64 Purinergic Signalling (2008) 4:61–71 Fig. 1 Systemic treatment with guanosine improves locomotor function and correlates with increased myelination in rats with stable chronic spinal cord injury. a After spinal cord crush, locomotor function was assessed in an open field walking task (OFWT) and scored using a standard scale (“Materials and methods”). No further improvement in locomotor performance occurred after 28 days. b On days 35–48 after injury (days 1 to 14 of treatment in the figure; the first test done immediately prior to the first treatment), animals were randomly divided into two groups. One group received guanosine ▴(), the other group received vehicle (♦). The locomotor function in the control group did not change significantly throughout the 14 days of vehicle administration. In contrast, rats that received guanosine showed a marked improvement in locomotor behaviour, which was significantly ( p < 0.05) better than vehicle-treated control animals from the 5th day of treatment onward. c, d Luxol fast blue staining of cross sections of spinal cords from guanosine- (d) and vehicle- (c) treated animals at the lesion site 48 days after the initial lesion (after 14 days treatment) shows increased Luxol fast blue-stained material in d compared to the vehicle-treated control group in c. DC dorsal column at the lesion. Scale bar = 50 μm. e The total area of each section and of the Luxol fast blue-stained portion were measured following the protocol in “Materials and methods”. The quantitative results show that the cords from guanosine-treated animals had significantly greater myelinated area (*p < 0.05), as estimated from the Luxol fast blue staining, than cords from vehicle-treated control animals, which in turn had significantly less myelinated area (**p < 0.001) than unoperated animals. f Correlation between behavioural and histological outcomes was analysed using regression analysis. The data show that the Luxol fast blue-stained area in the injured cords from animals treated with guanosine correlated with their behavioural recovery in open field walking scores, correlation coefficient of 0.72, indicating that the recovery of function may be related to the increase in myelin. Myelin immunofluorescent staining of cross sections of spinal cords from vehicle- (g) and guanosine- (h) treated animals at the lesion site 14 days after treatment shows that guanosine-treated cords (h) contained more myelin basic protein (MBP)-positive profiles from central nervous system at the injured site compared to the vehicle- treated control group (g). IS injured site. Whereas, in i (vehicle-treated cord) and j (guanosine-treated cord) immunolabelling with specific markers for Schwann cell myelin P0 indicated that Schwann cells from the peripheral nervous system did not contribute to guanosine-induced remyelination. Scale bar = 50 μm for all