Hypothermia treatment ameliorated cyclin-dependent kinase 5-mediated inflammation in ischemic stroke and improved outcomes in ischemic stroke patients

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DOI:

https://doi.org/10.6061/clinics/2019/e938

Keywords:

Hypothermia, Ischemic Stroke, CDK5, IL-1b, Inflammation

Abstract

OBJECTIVES: The inflammatory response is a key mechanism of neuronal damage and loss during acute ischemic stroke. Hypothermia has shown promise as a treatment for ischemic stroke. In this study, we investigated the molecular signaling pathways in ischemic stroke after hypothermia treatment. METHODS: Cyclin-dependent kinase 5 (CDK5) was overexpressed or silenced in cultured cells. Nuclear transcription factor-kB (NF-kB) activity was assessed by measurement of the luciferase reporter gene. An ischemic stroke model was established in Sprague–Dawley (SD) rats using the suture-occluded method. Animals were assigned to three groups: sham operation control, ischemic stroke, and ischemic stroke + hypothermia treatment groups. Interleukin 1b (IL-1b) levels in the culture supernatant and blood samples were assessed by ELISA. Protein expression was measured by Western blotting. RESULTS: In HEK293 cells and primary cortical neuronal cultures exposed to hypothermia, CDK5 overexpression was associated with increased IL-1b, caspase 1, and NF-kB levels. In both a murine model of stroke and in patients, increased IL-1b levels were observed after stroke, and hypothermia treatment was associated with lower IL-1b levels. Furthermore, hypothermia-treated patients showed significant improvement in neurophysiological functional outcome. CONCLUSIONS: Overall, hypothermia offers clinical benefit, most likely through its effects on the inflammatory response.

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Published

2019-10-29

How to Cite

Sun, H., Cai, J., Shen, S., & Ren, X. (2019). Hypothermia treatment ameliorated cyclin-dependent kinase 5-mediated inflammation in ischemic stroke and improved outcomes in ischemic stroke patients. Clinics, 74, e938. https://doi.org/10.6061/clinics/2019/e938

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Section

Original Articles