Neuroprotection in the peripheral nervous system

Hoke A. Neuroprtoection in the peripheral nervous system. Arch Neurol 2006; 63: 1681-1685

The authors criticise the dogma holding that there is a "dying back " neuropathy in which the axon degrades centripetally from the end. In other work (Griffin and Hoke) the concept of last field of irrigation is reversed, and neuronal body depends upon target derived growth factors for survival. Also, Raff et al proposed that the so-called dying back neuropathy is a programmed responsed similar to apoptosis. Neuroprotective activities designed for neuronal survival, such as in the brain or spinal cord, may be inappropos due to lack of significant neuronal death in many peripheral neuropathies. The author proposes research center on 2 areas: mechanisms involving distal axonal degeneration, and axon-glia mechanisms important for neuroprotection.

Unlike Wallerian degeneration, in many peripheral neuropathies there is compartmental degeneration of axons without physical compartmentalization. In HIV virus envelope gp120 involves chemokine receptors on Schwann cells. In familial ALS, mutations in the SOD 1 gene suggested initial ep abnormality was explained by axonal degeneration not neuronal loss.

In stroke literature ischemic preconditioning protects neurons and limits damage from future events. This endogenous protection may be related to astrocyte secreted erythropoietin. In sciatic transection in rats, Schwann cells in contact upregulate erythropoetin expression and DRG ensory neurons upregulate receptors for the same. The injury signal in nitric oxide, that activates hypoxia-inducible-factor 1 that induces erythropoetin changes. Exogenous erythropoietin helps in models of neuropathy due to paclitaxel, diabetic neuropathy, and cisplatinum induced PN.

The authors also note a mouse strain that is resistant to degeneration after injury, due to a Wlds gene (Wallerian degeneration-slow). Further studies of axon-glia interactions are needed.