Inter-relationships between angiogenesis and nerve regeneration: a histochemical study

Abstract

Whilst increases in capillary number and permeability occurring during nerve regeneration suggest an interaction between regenerating axons and blood vessels, clinical attempts to improve nerve regeneration by augmenting nerve graft vascularisation have produced conflicting results and the nature of their relationship remains obscure. A better understanding of the process might be exploited in the development of a synthetic alternative to the autologous nerve graft and bring an improvement in the clinical results of nerve repair. To clarify this relationship the growth of axons and blood vessels through mats of orientated fibronectin grafted in rat sciatic nerves was assessed morphologically. Fibronectin, which supports axonal regeneration, is initially acellular, ensuring all vascular and neural elements within the graft are newly formed. To follow the progression of the elements, grafts were harvested between 3 and 30 days and stained with antibodies against endothelial cells (RECA-1), Schwann cells (S-100) and axons (a polyclonal or monoclonal panaxonal marker). Dual fluorescence staining combined with double exposure photography allowed the simultaneous visualisation of these elements and the demonstration of their true relative positions. Graft vascularisation came initially from the adjacent muscle bed. A neovascularisation front preceded axonal regeneration, although vessel and axonal orientation appeared similar. Schwann cells and axons extended together, never exceeding the area of vascularisation and appeared most numerous in well vascularised areas containing longitudinally orientated vessels. These results suggest that provision of a well vascularised, longitudinally orientated conduit may enhance nerve regeneration.