Guanosine reduces apoptosis and inflammation associated with restoration of function in rats with acute spinal cord injury.
Spinal cord injury results in progressive waves of secondary injuries, cascades of noxious pathological mechanisms that substantially exacerbate the primary injury and the resultant permanent functional deficits. Secondary injuries are associated with inflammation, excessive cytokine release, and cell apoptosis. The purine nucleoside guanosine has significant trophic effects and is neuroprotective, antiapoptotic in vitro, and stimulates nerve regeneration. Therefore, we determined whether systemic administration of guanosine could protect rats from some of the secondary effects of spinal cord injury, thereby reducing neurological deficits. Systemic administration of guanosine (8 mg/kg per day, i.p.) for 14 consecutive days, starting 4 h after moderate spinal cord injury in rats, significantly improved not only motor and sensory functions, but also recovery of bladder function. These improvements were associated with reduction in the inflammatory response to injury, reduction of apoptotic cell death, increased sparing of axons, and preservation of myelin. Our data indicate that the therapeutic action of guanosine probably results from reducing inflammation resulting in the protection of axons, oligodendrocytes, and neurons and from inhibiting apoptotic cell death. These data raise the intriguing possibility that guanosine may also be able to reduce secondary pathological events and thus improve functional outcome after traumatic spinal cord injury in humans.
Jiang
Shucui
S
Department of Surgery (Neurosurgery), McMaster University, Health Sciences Centre, 4N71B, 1200 Main Street West, Hamilton, L8N 3Z5, ON, Canada, jiangs@mcmaster.ca.
Bendjelloul
Farid
F
Ballerini
Patrizia
P
D'Alimonte
Iolanda
I
Nargi
Elenora
E
Jiang
Cai
C
Huang
Xinjie
X
Rathbone
Michel P
MP