As a consequence of secondary pathophysiological mechanisms elicited after spinal cord injury (SCI), oligodendrocytes die by waves of apoptosis. This ultimately results in demyelination of intact axons leading to a loss of their conducting properties. Preservation of as few as 5% to 10% of myelinated axons in individual tracts can confer locomotor recovery. Thus, strategies aimed at rescuing mature oligodendrocytes ensheathing viable axons are likely to be of therapeutic significance. We report that leukemia inhibitory factor (LIF) can prevent oligodendrocyte apoptosis, notably contralateral to the spinal cord lesion, through the induction of the JAK/STAT and Akt signaling pathways as well as by potentiating the expression of the antiapoptotic molecule, cIAP2. Reduced oligodendrocyte apoptosis after SCI with LIF administration resulted in a substantial decrease in demyelination shown by the preservation of lamellated myelin surrounding viable axons and deposition of the degraded myelin basic protein. The data suggest that LIF signals survival in oligodendrocytes after SCI, prevents the secondary wave of demyelination, and thereby reduces inhibitory myelin deposits.

Item Type:	Refereed Article
Keywords:	cIAP2, Demyelination, Leukemia inhibitory factor
Research Division:	Biomedical and Clinical Sciences
Research Group:	Neurosciences
Research Field:	Neurosciences not elsewhere classified
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Small, DH (Professor David Small)
ID Code:	58534
Year Published:	2006
Web of Science® Times Cited:	53
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2009-10-13
Last Modified:	2009-10-13
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