Functional and Morphological Restoration of Intracranial Brachial Lesion of the Retinocollicular Pathway by Peripheral Nerve Autografts in Adult Hamsters

Abstract

Axons of adult mammals can regenerate through peripheral nerve grafts and restore the retinocollicular pathway if lesioned proximal to the retinal ganglion cell somata. Whether the grafting and subsequent reinnervation of the superior colliculus (SC) is possible in distal axotomy in the brain is a question of clinical relevance. We have deafferented the SC of adult hamsters at its brachium thus axotomizing the retinal ganglion cell axons rostral to its synaptic contact with the SC neurons. After unilateral brachium transection, a short segment of the autologous sciatic nerve was grafted to bridge the lesioned site to the SC (n=28). As controls the brachium was transected and left ungrafted (n=12). Functional restoration was examined 3 to 75 weeks later in grafted (n=16) and control (n=5) animals by recording visual evoked responses from the collicular cells. Prior to recording the grafts were visually evaluated and categorized into successfully (n=8) and unsuccessfully (n=8) grafted groups. To diffuse flash stimuli applied to the contralateral eye, visual evoked field potentials were recorded from all successfully grafted, but not in unsuccessfully grafted (with the exception of one animal) nor control animals. Unitary spike responses to diffuse flash stimuli were recorded exclusively from three successfully grafted animals. Morphological reinnervation was examined in the remaining grafted (n=12) and control (n=7) animals by anterogradely labeling the regenerating retinal axons with WGA-HRP. Axons in the grafts and their terminals in the superficial layers of the SC were clearly labeled in 8 of the grafted and none of the controls. From these results we conclude that the brachium of the SC is conducive to axonal regeneration and the peripheral nerve graft is indeed effective in restoring distally axotomized visual pathway in adult mammals.