Focal phospholipases A2 group III injections induce cervical white matter injury and functional deficits with delayed recovery concomitant with Schwann cell remyelination

Phospholipases A2 (PLA2) are group of enzymes that hydrolyze membrane phospholipids at the sn-2 position. PLA2 are present in the brain and spinal cord and are implicated in several neurological disorders. Previously, we showed that PLA2 activity increases following traumatic spinal cord injury and injection of group III secretory PLA2 (sPLA2-III) demyelinates spinal cord axons. Here, we demonstrate that injections of sPLA2-III into the cervical dorsolateral funiculus (DLF) resulted in dose-dependent demyelination, loss of oligodendrocytes and astrocytes, as well as axonopathy. Additionally, spared axons within the lesion were remyelinated by Schwann cells between weeks 2 and 3. To assess functional loss and recovery, we employed a modified “Staircase Test” pellet retrieval device and footprint analysis of forelimb function during locomotion. Pellet retrieval assessment sensitively detected the dose dependent lesion and its recovery after sPLA2-III injections with greater sensitivity than footprint analysis. We believe that this is the first report of a reaching task being able to discriminate between various grades of cervical white matter damage and varying extents of recovery. Thus, our results indicate that sPLA2-III can create white matter pathologies that are remyelinated by Schwann cells 2 to 3 weeks after injury. Additionally, the pellet retrieval test is a sensitive and quantifiable method for assessing the dysfunction and later recovery mediated by sPLA2-III injections.