Reduced Expression of Oligodendrocyte Linage-Enriched Transcripts During the Endoplasmic Reticulum Stress/Integrated Stress Response.

Endoplasmic reticulum (ER) stress in oligodendrocyte (OL) linage cells contributes to several CNS pathologies including traumatic spinal cord injury (SCI) and multiple sclerosis. Therefore, primary rat OL precursor cell (OPC) transcriptomes were analyzed using RNASeq after treatments with two ER stress-inducing drugs, thapsigargin (TG) or tunicamycin (TM). Gene ontology term (GO) enrichment showed that both drugs upregulated mRNAs associated with the general stress response.

Oligodendrocyte-selective deletion of the eIF2α kinase Perk/Eif2ak3 limits functional recovery after spinal cord injury.

After spinal cord injury (SCI), re-establishing cellular homeostasis is critical to optimize functional recovery. Central to that response is PERK signaling, which ultimately initiates a pro-apoptotic response if cellular homeostasis cannot be restored. Oligodendrocyte (OL) loss and white matter damage drive functional consequences and determine recovery potential after thoracic contusive SCI.

Enhanced oxidative phosphorylation, re-organized intracellular signaling, and epigenetic de-silencing as revealed by oligodendrocyte translatome analysis after contusive spinal cord injury.

Reducing the loss of oligodendrocytes (OLs) is a major goal for neuroprotection after spinal cord injury (SCI). Therefore, the OL translatome was determined in Ribotag:Plp1-CreERT2 mice at 2, 10, and 42 days after moderate contusive T9 SCI. At 2 and 42 days, mitochondrial respiration- or actin cytoskeleton/cell junction/cell adhesion mRNAs were upregulated or downregulated, respectively.

Enhanced oxidative phosphorylation, re-organized intracellular signaling, and epigenetic de-silencing as revealed by oligodendrocyte translatome analysis after contusive spinal cord injury.

Reducing the loss of oligodendrocytes (OLs) is a major goal for neuroprotection after spinal cord injury (SCI). Therefore, the OL translatome was determined in Ribotag:Plp1-CreERT2 mice at 2, 10, and 42 days after moderate contusive T9 SCI. At 2 and 42 days, mitochondrial respiration- or actin cytoskeleton/cell junction/cell adhesion mRNAs were upregulated or downregulated, respectively.

Opposite modulation of functional recovery following contusive spinal cord injury in mice with oligodendrocyte-selective deletions of Atf4 and Chop/Ddit3.

The integrated stress response (ISR)-activated transcription factors ATF4 and CHOP/DDIT3 may regulate oligodendrocyte (OL) survival, tissue damage and functional impairment/recovery in white matter pathologies, including traumatic spinal cord injury (SCI). Accordingly, in OLs of OL-specific RiboTag mice, Atf4, Chop/Ddit3 and their downstream target gene transcripts were acutely upregulated at 2, but not 10, days post-contusive T9 SCI coinciding with maximal loss of spinal cord tissue. Unexpectedly, another, OL-specific upregulation of Atf4/Chop followed at 42 days post-injury.

Acute Pharmacological Inhibition of Protein Kinase R-Like Endoplasmic Reticulum Kinase Signaling After Spinal Cord Injury Spares Oligodendrocytes and Improves Locomotor Recovery.

Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is a major signal transducer of the endoplasmic reticulum stress response (ERSR) pathway. Outcomes of PERK activation range from abrogating ER stress to induction of cell death, dependent on its level, duration, and cellular context. Current data demonstrate that after mouse spinal cord injury (SCI), acute inhibition of PERK (0-72 h) with the small molecule inhibitor GSK2656157 reduced ERSR while improving white matter sparing and hindlimb locomotion recovery.

The Proteostasis Network: A Global Therapeutic Target for Neuroprotection after Spinal Cord Injury.

Proteostasis (protein homeostasis) is critical for cellular as well as organismal survival. It is strictly regulated by multiple conserved pathways including the ubiquitin-proteasome system, autophagy, the heat shock response, the integrated stress response, and the unfolded protein response. These overlapping proteostasis maintenance modules respond to various forms of cellular stress as well as organismal injury.

Autophagy is essential for oligodendrocyte differentiation, survival, and proper myelination.

Deficient myelination, the spiral wrapping of highly specialized membrane around axons, causes severe neurological disorders. Maturation of oligodendrocyte progenitor cells (OPC) to myelinating oligodendrocytes (OL), the sole providers of central nervous system (CNS) myelin, is tightly regulated and involves extensive morphological changes. Here, we present evidence that autophagy, the targeted isolation of cytoplasm and organelles by the double-membrane autophagosome for lysosomal degradation, is essential for OPC/OL differentiation, survival, and proper myelin development.

The effect of adjunctive noncontact low frequency ultrasound on deep tissue pressure injury.

The optimal treatment for deep tissue pressure injuries has not been determined. Deep tissue pressure injuries represent a more ominous early stage pressure injury that may evolve into full thickness ulceration despite implementing the standard of care for pressure injury. A longitudinal prospective historical case control study design was used to determine the effectiveness of noncontact low frequency ultrasound plus standard of care (treatment group) in comparison to standard of care (control group) in reducing deep tissue pressure injury severity, total surface area, and final pressure injury stage.

Effects of non contact low-frequency ultrasound on healing of suspected deep tissue injury: a retrospective analysis.

The purpose of this study was to assess the effectiveness of non contact low-frequency ultrasound on the healing of suspected deep tissue injury (SDTI). Participants were adults ranging in age from 28 to 93 years old, with multiple diagnoses including anaemia, diabetes mellitus and hypertension. Data were examined retrospectively on 85 patients (intervention group = 43 and non intervention group = 42) with 127 SDTI (intervention group = 64 and non intervention group = 63).

Adjunctive use of noncontact low-frequency ultrasound for treatment of suspected deep tissue injury: a case series.

Purpose: We lack a clear understanding of the mechanisms of damage associated with suspected deep tissue injuries (SDTI) and sufficient evidence to determine the efficacy of various preventive interventions. The purpose of this article is to evaluate noncontact low-frequency ultrasound (NLFU) as one component of a preventive program designed for preventing SDTI from progressing to higher-stage pressure ulcers.

Cases: In March 2009, we added NLFU treatments daily for 5 days, then every other day until healed, to our prevention protocol in order to prevent progression of SDTI to a higher-stage pressure ulcer.