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

W. Lee Titsworth, Stephen M. Onifer, Naikui Liu, Xiao-Ming Xu

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)150-162
Number of pages13
JournalExperimental Neurology
Volume207
Issue number1
DOIs
StatePublished - Sep 2007
Externally publishedYes

Fingerprint

Group III Phospholipases A2
Phospholipases A2
Schwann Cells
Injections
Axons
Spinal Cord
Wounds and Injuries
Spinal Injections
Forelimb
Oligodendroglia
Demyelinating Diseases
Locomotion
Nervous System Diseases
Spinal Cord Injuries
Astrocytes
Phospholipids
Pathology
Equipment and Supplies
Membranes
Brain

Keywords

  • Cervical
  • Demyelination
  • Dorsolateral funiculus
  • Pellet retrieval
  • Phospholipases A
  • Schwann cell
  • Secretory phospholipases A
  • Spinal cord

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

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title = "Focal phospholipases A2 group III injections induce cervical white matter injury and functional deficits with delayed recovery concomitant with Schwann cell remyelination",
abstract = "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.",
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T1 - Focal phospholipases A2 group III injections induce cervical white matter injury and functional deficits with delayed recovery concomitant with Schwann cell remyelination

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AU - Xu, Xiao-Ming

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N2 - 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.

AB - 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.

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