Neural Regeneration Research (Jan 2020)

Mechanism of delayed encephalopathy after acute carbon monoxide poisoning

  • Yan-Qing Huang,
  • Zheng-Rong Peng,
  • Fang-Ling Huang,
  • A-Li Yang

DOI
https://doi.org/10.4103/1673-5374.284995
Journal volume & issue
Vol. 15, no. 12
pp. 2286 – 2295

Abstract

Read online

Many hypotheses exist regarding the mechanism underlying delayed encephalopathy after acute carbon monoxide poisoning (DEACMP), including the inflammation and immune-mediated damage hypothesis and the cellular apoptosis and direct neuronal toxicity hypothesis; however, no existing hypothesis provides a satisfactory explanation for the complex clinical processes observed in DEACMP. Leucine-rich repeat and immunoglobulin-like domain-containing protein-1 (LINGO-1) activates the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling pathway, which negatively regulates oligodendrocyte myelination, axonal growth, and neuronal survival, causing myelin damage and participating in the pathophysiological processes associated with many central nervous system diseases. However, whether LINGO-1 is involved in DEACMP remains unclear. A DEACMP model was established in rats by allowing them to inhale 1000 ppm carbon monoxide gas for 40 minutes, followed by 3000 ppm carbon monoxide gas for an additional 20 minutes. The results showed that compared with control rats, DEACMP rats showed significantly increased water maze latency and increased protein and mRNA expression levels of LINGO-1, RhoA, and ROCK2 in the brain. Compared with normal rats, significant increases in injured neurons in the hippocampus and myelin sheath damage in the lateral geniculate body were observed in DEACMP rats. From days 1 to 21 after DEACMP, the intraperitoneal injection of retinoic acid (10 mg/kg), which can inhibit LINGO-1 expression, was able to improve the above changes observed in the DEACMP model. Therefore, the overexpression of LINGO-1 appeared to increase following carbon monoxide poisoning, activating the RhoA/ROCK2 signaling pathway, which may be an important pathophysiological mechanism underlying DEACMP. This study was reviewed and approved by the Medical Ethics Committee of Xiangya Hospital of Central South Hospital (approval No. 201612684) on December 26, 2016.

Keywords