Epigenetics of Neural Repair Following Spinal Cord Injury

Abstract

Spinal cord injury results from an insult inflicted on the spinal cord that usually encompasses its 4 major functions (motor, sensory, autonomic, and reflex). The type of deficits resulting from spinal cord injury arise from primary insult, but their long-term severity is due to a multitude of pathophysiological processes during the secondary phase of injury. The failure of the mammalian spinal cord to regenerate and repair is often attributed to the very feature that makes the central nervous system special-it becomes so highly specialized to perform higher functions that it cannot effectively reactivate developmental programs to re-build novel circuitry to restore function after injury. Added to this is an extensive gliotic and immune response that is essential for clearance of cellular debris, but also lays down many obstacles that are detrimental to regeneration. Here, we discuss how the mature chromatin state of different central nervous system cells (neural, glial, and immune) may contribute to secondary pathophysiology, and how restoring silenced developmental gene expression by altering histone acetylation could stall secondary damage and contribute to novel approaches to stimulate endogenous repair.

The Epigenetics of Stroke Recovery and Rehabilitation: From Polycomb to Histone Deacetylases

“…Acetylation of histone tails interdicts electrostatic interactions between histone proteins and DNA, and thus favors a more transcriptionally competent state [46,47]. As transcription appears to be required for neurite outgrowth, a reasonable model is that small molecules that bias histones toward an acetylated state [histone acetyltransferase activators (see article by Boutillier et al in this issue [48]) or HDAC inhibitors (see articles by Di Giovanni et al [49], Wagner et al [50], and Roskams et al [51] in this issue)] should enhance neurite outgrowth and stroke recovery. HDAC inhibitors are believed to bias gene expression toward the growth program via effects on nuclear and axonal HDACs.…”

Effect of TNF-α Inhibition on Bone Marrow-Derived Mesenchymal Stem Cells in Neurological Function Recovery after Spinal Cord Injury via the Wnt Signaling Pathway in a Rat Model

“…Although SCI treatment has always been a challenge for clinical practitioners and scientists, some progress has still been made, such as stem-cell-based therapies [5]. In addition, after SCI, the central nervous system fails to effectively reactivate developmental programs to rebuild novel circuitry to restore function [6]. Thus, it is vital to assess the functional state and to quantify the clinical neurological impairment of patients with traumatic SCI [7].…”

Recent advances in the pharmacologic treatment of spinal cord injury

“…More specifically, researchers have speculated that the mature chromatin status of the cells comprising the spinal cord may be blocking these cells from reactivating the developmental programs necessary to successfully rebuild the damaged tissue (York et al 2013). DNA methylation, chromatin structure, and histone acetylation status are the broad categories of epigenetic modifications that drive changes in gene expression.…”