The role of H3K27 acetylation in oxygen-glucose deprivation-induced spinal cord injury and potential for neuroprotective therapies.

OBJECTIVE

Spinal cord injury (SCI) is a debilitating condition that often results in paralysis and lifelong medical challenges. Research has shown that epigenetic modifications, particularly histone acetylation, play a role in neuroprotection following hypoxic-ischemic events in SCI. The objective of this study was to explore the effects of histone H3K27 acetylation, along with its underlying mechanisms, on the tolerance to hypoxia and ischemia in SCI.

METHODS

This study employed an organotypic spinal cord slice culture model subjected to oxygen-glucose deprivation (OGD). We assessed cell apoptosis and changes in cellular type patterns under these conditions. Following hypoxia and ischemia, we analyzed the expression and distribution of H3K27ac across various nerve cell types. To identify key downstream genes, we integrated ChIP-seq and RNA-seq analyses, investigating molecular mechanisms driving the response to OGD in this model.

RESULTS

OGD stimulation increased cell apoptosis and induced time-dependent changes in the expression patterns of neurons, astrocytes, microglia, and oligodendrocytes in organotypic spinal cord slices, accompanied by a significant reduction in H3K27ac levels. Integrated ChIP-seq and RNA-seq analyses revealed that H3K27ac downregulation under hypoxic and ischemic conditions contributes to spinal cord damage by promoting neuroinflammation and disrupting gene regulation. Furthermore, we identified key downstream targets, including Apoc1, Spp1, Aff1, Brd4, KCNN3, and Rgma, which may represent promising therapeutic targets for SCI.

CONCLUSION

Our data underscore the pivotal role of H3K27ac in the organotypic spinal cord slice culture model following OGD exposure, offering promising avenues for neuroprotective therapies via epigenetic-immune regulation.