Focal phospholipases A2 group III injections induce cervical white matter injury and functional deficits with delayed recovery concomitant with Schwann cell remyelination.
Phospholipases A(2) (PLA(2)) are group of enzymes that hydrolyze membrane phospholipids at the sn-2 position. PLA(2) are present in the brain and spinal cord and are implicated in several neurological disorders. Previously, we showed that PLA(2) activity increases following traumatic spinal cord injury and injection of group III secretory PLA(2) (sPLA(2)-III) demyelinates spinal cord axons. Here, we demonstrate that injections of sPLA(2)-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 sPLA(2)-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 sPLA(2)-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 sPLA(2)-III injections.
Kentucky Spinal Cord Injury Research Center, Departments of Neurological Surgery and Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, 511 S. Floyd Street, MDR 616, Louisville, KY 40292, USA.
W Lee
WL
Titsworth
Stephen M
SM
Onifer
Nai-Kui
NK
Liu
Xiao-Ming
XM
Xu
D000818:Animals; D001070:Appetitive Behavior; D001253:Astrocytes / Q000473:pathology; D001522:Behavior, Animal; D002574:Cervical Vertebrae; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005552:Forelimb / Q000503:physiopathology; D054520:Group III Phospholipases A2; D007278:Injections, Spinal; D008124:Locomotion; D009186:Myelin Sheath / Q000473:pathology; D009416:Nerve Regeneration; D009836:Oligodendroglia / Q000473:pathology; D010741:Phospholipases A / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012583:Schwann Cells / Q000473:pathology; D013118:Spinal Cord Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D013997:Time Factors
D010741:Phospholipases A; D054520:Group III Phospholipases A2; C083622:Pla2g3 protein, rat