Association between CIRP expression and hypoxic‑ischemic brain injury in neonatal rats

Abstract

The role of cold inducible RNA-binding protein (CIRP) in mediating ischemic brain injury in neonatal rats under chronic hypobaric hypoxia was investigated. The neonatal rat model of chronic hypobaric hypoxia and the cell culture model of SH-SY5Y cells exposed to hypoxia (1% O 2 ) were constructed. The expression of CIRP and hypoxia-inducible factor-1α (HIF-1α) was detected after hypoxic exposure, and the apoptosis-related proteins were analyzed via terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and western blot analysis to detect neuronal apoptosis. Moreover, the effects of CIRP overexpression on HIF-1α and neuronal apoptosis were identified. Chronic hypobaric hypoxia can lead to HIF-1α expression and neuronal apoptosis in the body. CIRP was induced at early exposure (3 d/7 d). However, the CIRP level in the hypoxic group was obviously lower than that in the control group with the prolongation of exposure time (21 d). In addition, the knockdown of HIF-1α significantly reduced the neuronal apoptosis under hypoxic conditions, indicating that HIF-1α may promote apoptosis during exposure. The overexpression of CIRP significantly inhibited the upregulation of HIF-1α during hypoxia and the HIF-1α-mediated neuronal apoptosis. Results of the current study showed that, CIRP is involved in the ischemic brain injury induced by chronic hypoxia through downregulation of HIF-1α expression.

Extracellular CIRP Activates the IL-6Rα/STAT3/Cdk5 Pathway in Neurons

“…The neurodegeneration and dysfunction is essentially caused by the deregulation of multiple complex and diverse signal transduction pathways, many of which are required for normal regulated functions, which get abnormally triggered or repressed [31,32]. Studies from our and other labs have undoubtedly shown that eCIRP is a major contributing factor causing neuroin ammation, neuronal injury and memory dysfunction in various settings [7,8,9,10,33,34].…”

Extracellular CIRP Activates the IL-6Rα/STAT3/Cdk5 Pathway in Neurons

“…Studies from our and other labs have undoubtedly shown that eCIRP is a major contributing factor causing neuroin ammation, neuronal injury and memory dysfunction in various settings [7,8,9,10,33,34].…”

“…The neurodegeneration and dysfunction is essentially caused by the deregulation of multiple complex and diverse signal transduction pathways, many of which are required for normal regulated functions, which get abnormally triggered or repressed [31,32]. Studies from our and other labs have undoubtedly shown that eCIRP is a major contributing factor causing neuroin ammation, neuronal injury and memory dysfunction in various settings [7,8,9,10,33,34].…”