Investigation of vascular endothelial growth factor receptor-dependent neuroplasticity on rat nucleus tractus solitarius and phrenic nerve after chronic sustained hypoxia

Kuloglu N., BAŞARAN K. E., YAKAN B.

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, vol.35, no.12, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 35 Issue: 12
  • Publication Date: 2021
  • Doi Number: 10.1002/jbt.22918
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Food Science & Technology Abstracts, MEDLINE
  • Keywords: chronic sustained hypoxia, VEGFR-2, NTS, phrenic nerve, VENTILATORY RESPONSE, BRAIN-STEM, ACCLIMATIZATION, PLASTICITY, MICE
  • Erciyes University Affiliated: Yes


The neuronal system that controls respiration creates plasticity in response to physiological changes. Chronic sustained hypoxia causes neuroplasticity that contributes to ventilatory acclimatization to hypoxia (VAH). The purpose of this study is to explain the potential roles of the VAH mechanism developing because of chronic sustained hypoxia on respiratory neuroplasticity of vascular endothelial growth factor (VEGF) receptor activation on the nucleus tractus solitarius (NTS) and phrenic nerve. In this study 24 adult male Sprague-Dawley rats were used. Subjects were separated into four groups, a moderate-sham (mSHAM), severed-sham (sSHAM), moderate chronic sustained hypoxia (mCSH), and severed chronic sustained hypoxia (sCSH). Normoxic group (mSHAM and sSHAM) rats were exposed to 21% O-2 level (7 days) in the normobaric room while hypoxia group (mCSH and sCSH) rats were exposed to 13% and 10% O-2 level (7 days). Different protocols were applied for normoxic and hypoxia groups and ventilation, respiratory frequency, and tidal volume measurements were made with whole-body plethysmography. After the test HIF-1 alpha, erythropoietin (EPO), and VEGFR-2 expressions on the NTS region in the medulla oblongata and phrenic nerve motor neurons in spinal cord tissue were analyzed using the immunohistochemical stain method. Examinations on the medulla oblongata and spinal cord tissues revealed that HIF-1 alpha, EPO, and VEGFR-2 expressions increased in hypoxia groups compared to normoxic groups while a similar increase was also seen when respiratory parameters were assessed. Consequently, learning about VAH-related neuroplasticity mechanisms developed as a result of chronic continuous hypoxia will contribute to developing new therapeutical approaches to various diseases causing respiratory failure using brain plasticity without recourse to medicines.