Introduction 1 3 4 7 8 11 12 14 15 16 19 3 20 22 23 24 25 28 25 28 25 27 25 29 30 31 Materials and methods All experiments were performed in compliance with the requirements of the Animals for Research Act of Ontario, Canada and the Guidelines of the Canadian Council on Animal Care, and had been approved by the Animal Research Ethics Board of McMaster University. Spinal cord injury 2 31 33 31 34 35 Behavioural assessment and drug administration 36 37 31 BrdU administration Tissue processing and immunohistochemistry 38 Elite 39 Quantification n n 39 Evaluation of exogenous guanosine distribution g g 40 Tissue concentrations of guanosine and guanine 2 4 3D Statistical analysis p Results and discussion 1 1 1 r p 1 1 1 Fig. 1 a Materials and methods b p c d d c d c DC e Materials and methods p p f g h h g IS i j  2 p 2 Fig. 2 a b a b b a c d e in green in red d e f h f g f g i j h j  41 42 43 14 44 43 45 48 2 2 2 2 2 2 2 2 p 2 3 49 3 p Fig. 3 a b in red a b c d c d d e c e p  50 52 15 53 55 4 Fig. 4 a b  5 5 5 Fig. 5 a b  3 12 13 56 Whether the effects on remyelination are due to guanosine, guanine or both is not clear. However, since a putative receptor for guanosine has been identified in the CNS, and since PNP (purine nucleoside phosphorylase) in CNS permits the interconversion of guanine and guanosine enabling guanine to act as a reservoir for guanosine, it is possible that guanosine may be responsible for causing the proliferation of the endogenous progenitor cells and the subsequent remyelination process, although this is by no means certain. But, since guanine itself is difficult to administer because of its poor solubility, administration of guanosine is the most effective delivery mechanism. 25 3 16 57 58 61 18 19 62 63 64 The present findings are the first to show that systemic treatment with guanosine after chronic SCI induces an improvement in function that is accompanied by the formation of mature oligodendrocytes. This effect of guanosine/guanine may be attributable to direct or indirect stimulation of endogenous oligodendrocyte lineage progenitors in the spinal cord and remyelination of axons at the injury site. 65 70