Fig. (3). Overview of sPLA₂’s role in spinal cord injury.

The toxicity of sPLA₂ is compounded by three factors. 1) sPLA₂ is upregulated by commonly known neurotoxic mechanisms such as oxidative stress, cytokines, and EAA. 2) Both the primary metabolites of sPLA₂ activity, such as free fatty acids and lysophospholipids, and the secondary metabolites, such as eicosanoids and platelet activating factor, are toxic to the CNS. 3) Finally, sPLA₂ has been shown to reciprocally upregulate oxidative stress, cytokines, and EAA thus propagating a positive feedback loop resulting in cytotoxicity and secondary SCI. It must also be noted that sPLA₂ does not work in isolation from cPLA₂ and iPLA₂, rather a reciprocal activity is often demonstrated among the PLA₂ subfamilies.