Nuclear expansion and pore opening are instant signs of neuronal hypoxia and can identify poorly fixed brains

Sci Rep. 2018 Oct 3;8(1):14770. doi: 10.1038/s41598-018-32878-1.

Abstract

The initial phase of neuronal death is not well characterized. Here, we show that expansion of the nuclear membrane without losing its integrity along with peripheralization of chromatin are immediate signs of neuronal injury. Importantly, these changes can be identified with commonly used nuclear stains and used as markers of poor perfusion-fixation. Although frozen sections are widely used, no markers are available to ensure that the observed changes were not confounded by perfusion-induced hypoxia/ischemia. Moreover, HMGB1 was immediately released and p53 translocated to mitochondria in hypoxic/ischemic neurons, whereas nuclear pore complex inhibitors prevented the nuclear changes, identifying novel neuroprotection targets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain / diagnostic imaging
  • Brain / pathology
  • Brain / ultrastructure*
  • Cell Death / genetics
  • Cell Nucleus / genetics
  • Cell Nucleus / pathology
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / ultrastructure
  • Chromatin / genetics
  • Corpus Callosum / diagnostic imaging
  • Corpus Callosum / ultrastructure
  • Disease Models, Animal
  • Glucose / genetics
  • HMGB1 Protein / genetics
  • Humans
  • Hypoxia-Ischemia, Brain / genetics*
  • Hypoxia-Ischemia, Brain / pathology
  • Mice
  • Microscopy, Electron, Scanning
  • Mitochondria / genetics
  • Mitochondria / pathology
  • Mitochondria / ultrastructure
  • Neurons / pathology
  • Neurons / ultrastructure*
  • Nuclear Envelope / pathology
  • Nuclear Envelope / ultrastructure*
  • Tissue Fixation / standards

Substances

  • Chromatin
  • HMGB1 Protein
  • Glucose