Research Article

Acute Putrescine Supplementation with Schwann Cell Implantation Improves Sensory and Serotonergic Axon Growth and Functional Recovery in Spinal Cord Injured Rats

Figure 1

The role of putrescine in neuron and Schwann cell responses. This figure summarizes the previously reported functions of polyamines in neurons and Schwann cells within the wider literature from in vitro and in vivo studies and how these mechanisms could elicit the observed responses in the current study. Neurotrophins and growth factors secreted by implanted Schwann can elevate intrinsic cyclic AMP levels within neurons. Cyclic AMP is an important second messenger whose main effectors are downstream protein kinase signaling cascades (e.g., PKA) that result in the phosphorylation and activation of the constitutive transcription factor CREB. Bound to the nuclear DNA, CREB is known to enhance the expression of a number of genes that include arginase 1, which encodes the first enzyme of the polyamine pathway to generate endogenous putrescine. Putrescine produces a number of neuroprotective effects by scavenging free radicals and suppressing excitotoxicity. Putrescine also promotes the reorganization of actin and microtubules, allowing axons to grow. Administered putrescine is known to be taken up by both the neuron, bolstering the effects of the endogenous polyamines, and SCs, encouraging their migration and proliferation in vitro. We hypothesize that SC implants and administered putrescine work in concert to augment each other’s ability to promote neuropreservation and neuroregeneration following SCI.