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-κB (NF-κB) 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 1β (IL-1β) 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-1β, caspase 1, and NF-κB levels. In both a murine model of stroke and in patients, increased IL-1β levels were observed after stroke, and hypothermia treatment was associated with lower IL-1β 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.
Highlights
Ischemic stroke is one of the leading causes of mortality worldwide and the number one cause of death in the northern area of China
Previous studies have shown that the serum interleukin 1b (IL-1b) level is elevated in ischemic stroke patients, indicating activation of the immune system, which is associated with infiltration of immune and inflammatory cells into the central nervous system, possibly mediating neuronal damage in the brain
We examined the correlation between Cyclin-dependent kinase 5 (CDK5) and Nuclear transcription factor-kB (NF-kB), a molecule known to mediate inflammatory responses
Summary
Inflammatory responses resulting from ischemic stroke have been recognized as a key factor in the pathology of ischemic stroke. Previous studies have shown that the serum interleukin 1b (IL-1b) level is elevated in ischemic stroke patients, indicating activation of the immune system, which is associated with infiltration of immune and inflammatory cells into the central nervous system, possibly mediating neuronal damage in the brain. Hypothermia is a promising treatment for stroke.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have