Tacrolimus (FK506) Increases Neuronal Expression of GAP-43 and Improves Functional Recovery after Spinal Cord Injury in Rats

Treatment with Immunosuppressants FTY720 and Tacrolimus Promotes Functional Recovery after Spinal Cord Injury in Rats

“…Tacrolimus (also called FK506), a kind of macrolides immune inhibitor, is widely used in organ transplantation (Fukudo et al 2009;Simmonds et al 2009). It can promote physiological functional recovery of transplanted allogeneic limbs (Dubernard et al 2003), and improve the locomotor function of limbs after SCI (Madsen et al 1998;Voda et al 2005;Pan et al 2006a) In the present study, it was also found that tacrolimus effected statistically significant improvements after SCI, as quantified by the BBB score, the inclined plane test, footprint analysis, electrophysiological tests and electron microscopic analysis. Like cyclosporin A, tacrolimus elicits immunosuppression by inhibiting the protein phosphatase 2B (calcineurin) and subsequently blocking activation of the nuclear factor of the activated T cell (NFAT), thereby preventing interleukin-2 (IL-2) transcription (Ahn et al 2007).…”

“…On the other hand, in vivo and in vitro studies have shown that many immune inhibitors, such as rapamycin toxin, cyclosporine A, and tacrolimus are helpful in the regeneration of central and peripheral axons (Shiraishi et al 2001;Gillon et al 2003). Tacrolimus can promote early physiological function recovery in transplanted allogeneic limbs (Dubernard et al 2003) and improve the limbs' locomotor function after acute SCI (Madsen et al 1998;Voda et al 2005;Pan et al 2006a). Tacrolimus has been considered as a potential therapy for SCI, since it has greater neuroprotective effects than that of methylprednisolone, a common drug used in the treatment of SCI (Kaymaz et al 2005;Lopez-Vales et al 2005).…”

Intrinsic Factors Contributing to Axon Regeneration in the Mammalian Nervous System

“…Application of the purine nucleoside inosine to goldfish neurons potentiates the expression of axonal growth genes and process outgrowth in vitro (Benowitz et al, 1998;Petrausch et al, 2000). Administration of this molecule to adult rats following unilateral corticospinal tract injury (Benowitz et al, 1999) or cortical ischemia (Chen et al, 2002) stimulates vigorous compensatory sprouting of intact axons, accompanied by some functional recovery.…”

“…To date, it is still unclear whether inosine may also promote regeneration of injured neurites. Improved regeneration, together with up-regulation of GAP-43, has been also obtained by administration of the immunosuppressant drug tacrolimus (FK-506), both in peripheral (Gold et al, 1995(Gold et al, , 1998 and in central neurons (Masden et al, 1998).…”

Drug development in spinal cord injury: What is the FDA looking for?

“…Neurorestorative agents enhance the inherent plasticity of surviving neurons. A number of agents have been identified-e.g., OP-1 (osteogenic protein 1), which stimulates dendritic branching and growth [50]; neuroimmunophilins, such as FK506 [51,52] and V-10,367 [53,54], which stimulate axonal sprouting and inhibitors of the myelin-derived Nogo protein, which acts to inhibit axonal growth [55]. Neuroprotective and neurorestorative agents also have potential applications in cell transplantation, where they could serve to protect transplanted cells and promote their differentiation and growth.…”