Retinal axon regeneration in peripheral nerve, tectal, and muscle grafts in adult rats

Abstract

This study examined whether prior regenerative growth through peripheral nerve (PN) bridging grafts influenced the specificity with which lesioned adult rat retinal ganglion cell (RGC) axons grew into co‐grafts of developing target tissue (fetal superior colliculus). Growth into nontarget (muscle) tissue was also examined. Autologous PN was grafted onto the transected optic nerve. After 14 days, the distal ends of the PNs were placed next to, or inserted into, embryonic tectal tissue or into autologous muscle grafts placed in frontal cortex cavities. Host retinal projections were examined 3–8 months later using anterograde and retrograde tracing techniques. In rats in which there was good apposition between PN and tectal tissue, small numbers of RGC axons were observed growing into the tectal grafts (maximum distance of 180 μm). No evidence of specific innervation of appropriate target regions within tectal grafts was detected, even though such regions (identified by acetylcholinesterase histochemistry) were often located close to the PN grafts. In rats with PN/muscle co‐grafts, the extent of retinal axon outgrowth was greater (up to 465 μm from the PN tip) and labelled profiles that resembled motor endplates were seen contacting muscle fibres. Previous studies have shown that spontaneously regenerating RGC axons consistently and selectively innervate appropriate target areas in fetal tectal tissue grafted directly into optic tract lesion cavities. Together, the data suggest that exposure to a PN environment may have reduced the extent of adult retinal axon growth into fetal tectal transplants and affected the way regenerating axons responded to specific developmental cues expressed by target cells in the co‐grafted tissue. J. Comp. Neurol. 412:617–632, 1999. © 1999 Wiley‐Liss, Inc.

Viral vector-mediated gene expression in olfactory ensheathing glia implants in the lesioned rat spinal cord

“…This is likely to be due to many factors, including the inhibitory environment of the CNS, scarring at the distal graft-host interface, 14 and the growth-promoting influence of the graft itself. 15 Over the past few years there has been increasing interest in using another glial cell type, the olfactory ensheathing glia (OEG) cell. 16 Under normal circumstances OEG guide new primary olfactory axons growing from the olfactory epithelium towards their targets, the olfactory bulb glomeruli, where they synapse on, for instance, the dendrites of mitral cells.…”

Migration of cells into and out of peripheral nerve isografts in the peripheral and central nervous systems of the adult mouse

“…Clinically, PN grafts are used to repair defects in human PN that are too large to allow direct re‐attachment of injured stumps (Millesi, 1991; Bain, 1998). In adult central nervous system (CNS), an environment not normally conducive to axon regeneration, experimental PN autografts have been used in animals to induce axon regrowth across brain and spinal cord injury sites (Bray & Aguayo, 1989; Cheng et al ., 1996; Tan & Harvey, 1999). Preliminary human trials have also been reported (Cheng, 2000).…”

Transplanted neurons form both normal and ectopic projections in the adult brain

“…It has been suggested that injury or lesions open up axonal or synaptic space and modify the expression of neuronal growth factors, and are required for transplanted or endogenously derived neurons to project through the adult brain (Macklis, 1993;Magavi et al, 2000;Singec and Snyder, 2007). Injury and the subsequent denervation induces changes in the target regions of the projections, the expression of factors important for neuronal survival and neurite outgrowth, and the number and types of microglia and astrocytes present in the brain (reviewed by Tan and Harvey, 1999). In the current experiments, embryonic LGE or cortical neurons transplanted into the striatum projected to distant subcortical targets even in the relative absence of injury, suggesting that permissive and guidance signals are present in the intact brain.…”