Purinergic Signalling (2008) 4:61–71 DOI 10.1007/s11302-007-9093-8 ORIGINAL ARTICLE Remyelination after chronic spinal cord injury is associated with proliferation of endogenous adult progenitor cells after systemic administration of guanosine Shucui Jiang & Patrizia Ballerini & Silvana Buccella & Patricia Giuliani & Cai Jiang & Xinjie Huang & Michel P. Rathbone Received: 3 October 2007 / Accepted: 4 December 2007 / Published online: 8 January 2008 # Springer Science + Business Media B.V. 2007 Abstract Axonal demyelination is a consistent pathological sequel to chronic brain and spinal cord injuries and disorders that slows or disrupts impulse conduction, causing further functional loss. Since oligodendroglial progenitors are present in the demyelinated areas, failure of remyelination may be due to lack of sufficient proliferation and differen- tiation of oligodendroglial progenitors. Guanosine stimu- lates proliferation and differentiation of many types of cells in vitro and exerts neuroprotective effects in the central nervous system (CNS). Five weeks after chronic traumatic spinal cord injury (SCI), when there is no ongoing recovery of function, intraperitoneal administration of guanosine daily for 2 weeks enhanced functional improvement correlated with the increase in myelination in the injured cord. Emphasis was placed on analysis of oligodendrocytes and NG2-positive (NG2+) cells, an endogenous cell S. Jiang (*) Department of Surgery (Neurosurgery, Neurobiology), McMaster University, Health Sciences Centre, 4E15, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada e-mail: jiangs@mcmaster.ca C. Jiang : X. Huang : M. P. Rathbone Department of Medicine (Neurology, Neuropharmacology), McMaster University, Health Sciences Centre, 4E15, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada P. Ballerini : S. Buccella : P. Giuliani Department of Biomedical Sciences, Universita Degli Studi “G. D’Annunzio”, University of Chieti, Nuovo Polo Didattico, Via Dei Vestini, 31, Chieti 66013, Italy population that may be involved in oligodendrocyte replacement. There was an increase in cell proliferation (measured by bromodeoxyuridine staining) that was attrib- utable to an intensification in progenitor cells (NG2+ cells) associated with an increase in mature oligodendrocytes (determined by Rip+ staining). The numbers of astroglia increased at all test times after administration of guanosine whereas microglia only increased in the later stages (14 days). Injected guanosine and its breakdown product guanine accumulated in the spinal cords; there was more guanine than guanosine detected. We conclude that func- tional improvement and remyelination after systemic admin- istration of guanosine is due to the effect of guanosine/ guanine on the proliferation of adult progenitor cells and their maturation into myelin-forming cells. This raises the possibility that administration of guanosine may be useful in the treatment of spinal cord injury or demyelinating diseases such as multiple sclerosis where quiescent oligodendroglial progenitors exist in demyelinated plaques. Keywords Cell proliferation . Functional recovery . Guanine . Guanosine . Immunohistochemistry . Myelination . Oligodendrocyte . Precursors . Spinal cord Abbreviations BBB Basso-Beattie-Bresnahan locomotor rating scale bFGF basic fibroblast growth factor BrdU bromodeoxyuridine CE capillary electrophoresis CNS central nervous system DAB diaminobenzidine FITC fluorescein isothiocyanate GFAP glial fibrillary acidic protein DO09093; No of Pages