Alterations in the Local Axonal Environment Influence Target Reinnervation and Neuronal Survival After PostnataI Axotomy

Abstract

Abstract : Following peripheral nerve injury in adult animals, Schwann cells (SC) proliferate and provide guidance in the local axonal environment by generating the infrastructure along which regenerating nerves grow. A portion of the SC in the peripheral nerves of postnatal rats undergo apoptosis during normal development, and this apoptosis is augmented at the injury site and the neuromuscular junction (NMJ) following sciatic nerve axotomy. The current work determined that SC apoptosis occurs in the distal but not the proximal nerve segment after postnatal transection of the hypoglossal nerve, suggesting that SC apoptosis is a general, age-related and location-specific response to peripheral nerve injury. Apoptotic SC were found in two strategic locations for guiding axonal outgrowth during peripheral nerve regeneration: a) capping the transected end adjacent to the injury site and b) just proximal to the bifurcation of the nerve into medial and lateral branches. Electron microscopic (EM) analysis identified apoptotic and mitotic SC in close proximity within the distal nerve segment, supporting apoptosis and mitosisas closely related phenomena. Poor rates of neuronal survival and tongue musculature reinnervation following hypoglossal nerve transection in the postnatal rat may be related to the increased apoptosis of SC in the distal nerve segment after injury.