End-to-side neurorrhaphy and lateral axonal sprouting in a long graft rat model.

OBJECTIVE/HYPOTHESIS: Controversy exists regarding collateral axonal sprouting across an end-to-side neurorrhaphy to provide functional motor reinnervation of a target organ without compromise of the donor nerve. Rat models may be limited in the study of end-to-side repair given potential contamination from the proximal nerve stump of the recipient distal nerve and the use of antagonistic muscle groups for donor and recipient. The current study attempts to address these issues by using a rat model in which an end-to-side coaptation is performed with a long graft interposed between the intact donor tibial nerve and the divided, distal contralateral tibial nerve. MATERIALS AND METHODS: The graft used in proximal end-to-side coaptation consisted of both sciatic nerves in a donor syngeneic animal. The distal repair to the contralateral tibial nerve was done immediately or in a delayed fashion to allow potential motor axons to transverse the graft before division of the recipient tibial nerve. RESULTS: After 24 weeks, axons were noted to transverse the entire distance of the graft and into the contralateral distal posterior tibial nerve. A significant increase in axonal numbers was observed in the immediate repairs compared with the delayed. No animal recovered functional motor ability on the contralateral side as assessed by walking tracks. CONCLUSIONS: These findings suggest the importance of immediate distal neurotrophic factors in encouraging nerve regeneration even in a long graft end-to-side repair. Our model is successful in demonstrating innervation through an end-to-side coaptation but questions its use given the lack of motor recovery.

Electron microscopy of colocalization of GABA and tyrosine hydroxylase expression in rat olfactory bulb transplants.

Juxtaglomerular (JG) neurons of rat olfactory bulb (OB) are a subset of inhibitory interneurons within the OB, acting via lateral inhibition to modulate the afferent input of the primary olfactory nerve. The JG neurons, composed of periglomerular, external tufted, and short axon cells, have been found to express various neurotransmitters, including gamma-amino butyric acid (GABA) and dopamine. A specific set of neurons within the periglomerular population have also been shown to coexpress these neurotransmitters. Deafferentation or functional odor deprivation of the normal OB causes a loss of tyrosine hydroxylase (TH) (the rate limiting enzyme in the dopamine synthesis pathway) expression within the JG cell population, but appears to have no effect on GABA levels. Our laboratory has developed a transplantation model to further study the effects of deafferentation and subsequent reinnervation within this system. Sections from transplant (TX) OBs were reacted for GABA and TH using immunocytochemical localization protocols and studied by electron microscopy. Numerous neuronal populations were found to be either TH or GABA positive in this study, with a specific subpopulation showing colocalization of both. Although the architecture of the TX OB is somewhat disrupted and the TH- and GABA-positive cells were not as uniform in their arrangement as they are in the normal OB, we found that these cells in the TX OB were morphologically similar to the JG cells of normal OB. Positively labeled profiles were also found to receive and form numerous synaptic contacts with both host olfactory nerve axons as well as with the processes of donor neurons. These synaptic contacts were within areas that resemble the glomeruli of normal OB, suggesting that lateral inhibition may occur within the TX OB as it does in the normal. The coexpression of GABA and TH within specific neurons also indicates that a unique population of JG neurons that occur in normal OB are also found within this transplanted system as well.