A novel method for establishing daily in vivo concentration gradients of soluble nerve growth factor (NGF)

Despite the capacity for spontaneous axonal regeneration, recovery following injuries to the peripheral nervous system (PNS) following transection are often incomplete and limited to short distances. Nerve growth factor (NGF) has been previously shown to support neuron survival, and direct growth of both developing and regenerating nerve fibers along a concentration gradient, based largely on in vitro studies. Here, we present a novel in vivo model of administering daily concentration gradients of NGF by directly manipulating the placement of the catheter-nerve conduit junction. Our results show that a dose of 800 pg NGF can be reliably used to establish a chemotactic concentration gradient over both a transient time period, and chronically through repeated daily administrations of the drug. Results from these studies may lead to a better mechanistic understanding of how concentration gradients of soluble NGF influence in vivo peripheral nerve regeneration.