Nerve Regeneration through Nerve Autografts and Cold Preserved Allografts using Tacrolimus (FK506) in a Facial Paralysis Model: A Topographical and Neurophysiological Study in Monkeys

Abstract

The regeneration through nerve allografts temporarily treated with FK506 does not achieve the electrophysiological results and neuronal counts achieved with nerve autografts, but axonal collateralization in the allografts induces a similar activation of mimic muscles.

Administration of low-dose FK 506 accelerates histomorphometric regeneration and functional outcomes after allograft nerve repair in a rat model

“…Significant improvement in nerve regeneration rates could minimize denervation changes and improve longterm functional recovery from nerve injuries: the immunosuppressive drug FK 506 has been shown to have neuroprotective and neurotrophic actions in experimental models, increasing neurite elongation and accelerating the rate of nerve regeneration in vitro and in vivo (Lassner et al, 1989;Gold et al, 1995;Wang et al, 1997;Katsube et al, 1998;Doolabh and Mackinnon, 1999;Jost et al, 2000;Lee et al, 2000;Wang et al, 2002;Udina et al, 2002;Hontanilla et al, 2006). Thus, FK 506 could be useful, even clinically, for enhancing regeneration after surgical repair by improving the rate of axonal growth with allografts.…”

Correlation of three sciatic functional indices with histomorphometric findings in a rat sciatic nerve allograft repair model

“…This MBP-staining and sampling procedure does not substitute the traditional staining methods (e.g., toluidine blue, osmium tetroxide), which provide other type of information, e.g., count and size of axons and fibers. 20,[44][45][46] But it is not the total count or size of axons stained with different methods that determines the walking tracks, but the regeneration and firing of myelinated nerve fibers that innervate the muscle. [47][48][49] Hence, for histomorphological assessment in this study, it was feasible to use polyclonal antibodies with a high-affinity for marking only intact MBP of nerve fibers [50][51][52] and to choose randomly selected sampling grids as a nonbiased stereologic technique for quantitative morphological assessment avoiding sampling errors.…”

“…[13][14][15][16][17][18][19][20] Hence, FK 506 could potentially enhance regeneration after surgical nerve repair by improving the rate of axonal growth within transplanted allografts. There are several reports of positive results regarding nerve regeneration in animals and humans immunosuppressed by FK 506.…”

Experimental Video Analysis of Eye Blink Reflex in a Primate Model

“…However, the results of these methods do not always correlate with each other, making interpretation challenging (1,2,4,9,10). Although functional methods directly evaluate the success of neural regeneration, other types of assessments can provide only indirect evidence of regeneration (8,9,11).…”