicontusion and hemisection injury models. Here we show that repeated intrathecal injections of HB-GAM were sufficient to increase grey matter myelin optical density in mouse hemicontusion injury model, and partly induce functional recovery in hemisection model. Obtained anatomical evidence suggests that enhanced myelination is potentially involved in the repair mechanism of HB-GAM. The connection between HB-GAM treatment and functional recovery, and also other mechanisms of HB-GAM-induced regeneration need further exploration. In broader perspective, the results are promising for translation of a novel treatment approach to clinical use.