Traumatic brain injury complicated by sepsis is associated with modification of the amount and the structure of sialic acids

Sialic acids are carboxylated sugars, mostly located in glycoconjugate saccharidic chains, that are responsible for membrane stability and modulation of several intercellular phenomena. Changes of their chemical structure, by addition of O-acetyl groups, and/or of the type of link to the underlying sugar chains, modify their functional properties. Neuronal cell membranes are rich in gangliosides, glicolipids containing several sialic acid residues, that play an important role in brain physiology and pathology, such as inflammatory processes. Recently it has been demonstrated that polysialic acid (PSA), a linear homopolymer attached to the neural cell adhesion molecule (NCAM), has a central role in restoring adult injured tissue by creating conditions permissive for architectural remodeling. In a rat model of traumatic brain injury (Controlled Cortical Impact, CCI), brain recovery is delayed when complicated by sepsis (Caecal Ligation and Puncture, CLP), that induces and maintains a dramatic perilesional microglia activation as feature of a persistent inflammatory response. The aim of this study was to evaluate changes in PSA content (by immunohistochemistry), expression of sialic acid and the different types of sialic acid residues (by lectin histochemistry) when sepsis is superimposed to traumatic brain injury. The evaluations were carried out 7 and 14 days from CCI or CCI+CLP. Our results showed that sepsis associated with CCI causes a decrease in PSA expression and an increase in sialic acid residues, in particular those acetylated at carbon position 7, 8 and 9, in perilesional cortex compared with CCI alone (P< 0.05). Our findings suggest that the sepsis-dependent PSA downregulation may be implied in the delay of tissue repair processes. Moreover, the changes in sialic acid amount and the alteration of their structure could be involved in maintaining microglia activation.