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1. Introduction
Nerve injury can occur at any point along the length of a peripheral nerve as it courses from the root through the plexus and then to the target organ. There are a number of mechanisms whereby peripheral nerves may be directly traumatized, including compression, traction, drug injection, and laceration, toxins, ischemia, infection, and physical agents. The principal target of peripheral nerve injury is the axon. Injury may also affect specialized neuronal sheath cells called Schwann cells (SCs), which are intimately associated with all peripheral nerve axons. Irrespective of cause, there is a limited range of responses to peripheral nerve injury of which the most important is Wallerian degeneration (WD).
WD is a sequential pattern of axonal degeneration, myelin degradation, and supporting glial cell proliferation lasting 24–48 h. During this complex process, various events take place, including blood-nerve barrier dysfunction, endoneural space reorganization [1], and most importantly for our purposes, the induction of an intense inflammatory response, constituted by inflammatory mediator release and production [2]. Axonal degeneration initiates this response, activating SC and macrophages, that prolipherate and activate, clearing myelin debris and producing cytokines that perpetuate an inflammatory state. Axonal regeneration is then regulated by the interactions between all the involved cell types and by cytokines, chemokines, growth factors, and other inflammatory mediators [2]. All these events culminate in the promotion of an environment suitable for subsequent regeneration, repair, and axon regrowth.
Arachidonic acid (AA) and its metabolites are known to modulate neuronal function and survival. There is also evidence that AA derivatives, such as prostaglandins (PG), leukotrienes, and the enzymes involved in their production, such as cyclooxygenases (COX), lipooxygenases (LOX), among others, are centrally involved in WD and in axonal regeneration [2]. In this paper we will discuss the available evidence that sheds light in this issue.
2. Phospholipases and AA
Phospholipases (PL) are ubiquitous in mammalian cells and serve to cleave free fatty acids from cell membrane phospholipids. AA is one such fatty acid, and itself a precursor for eicosanoids. PLs are known to be upregulated in neurons weeks after crush injury to...