The effect of granulocyte colony-stimulating factor administration on carbon monoxide neurotoxicity in rats

Abstract

Granulocyte colony-stimulating factor (G-CSF) is considered to be a novel neuroprotective agent. Beneficial effects have been demonstrated by administrating G-CSF in different experimental stroke models. In this study, we evaluated the efficacy of G-CSF therapy on carbon monoxide (CO) neurotoxicity in rats exposed to acute CO poisoning. Immediately after exposure to 3,000 ppm of CO for 60 minutes, 50, 100, and 150 µg/kg of G-CSF or normal saline were administered to rats. Rats were sacrificed after 24 hours for serum marker analysis or 1 week for histopathological examination. Brain sections were stained with hematoxylin and eosin to assess leukocyte infiltration and hippocampal injury and with Luxol fast blue to assess demyelination. S100β and glial fibrillary acidic protein (GFAP) serum levels were evaluated by commercial enzyme-linked immunosorbent assay kits. According to histopathological findings, G-CSF administration significantly restricted white-matter demyelination (150 µg/kg) (P = 0.006). Also, serum levels of S100β in G-CSF-treated groups (100 and 150 µg/kg) decreased significantly (P < 0.01and P < 0.05, respectively). In all does, G-CSF significantly reduced serum levels of GFAP (P < 0.01 for 50 µg/kg and P < 0.001 for other doses). Administration of G-CSF after CO poisoning attenuates brain cell damage through remyelination. G-CSF also decreases levels of related biomarkers, such as S100β and GFAP.

Keywords::

• Carbon monoxide
• neurotoxicity
• granulocyte colony-stimulating factor

Acknowledgment

The authors thank the pathology laboratories at Ghaem Hospitals (Mashhad University of Medical Sciences) and the Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, for their kind assistance.

Declaration of interest

This study is part of a Ph.D. thesis and is supported by the affairs at Mashhad University of Medical Sciences.